General, organic, and biological chemistry [5th ed] 9780547152813, 9780495831464, 0547152817, 0495831468

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General, Organic, and Biological Chemistry

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General, Organic, and Biological Chemistry F I F T H

E D I T I O N

H. STEPHEN STOKER Weber State University

Australia • Brazil • Japan • Korea • Mexico • Singapore • Spain • United Kingdom • United States

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General, Organic, and Biological Chemistry, Fifth Edition H. Stephen Stoker Acquisitions Editor: Kilean Kennedy Senior Development Editor: Rebecca Berardy Schwartz Associate Editor: Stephanie Van Camp

© 2010 Brooks/Cole, Cengage Learning ALL RIGHTS RESERVED. No part of this work covered by the copyright herein may be reproduced, transmitted, stored, or used in any form or by any means graphic, electronic, or mechanical, including but not limited to photocopying, recording, scanning, digitizing, taping, Web distribution, information networks, or information storage and retrieval systems, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without the prior written permission of the publisher.

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Brief Contents Preface PART I Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Chapter 7 Chapter 8 Chapter 9 Chapter 10 Chapter 11 PART II Chapter 12 Chapter 13 Chapter 14 Chapter 15 Chapter 16 Chapter 17 PART III Chapter 18 Chapter 19 Chapter 20 Chapter 21 Chapter 22 Chapter 23 Chapter 24 Chapter 25 Chapter 26

xiv

GENERAL CHEMISTRY Basic Concepts About Matter 1 Measurements in Chemistry 22 Atomic Structure and the Periodic Table 51 Chemical Bonding: The Ionic Bond Model 83 Chemical Bonding: The Covalent Bond Model 108 Chemical Calculations: Formula Masses, Moles, and Chemical Equations 137 Gases, Liquids and Solids 163 Solutions 192 Chemical Reactions 223 Acids, Bases, and Salts 253 Nuclear Chemistry 292

ORGANIC CHEMISTRY Saturated Hydrocarbons 321 Unsaturated Hydrocarbons 361 Alcohols, Phenols, and Ethers 399 Aldehydes and Ketones 442 Carboxylic Acids, Esters, and Other Acid Derivatives Amines and Amides 514

473

BIOLOGICAL CHEMISTRY Carbohydrates 555 Lipids 608 Proteins 655 Enzymes and Vitamins 698 Nucleic Acids 734 Biochemical Energy Production Carbohydrate Metabolism 811 Lipid Metabolism 842 Protein Metabolism 875

Answers to Selected Exercises Photo Credits A-26 Index/Glossary A-27

777

A-1

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Contents Preface

xiv

PA RT I GE N E RAL C H E MI STRY Chapter 1 Basic Concepts About Matter

1

1.1 Chemistry: The Study of Matter 1 1.2 Physical States of Matter 2 1.3 Properties of Matter 2 1.4 Changes in Matter 4 CHEMISTRY AT A GLANCE Use of the Terms Physical and Chemical 5 1.5 Pure Substances and Mixtures 6 1.6 Elements and Compounds 7 CHEMISTRY AT A GLANCE Classes of Matter 8 1.7 Discovery and Abundance of the Elements 9 1.8 Names and Chemical Symbols of the Elements 11 1.9 Atoms and Molecules 12 1.10 Chemical Formulas 15

CHEMICAL CONNECTIONS “Good” Versus “Bad” Properties for a Chemical Substance Elemental Composition of the Human Body 11

Chapter 2 Measurements in Chemistry 22 2.1 2.2 2.3 2.4

Measurement Systems 22 Metric System Units 23 Exact and Inexact Numbers 26 Uncertainty in Measurement and Significant Figures 26 CHEMISTRY AT A GLANCE Significant Figures 28 2.5 Significant Figures and Mathematical Operations 28 2.6 Scientific Notation 32 2.7 Conversion Factors 34 2.8 Dimensional Analysis 36 CHEMISTRY AT A GLANCE Conversion Factors 38 2.9 Density 39 2.10 Temperature Scales 41 2.11 Heat Energy and Specific Heat 43

CHEMICAL CONNECTIONS Body Density and Percent Body Fat 40 Normal Human Body Temperature 44

Chapter 3 Atomic Structure and the Periodic Table 51 3.1 Internal Structure of an Atom

51

3

3.2 Atomic Number and Mass Number 53 3.3 Isotopes and Atomic Masses 55 CHEMISTRY AT A GLANCE Atomic Structure 58 3.4 The Periodic Law and the Periodic Table 59 3.5 Metals and Nonmetals 62 3.6 Electron Arrangements Within Atoms 63 CHEMISTRY AT A GLANCE Shell–Subshell–Orbital 67 Interrelationships 3.7 Electron Configurations and Orbital Diagrams 67 3.8 The Electronic Basis for the Periodic Law and the Periodic Table 71 3.9 Classification of the Elements 73 CHEMISTRY AT A GLANCE Element Classification Schemes 75 and the Periodic Table

CHEMICAL CONNECTIONS Protium, Deuterium, and Tritium: The Three Isotopes of Hydrogen 55 Metallic Elements and the Human Body 64 Iron: The Most Abundant Transition Element in the Human Body 74

Chapter 4 Chemical Bonding: The Ionic Bond Model 83 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9

Chemical Bonds 83 Valence Electrons and Lewis Symbols 84 The Octet Rule 86 The Ionic Bond Model 87 The Sign and Magnitude of Ionic Charge 89 Lewis Structures for Ionic Compounds 91 Chemical Formulas for Ionic Compounds 92 The Structure of Ionic Compounds 93 Recognizing and Naming Binary Ionic Compounds 94 CHEMISTRY AT A GLANCE Ionic Bonds and Ionic 95 Compounds 4.10 Polyatomic Ions 98 4.11 Chemical Formulas and Names for Ionic Compounds Containing Polyatomic Ions 100 CHEMISTRY AT A GLANCE Nomenclature of Ionic Compounds 102

CHEMICAL CONNECTIONS Fresh Water, Seawater, Hard Water, and Soft Water: A Matter of Ions 90 Tooth Enamel: A Combination of Monatomic and Polyatomic Ions 100

Chapter 5 Chemical Bonding: The Covalent Bond Model 108 5.1 The Covalent Bond Model 108 5.2 Lewis Structures for Molecular Compounds

109

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5.3 Single, Double, and Triple Covalent Bonds 111 5.4 Valence Electrons and Number of Covalent Bonds Formed 112 5.5 Coordinate Covalent Bonds 113 5.6 Systematic Procedures for Drawing Lewis Structures 114 5.7 Bonding in Compounds with Polyatomic Ions Present 117 5.8 Molecular Geometry 118 CHEMISTRY AT A GLANCE The Geometry 121 of Molecules 5.9 Electronegativity 121 5.10 Bond Polarity 124 5.11 Molecular Polarity 126 CHEMISTRY AT A GLANCE Covalent Bonds and Molecular 127 Compounds 5.12 Naming Binary Molecular Compounds 130

7.11 Vapor Pressure of Liquids 177 7.12 Boiling and Boiling Point 180 7.13 Intermolecular Forces in Liquids 181 CHEMISTRY AT A GLANCE Intermolecular Forces

185

CHEMICAL CONNECTIONS The Importance of Gas Densities 167 Blood Pressure and the Sodium Ion/Potassium Ion Ratio Hydrogen Bonding and the Density of Water 184

178

CHEMICAL CONNECTIONS Nitric Oxide: A Molecule Whose Bonding Does Not Follow “The Rules” 117 The Chemical Senses of Smell and Taste 122

Chapter 6 Chemical Calculations: Formula Masses, Moles, and Chemical Equations 137 6.1 Formula Masses 137 6.2 The Mole: A Counting Unit for Chemists 138 6.3 The Mass of a Mole 140 6.4 Chemical Formulas and the Mole Concept 142 6.5 The Mole and Chemical Calculations 143 6.6 Writing and Balancing Chemical Equations 146 6.7 Chemical Equations and the Mole Concept 150 CHEMISTRY AT A GLANCE Relationships Involving the Mole 151 Concept 6.8 Chemical Calculations Using Chemical Equations 151

CHEMICAL CONNECTIONS Carbon Monoxide Air Pollution: A Case of Combining Ratios 153 Chemical Reactions on an Industrial Scale: Sulfuric Acid 156

Chapter 7 Gases, Liquids, and Solids 7.1 7.2 7.3 7.4 7.5

The Kinetic Molecular Theory of Matter 163 Kinetic Molecular Theory and Physical States Gas Law Variables 167 Boyle’s Law: A Pressure-Volume Relationship Charles’s Law: A Temperature-Volume Relationship 170 7.6 The Combined Gas Law 172 7.7 The Ideal Gas Law 172 7.8 Dalton’s Law of Partial Pressures 173 CHEMISTRY AT A GLANCE The Gas Laws 175 7.9 Changes of State 176 7.10 Evaporation of Liquids 177

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Contents

163 165 168

Chapter 8 Solutions

192

8.1 Characteristics of Solutions 192 8.2 Solubility 193 8.3 Solution Formation 196 8.4 Solubility Rules 197 8.5 Solution Concentration Units 198 8.6 Dilution 205 CHEMISTRY AT A GLANCE Solutions 207 8.7 Colloidal Dispersions and Suspensions 208 8.8 Colligative Properties of Solutions 209 8.9 Osmosis and Osmotic Pressure 210 CHEMISTRY AT A GLANCE Summary of Colligative Property 215 Terminology 8.10 Dialysis 215

CHEMICAL CONNECTIONS Factors Affecting Gas Solubility 195 Solubility of Vitamins 199 Controlled-Release Drugs: Regulating Concentration, Rate, and Location of Release 206 The Artificial Kidney: A Hemodialysis Machine 216

Chapter 9 Chemical Reactions 9.1 Types of Chemical Reactions 223 9.2 Redox and Nonredox Chemical Reactions CHEMISTRY AT A GLANCE Types of Chemical 228 Reactions

223 226

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9.3 Terminology Associated with Redox Processes 230 9.4 Collision Theory and Chemical Reactions 233 9.5 Exothermic and Endothermic Chemical Reactions 234 9.6 Factors That Influence Chemical Reaction Rates 235 9.7 Chemical Equilibrium 237 CHEMISTRY AT A GLANCE Factors That Increase Reaction 238 Rates 9.8 Equilibrium Constants 239 9.9 Altering Equilibrium Conditions: Le Châtelier’s Principle 243

CHEMICAL CONNECTIONS

CHEMICAL CONNECTIONS

Combustion Reactions, Carbon Dioxide, and Global Warming 227 “Undesirable” Oxidation–Reduction Processes: Metallic Corrosion 232 Stratospheric Ozone: An Equilibrium Situation 240

Chapter 10 Acids, Bases, and Salts

Tobacco Radioactivity and the Uranium-238 Decay Series Preserving Food Through Food Irradiation 307 The Indoor Radon-222 Problem 309

Excessive Acidity Within the Stomach: Antacids and Acid Inhibitors 265 Acid Rain: Excess Acidity 272 Blood Plasma pH and Hydrolysis 274 Buffering Action in Human Blood 279 Electrolytes and Body Fluids 283

Chapter 11 Nuclear Chemistry 11.1 Stable and Unstable Nuclides 292 11.2 The Nature of Radioactive Emissions

292 293

303

253

10.1 Arrhenius Acid–Base Theory 253 10.2 Brønsted–Lowry Acid–Base Theory 254 10.3 Mono-, Di-, and Triprotic Acids 257 CHEMISTRY AT A GLANCE Acid–Base Definitions 258 10.4 Strengths of Acids and Bases 258 10.5 Ionization Constants for Acids and Bases 260 10.6 Salts 261 10.7 Acid–Base Neutralization Chemical Reactions 262 10.8 Self-Ionization of Water 263 10.9 The pH Concept 266 10.10 The pKa Method for Expressing Acid Strength 269 10.11 The pH of Aqueous Salt Solutions 270 CHEMISTRY AT A GLANCE Acids and Acidic 271 Solutions 10.12 Buffers 274 10.13 The Henderson–Hasselbalch Equation 277 CHEMISTRY AT A GLANCE Buffer Systems 278 10.14 Electrolytes 278 10.15 Equivalents and Milliequivalents of Electrolytes 280 10.16 Acid–Base Titrations 282

CHEMICAL CONNECTIONS

11.3 Equations for Radioactive Decay 295 11.4 Rate of Radioactive Decay 297 CHEMISTRY AT A GLANCE Radioactive Decay 299 11.5 Transmutation and Bombardment Reactions 300 11.6 Radioactive Decay Series 302 11.7 Chemical Effects of Radiation 302 11.8 Biochemical Effects of Radiation 305 11.9 Detection of Radiation 306 11.10 Sources of Radiation Exposure 307 11.11 Nuclear Medicine 309 11.12 Nuclear Fission and Nuclear Fusion 312 CHEMISTRY AT A GLANCE Characteristics of Nuclear 315 Reactions 11.13 Nuclear and Chemical Reactions Compared 316

PA RT II O RGA NI C CHE MIST RY Chapter 12 Saturated Hydrocarbons

321

12.1 Organic and Inorganic Compounds 321 12.2 Bonding Characteristics of the Carbon Atom 322 12.3 Hydrocarbons and Hydrocarbon Derivatives 322 12.4 Alkanes: Acyclic Saturated Hydrocarbons 323 12.5 Structural Formulas 324 12.6 Alkane Isomerism 326 12.7 Conformations of Alkanes 327 12.8 IUPAC Nomenclature for Alkanes 329 12.9 Line-Angle Structural Formulas for Alkanes 335 CHEMISTRY AT A GLANCE Structural Representations for 338 Alkane Molecules 12.10 Classification of Carbon Atoms 338 12.11 Branched-Chain Alkyl Groups 339 12.12 Cycloalkanes 340 12.13 IUPAC Nomenclature for Cycloalkanes 341 12.14 Isomerism in Cycloalkanes 342 12.15 Sources of Alkanes and Cycloalkanes 344 12.16 Physical Properties of Alkanes and Cycloalkanes 346 12.17 Chemical Properties of Alkanes and Cycloalkanes 347 CHEMISTRY AT A GLANCE Properties of Alkanes 349 and Cycloalkanes 12.18 Nomenclature and Properties of Halogenated Alkanes 350

CHEMICAL CONNECTIONS The Occurrence of Methane 325 The Physiological Effects of Alkanes 348 Chlorofluorocarbons and the Ozone Layer 351

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Chapter 13 Unsaturated Hydrocarbons

361

13.1 Unsaturated Hydrocarbons 361 13.2 Characteristics of Alkenes and Cycloalkenes 362 13.3 IUPAC Nomenclature for Alkenes and Cycloalkenes 363 13.4 Line-Angle Structural Formulas for Alkenes 365 13.5 Constitutional Isomerism in Alkenes 366 13.6 Cis–Trans Isomerism in Alkenes 368 13.7 Naturally Occurring Alkenes 370 13.8 Physical Properties of Alkenes and Cycloalkenes 373 13.9 Chemical Reactions of Alkenes 373 13.10 Polymerization of Alkenes: Addition Polymers 378 13.11 Alkynes 382 CHEMISTRY AT A GLANCE Chemical Reactions 383 of Alkenes CHEMISTRY AT A GLANCE IUPAC Nomenclature for 384 Alkanes, Alkenes, and Alkynes 13.12 Aromatic Hydrocarbons 384 13.13 Names for Aromatic Hydrocarbons 386 13.14 Aromatic Hydrocarbons: Physical Properties and Sources 389 13.15 Chemical Reactions of Aromatic Hydrocarbons 390 13.16 Fused-Ring Aromatic Hydrocarbons 390

CHEMICAL CONNECTIONS Ethene: A Plant Hormone and High-Volume Industrial Chemical 367 Cis–Trans Isomerism and Vision 371 Carotenoids: A Source of Color 374 Fused-Ring Aromatic Hydrocarbons and Cancer 391

Chapter 14 Alcohols, Phenols, and Ethers 399 14.1 Bonding Characteristics of Oxygen Atoms in Organic Compounds 399 14.2 Structural Characteristics of Alcohols 400 14.3 Nomenclature for Alcohols 401 14.4 Isomerism for Alcohols 403 14.5 Important Commonly Encountered Alcohols 403 14.6 Physical Properties of Alcohols 407 14.7 Preparation of Alcohols 410 14.8 Classification of Alcohols 410 14.9 Chemical Reactions of Alcohols 411 CHEMISTRY AT A GLANCE Summary of Chemical Reactions 418 Involving Alcohols 14.10 Polymeric Alcohols 418 14.11 Structural Characteristics of Phenols 419 14.12 Nomenclature for Phenols 419 14.13 Physical and Chemical Properties of Phenols 420

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14.14 14.15 14.16 14.17 14.18 14.19 14.20 14.21

Occurrence of and Uses for Phenols 421 Structural Characteristics of Ethers 422 Nomenclature for Ethers 423 Isomerism for Ethers 426 Physical and Chemical Properties of Ethers Cyclic Ethers 428 Sulfur Analogs of Alcohols 429 Sulfur Analogs of Ethers 431

427

CHEMICAL CONNECTIONS Menthol: A Useful Naturally Occurring Terpene Alcohol 408 Ethers as General Anesthetics 425 Marijuana: The Most Commonly Used Illicit Drug 429 Garlic and Onions: Odiferous Medicinal Plants 432 CHEMISTRY AT A GLANCE Alcohols, Thiols, Ethers, 433 and Thioethers

Chapter 15 Aldehydes and Ketones

442

15.1 15.2 15.3 15.4 15.5 15.6 15.7 15.8 15.9 15.10

The Carbonyl Group 442 Compounds Containing a Carbonyl Group 443 The Aldehyde and Ketone Functional Groups 444 Nomenclature for Aldehydes 445 Nomenclature for Ketones 447 Isomerism for Aldehydes and Ketones 449 Selected Common Aldehydes and Ketones 450 Physical Properties of Aldehydes and Ketones 451 Preparation of Aldehydes and Ketones 453 Oxidation and Reduction of Aldehydes and Ketones 455 15.11 Reaction of Aldehydes and Ketones with Alcohols 458 CHEMISTRY AT A GLANCE Summary of Chemical Reactions 462 Involving Aldehydes and Ketones 15.12 Formaldehyde-Based Polymers 463 15.13 Sulfur-Containing Carbonyl Groups 464

CHEMICAL CONNECTIONS Lachrymatory Aldehydes and Ketones 449 Melanin: A Hair and Skin Pigment 452 Diabetes, Aldehyde Oxidation, and Glucose Testing 456

Chapter 16 Carboxylic Acids, Esters, and Other Acid Derivatives 473 16.1 Structure of Carboxylic Acids and Their Derivatives 473 16.2 IUPAC Nomenclature for Carboxylic Acids 474 16.3 Common Names for Carboxylic Acids 476 16.4 Polyfunctional Carboxylic Acids 479 16.5 Metabolic Carboxylic Acids 482 16.6 Physical Properties of Carboxylic Acids 483 16.7 Preparation of Carboxylic Acids 483 16.8 Acidity of Carboxylic Acids 484 16.9 Carboxylic Acid Salts 484

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16.10 Structure of Esters 487 16.11 Preparation of Esters 487 CHEMISTRY AT A GLANCE Summary of the “H Versus R” Relationship for Pairs of Hydrocarbon 488 Derivatives 16.12 Nomenclature for Esters 489 16.13 Selected Common Esters 491 16.14 Isomerism for Carboxylic Acids and Esters 493 16.15 Physical Properties of Esters 495 16.16 Chemical Reactions of Esters 495 16.17 Sulfur Analogs of Esters 497 CHEMISTRY AT A GLANCE Summary of Chemical Reactions 498 Involving Carboxylic Acids and Esters 16.18 Polyesters 499 16.19 Acid Chlorides and Acid Anhydrides 500 16.20 Esters and Anhydrides of Inorganic Acids 503

CHEMICAL CONNECTIONS Nonprescription Pain Relievers Derived from Propanoic Acid 480 Carboxylic Acids and Skin Care 481 Aspirin 494 Nitroglycerin: An Inorganic Triester 505

Chapter 17 Amines and Amides

514

17.1 Bonding Characteristics of Nitrogen Atoms in Organic Compounds 514 17.2 Structure and Classification of Amines 515 17.3 Nomenclature for Amines 516 17.4 Isomerism for Amines 518 17.5 Physical Properties of Amines 519 17.6 Basicity of Amines 519 17.7 Amine Salts 521 17.8 Preparation of Amines and Quaternary Ammonium Salts 523 17.9 Heterocyclic Amines 525 17.10 Selected Biochemically Important Amines 526 17.11 Alkaloids 529 17.12 Structure and Classification of Amides 532 17.13 Nomenclature for Amides 533 17.14 Selected Amides and Their Uses 535 17.15 Physical Properties of Amides 536 17.16 Preparation of Amides 537 17.17 Hydrolysis of Amides 540 17.18 Polyamides and Polyurethanes 542 CHEMISTRY AT A GLANCE Summary of Chemical Reactions 543 Involving Amines and Amides

CHEMICAL CONNECTIONS Caffeine: The Most Widely Used Central Nervous System Stimulant 526 Nicotine Addiction: A Widespread Example of Drug Dependence 527 Alkaloids Present in Chocolate 531 Acetaminophen: A Substituted Amide 538

PART III

B I O LO G I CA L CHE MIST RY

Chapter 18 Carbohydrates

555

18.1 18.2 18.3 18.4 18.5

Biochemistry—An Overview 555 Occurrence and Functions of Carbohydrates 556 Classification of Carbohydrates 557 Chirality: Handedness in Molecules 557 Stereoisomerism: Enantiomers and Diastereomers 560 18.6 Designating Handedness Using Fischer Projection Formulas 561 CHEMISTRY AT A GLANCE Constitutional Isomers and 566 Stereoisomers 18.7 Properties of Enantiomers 566 18.8 Classification of Monosaccharides 569 18.9 Biochemically Important Monosaccharides 570 18.10 Cyclic Forms of Monosaccharides 574 18.11 Haworth Projection Formulas 576 18.12 Reactions of Monosaccharides 577 18.13 Disaccharides 582 CHEMISTRY AT A GLANCE “Sugar Terminology” Associated 583 with Monosaccharides and Their Derivatives 18.14 General Characteristics of Polysaccharides 587 18.15 Storage Polysaccharides 591 18.16 Structural Polysaccharides 593 CHEMISTRY AT A GLANCE Types of Glycosidic Linkages for Common Glucose-Containing Di- and 595 Polysaccharides 18.17 Acidic Polysaccharides 595 18.18 Glycolipids and Glycoproteins: Cell Recognition 596 18.19 Dietary Considerations and Carbohydrates 597

CHEMICAL CONNECTIONS Blood Types and Monosaccharides 580 Lactose Intolerance and Galactosemia 585

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Changing Sugar Patterns: Decreased Sucrose, Increased Fructose 588 Artificial Sweeteners 590 “Good and Bad Carbs”: The Glycemic Index 597

Chapter 19 Lipids

608

19.1 Structure and Classification of Lipids 608 19.2 Types of Fatty Acids 609 19.3 Physical Properties of Fatty Acids 613 19.4 Energy-Storage Lipids: Triacylglycerols 614 19.5 Dietary Considerations and Triacylglycerols 618 19.6 Chemical Reactions of Triacylglycerols 621 CHEMISTRY AT A GLANCE Classification Schemes for Fatty 628 Acid Residues Present in Triacylglycerols 19.7 Membrane Lipids: Phospholipids 629 19.8 Membrane Lipids: Sphingoglycolipids 634 CHEMISTRY AT A GLANCE Terminology for and Structural Relationships Among Various Types of Fatty-Acid634 Containing Lipids 19.9 Membrane Lipids: Cholesterol 635 19.10 Cell Membranes 637 19.11 Emulsification Lipids: Bile Acids 640 19.12 Messenger Lipids: Steroid Hormones 641 19.13 Messenger Lipids: Eicosanoids 644 19.14 Protective-Coating Lipids: Biological Waxes 646 CHEMISTRY AT A GLANCE Types of Lipids in Terms of How 648 They Function

CHEMICAL CONNECTIONS The Fat Content of Tree Nuts and Peanuts 620 Artificial Fat Substitutes 624 The Cleansing Action of Soap 625 Trans Fatty Acids and Blood Cholesterol Levels 626 Steroid Drugs in Sports 644 The Mode of Action for Anti-Inflammatory Drugs 646

Chapter 20 Proteins

Contents

The Essential Amino Acids 658 Substitutes for Human Insulin 671 Protein Structure and the Color of Meat 682 Denaturation and Human Hair 686 Cyclosporine: An Antirejection Drug 688 Lipoproteins and Heart Disease Risk 690

Chapter 21 Enzymes and Vitamins

698

21.1 General Characteristics of Enzymes 698 21.2 Enzyme Structure 699 21.3 Nomenclature and Classification of Enzymes 699 21.4 Models of Enzyme Action 704 21.5 Enzyme Specificity 705 21.6 Factors That Affect Enzyme Activity 706 CHEMISTRY AT A GLANCE Enzyme Activity 709 21.7 Enzyme Inhibition 710 CHEMISTRY AT A GLANCE Enzyme Inhibition 712 21.8 Regulation of Enzyme Activity 713 21.9 Antibiotics That Inhibit Enzyme Activity 715 21.10 Medical Uses of Enzymes 718 21.11 General Characteristics of Vitamins 718 21.12 Water-Soluble Vitamins 721 21.13 Fat-Soluble Vitamins 725

CHEMICAL CONNECTIONS H. pylori and Stomach Ulcers 707 Enzymatic Browning: Discoloration of Fruits and Vegetables 708 Heart Attacks and Enzyme Analysis 719

655

20.1 Characteristics of Proteins 655 20.2 Amino Acids: The Building Blocks for Proteins 656 20.3 Chirality and Amino Acids 658 20.4 Acid–Base Properties of Amino Acids 659 20.5 Cysteine: A Chemically Unique Amino Acid 663 20.6 Peptides 663 20.7 Biochemically Important Small Peptides 667 20.8 General Structural Characteristics of Proteins 668 20.9 Primary Structure of Proteins 670 20.10 Secondary Structure of Proteins 671 20.11 Tertiary Structure of Proteins 674 20.12 Quaternary Structure of Proteins 677 20.13 Protein Classification Based on Shape 679 20.14 Protein Classification Based on Function 682 CHEMISTRY AT A GLANCE Protein Structure 678 20.15 Protein Hydrolysis 683 20.16 Protein Denaturation 684 20.17 Glycoproteins 685 20.18 Lipoproteins 689

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CHEMICAL CONNECTIONS

Chapter 22 Nucleic Acids

734

22.1 Types of Nucleic Acids 734 22.2 Nucleotides: Building Blocks of Nucleic Acids 22.3 Primary Nucleic Acid Structure 738 CHEMISTRY AT A GLANCE Nucleic Acid Structure 22.4 The DNA Double Helix 741 22.5 Replication of DNA Molecules 745

735 741

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22.6 Overview of Protein Synthesis 747 22.7 Ribonucleic Acids 747 CHEMISTRY AT A GLANCE DNA Replication 748 22.8 Transcription: RNA Synthesis 749 22.9 The Genetic Code 753 22.10 Anticodons and tRNA Molecules 756 22.11 Translation: Protein Synthesis 758 22.12 Mutations 763 22.13 Nucleic Acids and Viruses 763 CHEMISTRY AT A GLANCE Protein Synthesis: Transcription 764 and Translation 22.14 Recombinant DNA and Genetic Engineering 765 22.15 The Polymerase Chain Reaction 768 22.16 DNA Sequencing 769

CHEMICAL CONNECTIONS Lactate Accumulation 825 Diabetes Mellitus 836

Chapter 25 Lipid Metabolism

CHEMICAL CONNECTIONS Use of Synthetic Nucleic Acid Bases in Medicine 738 Antibiotics That Inhibit Bacterial Protein Synthesis 761

Chapter 23 Biochemical Energy Production 777 23.1 Metabolism 777 23.2 Metabolism and Cell Structure 779 23.3 Important Intermediate Compounds in Metabolic Pathways 781 23.4 High-Energy Phosphate Compounds 786 23.5 An Overview of Biochemical Energy Production 788 23.6 The Citric Acid Cycle 788 CHEMISTRY AT A GLANCE Simplified Summary of the Four 790 Stages of Biochemical Energy Production CHEMISTRY AT A GLANCE Summary of the Reactions of 794 the Citric Acid Cycle 23.7 The Electron Transport Chain 794 CHEMISTRY AT A GLANCE Summary of the Flow of Electrons Through the Four Complexes of the 799 Electron Transport Chain 23.8 Oxidative Phosphorylation 800 CHEMISTRY AT A GLANCE Summary of the Common 802 Metabolic Pathway 23.9 ATP Production for the Common Metabolic Pathway 802 23.10 The Importance of ATP 804 23.11 Non-ETC Oxygen-Consuming Reactions 804

CHEMICAL CONNECTIONS Cyanide Poisoning 801 Brown Fat, Newborn Babies, and Hibernating Animals 803 Flavonoids: An Important Class of Dietary Antioxidants 805

Chapter 24 Carbohydrate Metabolism

24.3 Fates of Pyruvate 822 24.4 ATP Production for the Complete Oxidation of Glucose 826 24.5 Glycogen Synthesis and Degradation 828 24.6 Gluconeogenesis 830 24.7 Terminology for Glucose Metabolic Pathways 832 24.8 The Pentose Phosphate Pathway 833 CHEMISTRY AT A GLANCE Glucose Metabolism 835 24.9 Hormonal Control of Carbohydrate Metabolism 835

811

24.1 Digestion and Absorption of Carbohydrates 24.2 Glycolysis 813

811

842

25.1 25.2 25.3 25.4 25.5 25.6 25.7 25.8

Digestion and Absorption of Lipids 842 Triacylglycerol Storage and Mobilization 845 Glycerol Metabolism 846 Oxidation of Fatty Acids 846 ATP Production from Fatty Acid Oxidation 851 Ketone Bodies 854 Biosynthesis of Fatty Acids: Lipogenesis 858 Relationships Between Lipogenesis and Citric Acid Cycle Intermediates 864 25.9 Biosynthesis of Cholesterol 864 CHEMISTRY AT A GLANCE Interrelationships Between 868 Carbohydrate and Lipid Metabolism 25.10 Relationships Between Lipid and Carbohydrate Metabolism 869

CHEMICAL CONNECTIONS High-Intensity Versus Low-Intensity Workouts 853 Statins: Drugs That Lower Plasma Levels of Cholesterol

Chapter 26 Protein Metabolism

867

875

26.1 Protein Digestion and Absorption 875 26.2 Amino Acid Utilization 877 26.3 Transamination and Oxidative Deamination 878 26.4 The Urea Cycle 883 26.5 Amino Acid Carbon Skeletons 888 26.6 Amino Acid Biosynthesis 891 26.7 Hemoglobin Catabolism 892 CHEMISTRY AT A GLANCE Interrelationships Among 895 Carbohydrate, Lipid, and Protein Metabolism 26.8 Interrelationships Among Metabolic Pathways 896

CHEMICAL CONNECTIONS The Chemical Composition of Urine 889 Arginine, Citrulline, and the Chemical Messenger Nitric Oxide Answers to Selected Exercises Photo Credits A-26 Index/Glossary A-27

889

A-1

Contents

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Preface

T

he positive responses of instructors and students who used the previous four editions of this text have been gratifying—and have lead to the new fifth edition that you hold in your hands. This new edition represents a renewed commitment to the goals I initially set out to meet when writing the first edition. These goals have not changed with the passage of time. My initial and still ongoing goals are to write a text in which 䊏 The needs are simultaneously met for the many students in the fields of nursing,

allied health, biological sciences, agricultural sciences, food sciences, and public health who are required to take such a course. 䊏 The development of chemical topics always starts out at ground level. The students who will use this text often have little or no background in chemistry and hence approach the course with a good deal of trepidation. This “ground level” approach addresses this situation. 䊏 The amount and level of mathematics is purposefully restricted. Clearly, some chemical principles cannot be divorced entirely from mathematics and, when this is the case, appropriate mathematical coverage is included. 䊏 The early chapters focus on fundamental chemical principles and the later chapters, built on these principles, develop the concepts and applications central to the fields of organic chemistry and biochemistry.

FOCUS

ON BIOCHEMISTRY Most students taking this course have a greater interest in the biochemistry portion of the course than the preceding two parts. But biochemistry, of course, cannot be understood without a knowledge of the fundamentals of organic chemistry, and understanding organic chemistry in turn depends on knowing the key concepts of general chemistry. Thus, in writing this text, I essentially started from the back and worked forward. I began by determining what topics would be considered in the biochemistry chapters and then tailored the organic and then general sections to support that presentation. Users of the previous editions confirm that this approach ensures an efficient but thorough coverage of the principles needed to understand biochemistry.

EMPHASIS ON VISUAL SUPPORT I believe strongly in visual reinforcement of key concepts in a textbook; thus, this book uses art and photos wherever possible to teach key concepts. Artwork is used to make connections and highlight what is important for the student to know. Reaction equations use color to emphasize the portions of a molecule that undergo change. Colors are likewise assigned to things like valence shells and classes of compounds to help students follow trends. Computer-generated, three-dimensional molecular models accompany many discussions in the organic and biochemistry sections of the text. Color photographs show applications of chemistry to help make concepts real and more readily remembered. Visual summary features, called Chemistry at a Glance, pull together material from several sections of a chapter to help students see the larger picture. For example, Chapter 3 features a Chemistry at a Glance on the shell–subshell–orbital interrelationships; Chapter 10 presents buffer solutions; Chapter 13 includes IUPAC nomenclature for alkanes, alkenes, and alkynes; and Chapter 22 summarizes DNA replication. The Chemistry at a Glance feature serves both as an overview for the student reading the material for the first time and as a review tool for the student preparing for exams. Given the popularity of

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the Chemistry at a Glance summaries in the previous editions, several new ones have been added and several existing ones have been updated or expanded. New topics selected for Chemistry at a Glance boxes include    

Acid–base definitions Structural representations for alkanes Structural characteristics and naming of alcohols, thiols, ethers, and thioethers Structural components of nucleic acids

COMMITMENT TO STUDENT LEARNING In addition to the study help Chemistry at a Glance offers, the text is built on a strong foundation of learning aids designed to help students master the course material.  Problem-solving pedagogy. Because problem solving is often difficult for students













in this course to master, I have taken special care to provide support to help students build their skills. Within the chapters, worked-out Examples follow the explanation of many concepts. These examples walk students through the thought processes involved in problem solving, carefully outlining all the steps involved. Each is immediately followed by a Practice Exercise, to reinforce the information just presented. Diversity of worked-out Examples. The number of worked-out Examples has been dramatically increased in this new edition, with most of the increase in the biochemistry chapters of the text. Worked-out Examples are a standard feature in the general chemistry portions of all textbooks for this market. This relates primarily to the mathematical nature of many general chemistry topics. In most texts, including earlier editions of this text, fewer worked-out Examples appear in the organic chemistry chapters and still fewer (almost none) in the biochemistry portion because of the mathematical demands decrease. This new edition changes that perspective. Thirtytwo new worked-out Examples are found within the biochemistry scope of the text. With the increasing detail that now accompanies biochemistry discussions about the human body, such Examples are warranted and can be very helpful for students. Chemical Connections. In every chapter Chemical Connections show chemistry as it appears in everyday life. These boxes focus on topics that are relevant to students’ future careers in the health and environmental fields and on those that are important for informed citizens to understand. Many of the health-related Chemical Connections have been updated to include the latest research findings, and include new boxes on metallic elements and the human body, iron (the most abundant transition element in the human body), carbon monoxide toxicity and the human body, the chemistry of nicotine addiction, and changing sugar consumption patterns (decreased sucrose, increased fructose). Margin notes. Liberally distributed throughout the text, margin notes provide tips for remembering and distinguishing between concepts, highlight links across chapters, and describe interesting historical background information. Defined terms. All definitions are highlighted in the text when they are first presented, using boldface and italic type. Each defined term appears as a complete sentence; students are never forced to deduce a definition from context. In addition, the definitions of all terms appear in the combined Index/Glossary found at the end of the text. A major emphasis in this new edition has been “refinements” in the defined terms arena. All defined terms were reexamined to see if they could be stated with greater clarity. The result was a “rewording” of many defined terms. Review aids. Several review aids appear at the ends of the chapters. Concepts to Remember and Key Reactions and Equations provide concise review of the material presented in the chapter. A Key Terms Review lists all the key terms in the chapter alphabetically and cross-references the section of the chapter in which they appear. These aids help students prepare for exams. End-of-chapter problems. An extensive set of end-of-chapter problems complements the worked examples within the chapters. Each end-of-chapter problem set is divided into two sections: Exercises and Problems and Additional Problems. The Exercises

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and Problems are organized by topic and paired, with each pair testing similar material and the answer to the odd-numbered member of the pair at the back of the book. These problems always involve only a single concept. The Additional Problems involve more than one concept and are more difficult than the Exercises and Problems. A new feature of this edition is the placement of 67 new “visual concept” problems in the general chemistry problem sets. This new problem type, which is integrated throughout the problem sets, is designed to facilitate learning through the use of molecular models, pictorial representations of chemical systems, graphs, and other visual portrayals.  Multiple-choice practice tests. Practice tests at the end of each chapter act as a cu-

mulative overview and self-study tool.

CONTENT CHANGES Coverage of a number of topics has been expanded in this edition. The two driving forces in expanded coverage considerations were (1) the requests of users and reviewers of the previous editions and (2) my desire to incorporate new research findings, particularly in the area of biochemistry, into the text. Topics with expanded coverage include                    

Percent composition by mass Colloidal dispersion and suspensions Equivalent and milliequivalent concentration units Nuclear stability Nuclear medicine Alkane–base polymers Cyclic esters (lactones) Polyester type polymers Acyl transfer reactions Amine salts Polyamide and polyurethane type polymers Protein isoelectric points Protein classification by molecular shape and by function Regulation of enzyme activity Ribosome structure Post-translational phase of protein synthesis Recombinant DNA technology Glycogenolysis Ketogeneis Lipogenesis

SUPPORTING MATERIALS 

For the Instructor

Supporting instructor materials are available to qualified adopters. Please consult your local Cengage Learning, Brooks/Cole representative for details. Visit www.cengage.com/ chemistry/stoker to    

See samples of materials Request a desk copy Locate your local representative Download electronic files of the Lab Manual Instructor’s Resource Manual and other helpful materials for instructors and students.

POWERLECTURE

WITH

DIPLOMA TESTING

AND

JOININTM INSTRUCTOR’S DVD.

PowerLecture (ISBN-10: 0-495-83160-3; ISBN-13: 978-0-495-83160-0) is a one-stop digital library and presentation tool that includes

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 Prepared Microsoft® PowerPoint® Lecture Slides that cover all key points from the



     

text in a convenient format with art and photographs. You can enhance the slides with your own materials or with additional interactive video and animations on the DVD for personalized, media-enhanced lectures. Image libraries in PowerPoint and JPEG formats that contain electronic files for all text art, most photographs, and all numbered tables in the text. These files can be used to create your own transparencies or PowerPoint lectures. JoinIn “clicker” Slides written specifically for the use of Chemistry with the classroom response system of your choice that allows you to seamlessly display student answers. The Complete Solutions Manual (H. Stephen Stoker), which contains answers to all end-of-chapter exercises. Sample chapters from the Study Guide with Solutions to Selected Problems. The Instructor’s Resource Guide for the textbook and for Experimental Chemistry. The Test Bank in printable Word and PDF documents, which provide an easy way to view all questions and answers from Diploma® Testing. Diploma® Testing, which combines a flexible test-editing program with comprehensive gradebook functions for easy administration and tracking. With Diploma Testing, instructors can administer tests via print, network server, or the Web. Questions can be selected based on their chapter/section, level of difficulty, question format, algorithmic functionality, topic, learning objective, and five levels of key words. With Diploma® Testing you can Choose from the 2,500 test items designed to measure the concepts and principles covered in the text. Ensure that each student gets a different version of the problem by selecting from preprogrammed algorithmic questions. Edit or author algorithmic or static questions that integrate into the existing bank, becoming part of the question database for future use. Choose problems designated as single-skill (easy), multi-skill (medium), and challenging and multi-skill (hard). Customize tests to assess the specific content from the text.

 Create several forms of the same test where questions and answers are scrambled.

OWL: ONLINE WEB-BASED LEARNING OWL is authored by Roberta Day, Beatrice Botch, and David Gross of the University of Massachusetts, Amherst; William Vining of the State University of New York at Oneonta; and Susan Young of Hartwick College: OWL Instant Access (two semesters): ISBN-10: 0-495-11105-8; ISBN-13:978-0495-11105-4 Instant Access to OWL e-Book (two semesters): ISBN-10: 0-495-83162-X; ISBN-13: 978-0-495-83162-4 Developed at the University of Massachusetts, Amherst, and class tested by tens of thousands of chemistry students, OWL is a fully customizable and flexible web-based learning system. OWL supports mastery learning and offers numerical, chemical, and contextual parameterization to produce thousands of problems correlated to this text. The OWL system also features a database of simulations, tutorials, and exercises, as well as end-of-chapter problems from the text. With OWL, you get the most widely used online learning system available for chemistry with unsurpassed reliability and dedicated training and support. The optional e-Book in OWL includes the complete electronic version of the text, fully integrated and linked to OWL homework problems. Most e-books in OWL are interactive and offer highlighting, notetaking, and bookmarking features that can all be saved. To view an OWL demo and for more information, visit www.cengage.com/owl or contact your Cengage Learning, Brooks/Cole representative.

LAB MANUAL INSTRUCTORS RESOURCE MANUAL Available on PowerLecture DVD and on the instructor companion site, this guide, by G. Lynn Carlson, Senior Lecturer

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Preface

Emeritus University of Wisconsin-Parkside, includes additional information related to the experiments in the Lab Manual. Additional safety notes, references, and web resources enhance the experience of the Lab for both the instructor and the students.

CENGAGE LEARNING CUSTOM SOLUTIONS

This allows you to develop personalized text solutions to meet your course needs. Match your learning materials to your syllabus and create the perfect learning solution—your customized text will contain the same thought-provoking, scientifically sound content, superior authorship, and stunning art that you’ve come to expect from Cengage Learning, Brooks/Cole texts, yet in a more flexible format. Visit www.cengage.com/custom.com to start building your book today.



For the Student

Visit the student website at www.cengage.com/chemistry/stoker to see samples of select student supplements. Students can purchase any Cengage Learning product at your local college store or at our preferred online store www.ichapters.com.

STUDENT COMPANION WEBSITE Accessible from www.cengage.com/chemistry/ stoker, this site provides online study tools including practice tests, flashcards, and Careers in Chemistry. OWL FOR GENERAL, ORGANIC, AND BIOLOGICAL CHEMISTRY See the above description in the instructor support materials section.

STUDY GUIDE

WITH SOLUTIONS TO SELECTED PROBLEMS By Danny V. White of American River College and Joanne A. White, this useful resource (ISBN: 0-547-16808-X; ISBN 13: 978-0-547-16808-1) will reinforce your skills with activities and practice problems for each chapter. After completing the end-of-chapter exercises, you’ll be able to check your answers for the odd-numbered questions.

LAB MANUAL The Lab Manual (ISBN-10: 0-547-16793-8; ISBN-13: 978-0-54716793-0) to accompany this textbook, by G. Lynn Carlson, Senior Lecturer Emeritus University of Wisconsin-Parkside, includes 42 experiments that were selected to match the topics in your textbook. Each experiment has an introduction, a procedure, a page of pre-lab exercises about the concepts the lab illustrates, and a report form. Some have a scenario that places the experiment in a real-world context. In addition, each experiment has a link to a set of references and on-line resources that might help you succeed with the experiment. ESSENTIAL ALGEBRA FOR CHEMISTRY STUDENTS, SECOND EDITION This short book by David W. Ball, Cleveland State University (ISBN-10: 0-495-01327-7; ISBN-13 978-0495-01327-3) is intended for students who lack confidence or competency in their essential mathematics skills necessary to survive in general chemistry. Each chapter focuses on a specific type of skill and has worked-out examples to show how these skills translate to chemical problem solving. It includes references to OWL, our web-based tutorial program that offers students access to online algebra skills exercises. SURVIVAL GUIDE FOR GENERAL CHEMISTRY WITH MATH REVIEW AND PROFICIENCY QUESTIONS, SECOND EDITION Intended to help you practice for exams, this survival guide by Charles H. Atwood, University of Georgia (ISBN-10: 0-495-38751-7; ISBN-13 978-0-495-38751-0) shows you how to solve difficult problems by dissecting them into manageable chunks. The guide includes three levels of proficiency questions—A, B, and minimal—to quickly build confidence as you master the knowledge you need to succeed in your course.

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Preface



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For the Laboratory

CENGAGE LEARNING, BROOKS/COLE LAB MANUALS

We offer a variety of printed manuals to meet all your general chemistry laboratory needs. Instructors can visit the chemistry site at www.cengage.com/chemistry for a full listing and description of these laboratory manuals and laboratory notebooks. All Cengage Learning lab manuals can be customized for your specific needs.

SIGNATURE LABS . . . FOR THE CUSTOMIZED LABORATORY Signature Labs combines the resources of Brooks/Cole, CER, and OuterNet Publishing to provide you unparalleled service in creating your ideal customized lab program. Select the experiments and artwork you need from our collection of content and imagery to find the perfect labs to match your course. Visit www.signaturelabs.com or contact your Cengage Learning representative for more information.

ACKNOWLEDGMENTS I would like to gratefully acknowledge the helpful comments of reviewers. 

Reviewers of the Fifth Edition

Teresa Brown, Rochester Community and Technical College; Karen Frindell, Santa Rosa Junior College; Irene Gerow, East Carolina University; Kevin Gratton, Johnson County Community College; Sherell Hickman, Brevard Community College; Martina Kaledin, Kennesaw State University; Allen W. Leung, Rio Hondo Community College; Michael J. Muhitch, Rochester University; Anthony Oertling, Eastern Washington University; James R. Paulson, University of Wisconsin—Oshkosh; Paul Sampson, Kent State University; Heather Sklenicka, Rochester Community and Technical College; Bobby Stanton, University of Georgia; Richard B. Triplett, Des Moines Area Community College; David A. Tramontozzi, Macomb Community College; Paolos Yohannes, Georgia Perimeter College. 

Reviewers of the Fourth Edition

Jennifer Adamski, Old Dominion University; M. Reza Asdjodi, University of Wisconsin— Eau Claire; Irene Gerow, East Carolina University; Ernest Kho, University of Hawaii at Hilo; Larry L. Land, University of Florida; Michael Myers, California State University— Long Beach; H. A. Peoples, Las Positas College; Shashi Rishi, Greenville Technical College; Steven M. Socol, McHenry County College. Special thanks go to Richard B. Triplett, Des Moines Area Community College; David Vanderlinden, Des Moines Area Community College; Barry Ganong, Mansfield University; and Michelle B. Moore, Weber State University for their help in ensuring this book’s accuracy. Thanks to Richard Gurney, Simmons College, for his contribution of PowerPoint Lecture Outline content. I also give special thanks to the people at Brooks/Cole, Cengage Learning, who guided the revision through various stages of development and production: Charles Hartford, Publisher, Chemistry; Senior Development Editor, Rebecca Berardy Schwartz; Andrea Cava, Project Editor; Naomi Kornhauser, Photo Researcher; and Stephanie VanCamp, Associate Editor. H. Stephen Stoker Weber State University

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A GUIDE TO General, Organic, and Biological Chemistry, Fifth Edition 2880T_ch16_473-513.indd Page 504 10/19/08 10:59:22 AM user-s131 /Volumes/MHSF/MH-SANFRAN/MHSF027/MHS...

EMPHASIS ON VISUAL SUPPORT Visual reinforcement is integral to the approach of this textbook. Art and photos are used whenever possible to teach key concepts.

Chloride ion

Artwork is used to make connections between macroscale and microscale phenomena.

Chloride ion

Sodium ion

16.20

Sodium ion

(a)

(b)

(c)

Figure 4.4 (a, b) A two-dimensional cross-section and a three-dimensional view of sodium chloride (NaCl), an ionic solid. Both views show an alternating array of positive and negative ions. (c) Sodium chloride crystals.

y O B HOO S OOH ⫹ CH3 OOH B O

O B HOO S OOO CH3 ⫹ H2O B O

Reaction equations use color to emphasize the portions of a molecule that undergo change.

Methyl ester of sulfuric acid

Sulfuric acid (H2SO4)

O B HOO P OOH ⫹ CH3 OOH A OH

O B HOO P OOO CH3 ⫹ H2O A OH

Phosphoric acid (H3PO4)

In the same manner that carboxylic acids are acidic (Section 16.8), phosphoric acid, diphosphoric acid, and triphosphoric acid are also acidic. The phosphoric acids are, however, polyprotic rather than monoprotic acids. The hydrogen atom in each of the —OH groups possesses acidic properties. All three phosphoric acids undergo esterification reactions with alcohols, producing species such as

Methyl ester of phosphoric acid

O B NOOH ⫹ CH3 OOH A O

O B NOOO CH3 ⫹ H2O A O

Nitric acid (HNO3)

Methyl ester of nitric acid

O O B B ROOO P OOO P OOH A A OH OH Diphosphate monoester

and

O O O B B B ROOO P OOO P OOO P OOH A A A OH OH OH Triphosphate monoester

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Carbohydrate Metabolism Chapter Outline 24.1 Digestion and Absorption of Carbohydrates 811 24.2 Glycolysis 813

24

Color is often used to highlight differences between related structures.

24.3 Fates of Pyruvate 822 24.4 ATP Production for the Complete Oxidation of Glucose 826 24.5 Glycogen Synthesis and Degradation 828 24.6 Gluconeogenesis 830 24.7 Terminology for Glucose Metabolic Pathways 832 24.8 The Pentose Phosphate Pathway 833

CHEMISTRY AT A GLANCE: Glucose Metabolism 835 24.9 Hormonal Control of Carbohydrate Metabolism 835

CHEMICAL CONNECTIONS

Carbohydrates are the major energy source for human beings.

Lactate Accumulation 825 Diabetes Mellitus 836

I

n this chapter we explore the relationship between carbohydrate metabolism and energy production in cells. The molecule glucose is the focal point of carbohydrate metabolism. Commonly called blood sugar, glucose is supplied to the body via the circulatory system and, after being absorbed by a cell, can be either oxidized to yield energy or stored as glycogen for future use. When sufficient oxygen is present, glucose is totally oxidized to CO2 and H2O. However, in the absence of oxygen, glucose is only partially oxidized to lactic acid. Besides supplying energy needs, glucose and other sixcarbon sugars can be converted into a variety of different sugars (C3, C4, C5, and C7) needed for biosynthesis. Some of the oxidative steps in carbohydrate metabolism also produce NADH and NADPH, sources of reductive power in cells.

Throughout the text, an exciting photo program helps students see the everyday applications of the chemistry they are learning.

24.1

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CHEMISTRY AT GLANCE Chemistry at a Glance diagrams demonstrate interrelationships among concepts. 2880T_ch08_192-222.indd Page 215 10/19/08 11:01:24 AM user-s131 /Volumes/MHSF/MH-SANFRAN/MHSF027/MHS...

Chemistry at a Glance pulls together material from a group of sections or a whole chapter to help students see the larger picture through a visual summary.

Summary of Colligative Property Terminology COLLIGATIVE PROPERTIES OF SOLUTIONS The physical properties of a solution that depend only on the concentration of solute particles in a given quantity of solute, not on the chemical identity of the particles.

VAPOR-PRESSURE LOWERING

BOILING-POINT ELEVATION

FREEZING-POINT DEPRESSION

OSMOTIC PRESSURE

Addition of a nonvolatile solute to a solvent makes the vapor pressure of the solution LOWER than that of the solvent alone.

Addition of a nonvolatile solute to a solvent makes the boiling point of the solution HIGHER than that of the solvent alone.

Addition of a nonvolatile solute to a solvent makes the freezing point of the solution LOWER than that of the solvent alone.

The pressure required to stop the net flow of water across a semipermeable membrane separating solutions of differing composition. OSMOLARITY Osmolarity = molarity × i, where i = number of particles from the dissociation of one formula unit of solute.

HYPOTONIC SOLUTION

HYPERTONIC SOLUTION

ISOTONIC SOLUTION

Solution with an osmotic pressure LOWER than that in cells. Causes cells to hemolyze (burst).

Solution with an osmotic pressure HIGHER than that in cells. Causes cells to crenate (shrink).

Solution with an osmotic pressure EQUAL to that in cells. Has no effect on cell size.

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Types of Chemical Reactions COMBINATION REACTION +

Y

X Y

X Y

2Al

+

3I2

2AlI3

2HgO

Aluminum reacts with iodine to form aluminum iodide.

SINGLE-REPLACEMENT REACTION

+

Y

2Hg +

O2

X

Mercury(II) oxide decomposes to form mercury and oxygen.

DOUBLE-REPLACEMENT REACTION

X

+

Y Z

Y

+

X Z

A X

+

B Y

A Y

+

Zn

+

CuSO4

Cu

+

ZnSO4

AgNO3 +

NaCl

AgCl

+ NaNO3

Zinc reacts with copper(II) sulfate to form copper and zinc sulfate.

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DECOMPOSITION REACTION

X

B X

Silver nitrate reacts with sodium chloride to form silver chloride and sodium nitrate.

Many Chemistry at a Glance features have been revised and several new ones have been added.

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CONNECTING TO CHEMISTRY In addition to Chemistry at a Glance, the text is built on a strong foundation of learning aids designed to help students master the course material.

c

HEMICAL

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onnections

Small amounts of nine transition metals are necessary for the proper functioning of the human body. They include all of the Period 4 transition metals except scandium and titanium plus the Period 5 transition metal molybdenum, as shown in the following transition metal portion of the periodic table. Transition Metals Period 4 Period 5 Period 6

V Cr Mn Fe Co Ni Cu Zn Mo

Iron is the most abundant, from a biochemical standpoint, of these transition metals; zinc is the second most abundant. Most of the body’s iron is found as a component of the proteins hemoglobin and myoglobin, where it functions in the transport and storage of oxygen. Hemoglobin is the oxygen carrier in red blood cells, and myoglobin stores oxygen in muscle cells. Iron-deficient blood has less oxygen-carrying capacity and often cannot completely meet the body’s energy needs. Energy deficiency—tiredness and apathy—is one of the symptoms of iron deficiency. Iron deficiency is a worldwide problem. Millions of people are unknowingly deficient. Even in the United States and Canada, about 20% of women and 3% of men have this problem; some 8% of women and 1% of men are anemic, experiencing fatigue, weakness, apathy, and headaches. Iron content of food derived from animal flesh

40% Heme iron

Chemical Connections boxes show chemistry as it appears in everyday life. Topics are relevant to students' future careers in the health and environmental fields and are important for informed citizens to understand.

Inadequate intake of iron, either from malnutrition or from high consumption of the wrong foods, is the usual cause of iron deficiency. In the Western world, the cause is often displacement of iron-rich foods by foods high in sugar and fat. About 80% of the iron in the body is in the blood, so iron losses are greatest whenever blood is lost. Blood loss from menstruation makes a woman’s need for iron nearly twice as great as a man’s. Also, women usually consume less food than men do. These two factors—lower intake and higher loss— cause iron deficiency to be likelier in women than in men. The iron RDA (recommended dietary allowance) is 8 mg per day for adult males and older women. For women of childbearing age, the RDA is 18 mg. This amount is necessary to replace menstrual loss and to provide the extra iron needed during pregnancy. Iron deficiency may also be caused by poor absorption of ingested iron. A normal, healthy absorbs about 2%–10%/Volumes/MHSF/MH-SANFRAN/MHSF027/MHS... 2880T_ch01_001-021.indd Page 2person 10/21/08 9:51:17 PM user-s131 of the iron in vegetables and about 10%–30% in meats. About 40% of the iron in meat, fish, and poultry is bound into molecules of heme, the iron-containing part of hemoglobin and myoglobin. Heme iron is much more readily absorbed (23%) than nonheme iron (2%–10%). (See the accompanying charts.) Cooking utensils can enhance the amount of iron delivered by the diet. The iron content of 100 g of spaghetti sauce simmered in a glass dish is 3 mg, but it is 87 mg when the sauce is cooked in an unenameled iron skillet. Even in the short time it takes to scramble eggs, their iron content can be tripled by cooking them in an iron pan.

Iron content of food derived from plants

Total dietary iron intake (daily average) 10% Heme iron

1.8 NAMES AND CHEMICAL SYMBOLS OF THE ELEMENTS 60% Nonheme iron

Nonheme iron

90% Nonheme iron

B

Looking forward/looking back margin notes show students the connections of concepts both in what they've learned previously and in what's to come.

F

Learning the chemical symbols of the more common elements is an important key to success in studying chemistry. Knowledge of chemical symbols is essential for writing chemical formulas (Section 1.10) and chemical equations (Section 6.6).

Each element has a unique name that, in most cases, was selected by it wide variety of rationales for choosing a name have been applied. Some geographical names; germanium is named after the native country of i coverer, and the elements francium and polonium are named after Fran The elements mercury, uranium, and neptunium are all named for p gets its name from the Greek word helios, for “sun,” because it was spectroscopically in the sun’s corona during an eclipse. Some elemen that reflect specific properties of the element or of the compounds Chlorine’s name is derived from the Greek chloros, denoting “greeni color of chlorine gas. Iridium gets its name from the Greek iris, mean this alludes to the varying colors of the compounds from which it was Abbreviations called chemical symbols also exist for the names of chemical symbol is a one- or two-letter designation for an element d element’s name. These chemical symbols are used more frequently tha names. Chemical symbols can be written more quickly than the names, a less space. A list of the known elements and their chemical symbols is giv The chemical symbols and names of the more frequently encountered elem in color in this table. Note that the first letter of a chemical symbol is always capitalized is not. Two-letter chemical symbols are often, but not always, the first tw element’s name. Eleven elements have chemical symbols that bear no relationship t English-language name. In ten of these cases, the symbol is derived name of the element; in the case of the element tungsten, a German name source. Most of these elements have been known for hundreds of years t th ti h L ti th l f i ti t El t h

1.3 PROPERTIES OF MATTER

Margin notes summarize key information, give tips for remembering or distinguishing between similar ideas, and provide additional details and links between concepts.

Chemical properties describe the ability of a substance to form new substances, either by reaction with other substances or by decomposition. Physical properties are properties associated with a substance’s physical existence. They can be determined without reference to any other substance, and determining them causes no change in the identity of the substance.

Various kinds of matter are distinguished from each other by their properties. A property is a distinguishing characteristic of a substance that is used in its identification and description. Each substance has a unique set of properties that distinguishes it from all other substances. Properties of matter are of two general types: physical and chemical. A physical property is a characteristic of a substance that can be observed without changing the basic identity of the substance. Common physical properties include color, odor, physical state (solid, liquid, or gas), melting point, boiling point, and hardness. During the process of determining a physical property, the physical appearance of a substance may change, but the substance’s identity does not. For example, it is impossible to measure the melting point of a solid without changing the solid into a liquid. Although the liquid’s appearance is much different from that of the solid, the substance is still the same; its chemical identity has not changed. Hence melting point is a physical property. A chemical property is a characteristic of a substance that describes the way the substance undergoes or resists change to form a new substance. For example, copper objects

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Within the chapters worked-out Examples follow the explanation of many concepts. These examples walk students through the thought process involved in problem solving, carefully outlining all the steps involved.

The value of the ideal gas constant (R) varies with the units chosen for pressure and volume. With pressure in atmospheres and volume in liters, R has the value R5

PV atm ? L 5 0.0821 nT mole ? K

The value of R is the same for all gases under normally encountered conditions of temperature, pressure, and volume. If three of the four variables in the ideal gas law equation are known, then the fourth can be calculated using the equation. Example 7.4 illustrates the use of the ideal gas law.

EXAMPLE 7.4 Using the Ideal Gas Law to Calculate the Volume of a Gas

The colorless, odorless, tasteless gas carbon monoxide, CO, is a by-product of incomplete combustion of any material that contains the element carbon. Calculate the volume, in liters, occupied by 1.52 moles of this gas at 0.992 atm pressure and a temperature of 65⬚C. Solution

This problem deals with only one set of conditions, so the ideal gas equation is applicable. Three of the four variables in the ideal gas equation (P, n, and T ) are given, and the fourth (V ) is to be calculated. P 5 0.992 atm    n 5 1.52 moles V 5 ? L  

T 5 658C 5 338 K

Rearranging the ideal gas equation to isolate V on the left side of the equation gives V5

nRT P

Because the pressure is given in atmospheres and the volume unit is liters, the R value 0.0821 is valid. Substituting known numerical values into the equation gives atm ? L b 1338 K2 mole ? K 0.992 atm

11.52 moles2 3 a0.0821 V5

Note that all the parts of the ideal gas constant unit cancel except for one, the volume part. Doing the arithmetic yields the volume of CO. V5a

1.52 3 0.0821 3 338 b L 5 42.5 L 0.992

Practice Exercise 7.4

Examples are immediately followed by a Practice Exercise to reinforce the information just presented.

Calculate the volume, in liters, occupied by 3.25 moles of Cl2 gas at 1.54 atm pressure and a temperature of 213⬚C. Answer: 84.2 L Cl2

7.8 DALTON’S LAW OF PARTIAL PRESSURES Figure 7.13 John Dalton (1766–1844) throughout his life had a particular interest in the study of weather. From “weather” he turned his attention to the nature of the atmosphere and then to the study of gases in general.

A sample of clean air is the most common example of a mixture of gases that do not react with one another.

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In a mixture of gases that do not react with one another, each type of molecule moves around in the container as though the other kinds were not there. This type of behavior is possible because a gas is mostly empty space, and attractions between molecules in the gaseous state are negligible at most temperatures and pressures. Each gas in the mixture occupies the entire volume of the container; that is, it distributes itself uniformly throughout the container. The molecules of each type strike the walls of the container as frequently and with the same energy as though they were the only gas in the mixture. Consequently, the pressure exerted by each gas in a mixture is the same as it would be if the gas were alone in the same container under the same conditions. The English scientist John Dalton (Figure 7.13) was the first to notice the independent behavior of gases in mixtures. In 1803, he published a summary statement concerning this behavior that is now known as Dalton’s law of partial pressures. Dalton’s law of partial

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O N C E P TS TO R E M E M B E R 1, 2, or 3 charge, respectively. Nonmetal atoms containing five, six, or seven valence electrons tend to gain electrons, producing ions of 3, 2, or 1 charge, respectively (Section 4.5). Chemical formulas for ionic compounds. The ratio in which positive and negative ions combine is the ratio that causes the total amount of positive and negative charges to add up to zero (Section 4.7). Structure of ionic compounds. Ionic solids consist of positive and negative ions arranged in such a way that each ion is surrounded by ions of the opposite charge (Section 4.8). Binary ionic compound nomenclature. Binary ionic compounds are named by giving the full name of the metallic element first, followed by a separate word containing the stem of the nonmetallic element name and the suffix -ide. A Roman numeral specifying ionic charge is appended to the name of the metallic element if it is a metal that exhibits variable ionic charge (Section 4.9). Polyatomic ions. A polyatomic ion is a group of covalently bonded atoms that has acquired a charge through the loss or gain of electrons. Polyatomic ions are very stable entities that generally maintain their identity during chemical reactions (Section 4.10).

Chemical bonds. Chemical bonds are the attractive forces that

Concepts to Remember and Key Reactions and Equations provide concise review of the material presented in the chapter, helping students prepare for exam.

hold atoms together in more complex units. Chemical bonds result from the transfer of valence electrons between atoms (ionic bond) or from the sharing of electrons between atoms (covalent bond) (Section 4.1). Valence electrons. Valence electrons, for representative elements, are the electrons in the outermost electron shell, which is the shell with the highest shell number. These electrons are particularly important in determining the bonding characteristics of a given atom (Section 4.2). Octet rule. In compound formation, atoms of representative elements lose, gain, or share electrons in such a way that their electron configurations become identical to those of the noble gas nearest them in the periodic table (Section 4.3). Ionic compounds. Ionic compounds commonly involve a metal atom and a nonmetal atom. Metal atoms lose one or more electrons, producing positive ions. Nonmetal atoms acquire the electrons lost by the metal atoms, producing negative ions. The oppositely charged ions attract one another, creating ionic bonds (Section 4.4). Charge magnitude for ions. Metal atoms containing one, two, or three valence electrons tend to lose such electrons, producing ions of

k

EY R E A C T I O N S A N D E Q U AT I O N S

1. Number of valence electrons for representative elements (Section 4.2) Number of valence electrons  periodic-table group number 2. Charges on metallic monatomic ions (Section 4.5) Group IA metals form 1 ions. Group IIA metals form 2 ions. Group IIIA metals form 3 ions.

3. Charges on nonmetallic monatomic ions (Section 4.5) Group VA nonmetals form 3 ions. Group VIA nonmetals form 2 ions. Group VIIA nonmetals form 1 ions.

EX E R CI SES a n d P RO O B LE EMS The members of each pair of problems in this section test similar material. Types of Chemical Bonds (Section 4.1) 4.1 4.2

Valence Electrons (Section 4.2) 4.3

4.4

4.5

4.6

4.7

Contrast the two general types of chemical bonds in terms of the mechanism by which they form. Contrast the two general types of chemical compounds in terms of their general physical properties. How many valence electrons do atoms with the following electron configurations have? b. 1s22s22p63s2 a. 1s22s2 c. 1s22s22p63s23p1 d. 1s22s22p63s23p64s23d104p2 How many valence electrons do atoms with the following electron configurations have? b. 1s22s22p63s23p1 a. 1s22s22p6 c. 1s22s22p63s1 d. 1s22s22p63s23p64s23d104p5

4.8

Extensive and varied Exercises and Problems at the end of each chapter are organized by topic and paired. These problems always involve only a single concept. Answers to selected problems can be found at the back of the book.

Write the complete electron configuration for each of the following representative elements. a. Period 2 element with four valence electrons b. Period 2 element with seven valence electrons c. Period 3 element with two valence electrons d. Period 3 element with five valence electrons Write the complete electron configuration for each of the following representative elements. a. Period 2 element with one valence electron b. Period 2 element with six valence electrons c. Period 3 element with seven valence electrons d. Period 3 element with three valence electrons

Lewis Symbols for Atoms (Section 4.2) Draw Lewis symbols for atoms of each of the following elements. a. 12Mg b. 19K c. 15P d. 36Kr 4.10 Draw Lewis symbols for atoms of each of the following elements. a. 13Al b. 20Ca c. 17Cl d. 4Be 4.9

Give the periodic-table group number and the number of valence electrons present for each of the following representative elements. b. 10Ne c. 20Ca d. 53I a. 3Li 4.11 Each of the following Lewis symbols represents a Period 2 Give the periodic-table group number and the number of valence element. Determine each element’s identity. electrons present for each of the following representative elements. b. 19K c. 15P d. 35Br a. 12Mg X b. XAM user-s131 c. X/Volumes/MHSF/MH-SANFRAN/MHSF027/MHS... d. X 2880T_ch04_083-107.indd Page 105a.10/19/08 11:05:09

4.53 What is a formula unit of an ionic compound? 4.54 In general terms, how many formula units are present in a crys-

tal of an ionic compound?

4.55 The following drawings represent solid-state ionic compounds,

New visual problem types are integrated throughout these problem sets and are designed to facilitate learning through the use of molecular models, pictorial representations of chemical systems, graphs, and other visual portrayals.

with red spheres denoting positive ions and blue spheres denoting negative ions.

I

II

III

IV

Which of these drawings could be used as a representation for each of the following ionic compounds? b. MgF2 c. K3N d. CaO a. Al2S3

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END-OF-CHAPTER REVIEW AND PRACTICE (continued)

A DD D ITIO NA L P R O BL L E MS 4.87 Fill in the blanks to complete the following table.

Positive Ion

Negative Ion

Chemical Formula

4.88 Fill in the blanks to complete the following table.

Name Magnesium hydroxide

BaBr2 Zn2

NO3 Iron(III) chlorate

Chemical Number of Number of Number of Symbol Protons Neutrons Electrons 28

31

77

120 9

PbO2 Co2 K

PO43 I

25 2 10

1

4.89 What would be the chemical symbol for an ion with each of the

Cu2SO4 Lithium nitride Al3

Net Charge

59 3 26 Fe

S2

following characteristics? a. A sodium ion with ten electrons b. A fluorine ion with ten electrons c. A sulfur ion with two fewer protons than electrons d. A calcium ion with two more protons than electrons

Additional Problems involve more than one concept and are more difficult than the Exercises and Problems.

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4.90 Write the formula of the ionic compound that could form from

4.91

4.92

4.93

4.94

the elements X and Z if a. X has two valence electrons and Z has seven valence electrons b. X has one valence electron and Z has six valence electrons c. X has three valence electrons and Z has five valence electrons d. X has six valence electrons and Z has two valence electrons Identify the Period 3 element that most commonly produces each of the following ions. b. X2 c. X3 d. X3 a. X2 Indicate whether each of the following compounds contains (1) only monatomic ions, (2) only polyatomic ions, (3) both monatomic and polyatomic ions, or (4) no ions. b. NaNO3 c. NH4CN d. AlP a. CaF2 Write chemical formulas (symbol and charge) for both kinds of ions present in each of the following compounds. d. Al2S3 a. KCl b. CaS c. BeF2 Give the chemical formula for, and the name of the compound formed from, each of the following pairs of ions.

4.95

4.96

4.97

4.98

b. K and NO3 a. Na and N3 c. Mg2 and O2 d. NH4 and PO43 Name each compound in the following pairs of binary ionic compounds. b. FeS and Fe2S3 a. SnCl4 and SnCl2 c. Cu3N and Cu3N2 d. NiI2 and NiI3 In which of the following pairs of binary ionic compounds do both members of the pair contain positive ions with the same charge? b. Cu2O and CuO a. Co2O3 and CoCl3 d. MgS and NaI c. K2O and Al2O3 Name each compound in the following pairs of polyatomicion-containing compounds. b. Pb3(PO4)2 and Pb3(PO4)4 a. CuNO3 and Cu(NO3)2 c. Mn(CN)3 and Mn(CN)2 d. Co(ClO3)2 and Co(ClO3)3 Write chemical formulas for the following compounds. a. Sodium sulfide b. Sodium sulfate c. Sodium sulfite d. Sodium thiosulfate

multiple-Choice Practice Test The Multiple-Choice Practice Test at the end each chapter provides a cumulative review.

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4.99 For which of the following elements is the listed number of

valence electrons correct? a. Mg (2 valence electrons) b. N (3 valence electrons) c. F (1 valence electron) d. S (2 valence electrons) 4.100 Which of the following is an incorrect statement about the number of electrons lost or gained by a representative element during ion formation? a. The number usually does not exceed three. b. The number is governed by the octet rule. c. The number is related to the position of the element in the periodic table. d. The number is the same as the number of valence electrons present. 4.101 Which of the following is a correct statement concerning the mechanism for ionic bond formation? a. Electrons are transferred from nonmetallic atoms to metallic atoms. b. Protons are transferred from the nuclei of metallic atoms to the nuclei of nonmetallic atoms. c. Sufficient electrons are transferred to form ions of equal but opposite charge. d. Electron loss is always equal to electron gain. 4.102 In which of the following pairings is the chemical formula not consistent with the ions shown? a. M2 and X3 (M3X2) b. M2 and X (MX2) c. M and X3 (MX3) d. M2 and X2 (MX)

4.103 The correct chemical formula for the ionic compound formed

between Mg and O is a. MgO b. Mg2O2

c. MgO2

d. Mg2O

4.104 In which of the following pairs of ionic compounds do both

4.105

4.106

4.107

4.108

members of the pair contain positive ions with a 1 charge? a. KCl and CaO b. Na3N and Li2S d. BaI2 and BeBr2 c. AlCl3 and MgF2 The correct chemical formula for the compound aluminum nitride is c. Al2N3 d. Al3N2 a. AlN b. AlN2 In which of the following pairs of metals are both members of the pair variable-charge metals? a. Na and Al b. Au and Ag c. Cu and Zn d. Fe and Ni In which of the following pairs of polyatomic ions do both members of the pair have the same charge? a. ammonium and phosphate b. sulfate and nitrate c. cyanide and hydroxide d. hydrogen carbonate and carbonate Which of the following ionic compounds contains 4 atoms per formula unit? a. Lithium nitride b. Potassium sulfide c. Copper(II) iodide d. Sodium cyanide

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General, Organic, and Biological Chemistry

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Basic Concepts About Matter Chapter Outline 1.1

Chemistry: The Study of Matter 1

1.2 Physical States of Matter 2

1

1.3 Properties of Matter 2 1.4 Changes in Matter 4

CHEMISTRY AT A GLANCE: Use of the Terms Physical and Chemical 5 1.5 Pure Substances and Mixtures 6 1.6 Elements and Compounds 7

CHEMISTRY AT A GLANCE: Classes of Matter 8 1.7 Discovery and Abundance of the Elements 9 1.8 Names and Chemical Symbols of the Elements 11 1.9 Atoms and Molecules 12 1.10 Chemical Formulas 15

CHEMICAL CONNECTIONS “Good” Versus “Bad” Properties for a Chemical Substance 3

Numerous physical and chemical changes in matter occur during a volcanic eruption.

Elemental Composition of the Human Body 11

n this chapter we address the question, “What exactly is chemistry about?” In addition, we consider common terminology associated with the field of chemistry. Much of this terminology is introduced in the context of the ways in which matter is classified. Like all other sciences, chemistry has its own specific language. It is necessary to restrict the meanings of some words so that all chemists (and those who study chemistry) can understand a given description of a chemical phenomenon in the same way.

I

1 1 CHEMISTRY: THE STUDY OF MATTER

The universe is composed entirely of matter and energy.

Chemistry is the field of study concerned with the characteristics, composition, and transformations of matter. What is matter? Matter is anything that has mass and occupies space. The term mass refers to the amount of matter present in a sample. Matter includes all things—both living and nonliving—that can be seen (such as plants, soil, and rocks), as well as things that cannot be seen (such as air and bacteria). Various forms of energy such as heat, light, and electricity are not considered to be matter. However, chemists must be concerned with energy as well as with matter because nearly all changes that matter undergoes involve the release or absorption of energy. The scope of chemistry is extremely broad, and it touches every aspect of our lives. An iron gate rusting, a chocolate cake baking, the diagnosis and treatment of a heart attack, the propulsion of a jet airliner, and the digesting of food all fall within the realm of chemistry. The key to understanding such diverse processes is an understanding of the fundamental nature of matter, which is what we now consider.

1

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Chapter 1 Basic Concepts About Matter

Figure 1.1 (a) A solid has a definite shape and a definite volume. (b) A liquid has an indefinite shape—it takes the shape of its container—and a definite volume. (c) A gas has an indefinite shape and an indefinite volume—it assumes the shape and volume of its container.

(a)

(b)

(c)

1.2 PHYSICAL STATES OF MATTER

The volume of a sample of matter is a measure of the amount of space occupied by the sample.

Figure 1.2 Water can be found in the solid, liquid, and vapor (gaseous) forms simultaneously, as shown here at Yellowstone National Park.

Chemical properties describe the ability of a substance to form new substances, either by reaction with other substances or by decomposition. Physical properties are properties associated with a substance’s physical existence. They can be determined without reference to any other substance, and determining them causes no change in the identity of the substance.

Three physical states exist for matter: solid, liquid, and gas. The classification of a given matter sample in terms of physical state is based on whether its shape and volume are definite or indefinite. Solid is the physical state characterized by a definite shape and a definite volume. A dollar coin has the same shape and volume whether it is placed in a large container or on a table top (Figure 1.1a). For solids in powdered or granulated forms, such as sugar or salt, a quantity of the solid takes the shape of the portion of the container it occupies, but each individual particle has a definite shape and definite volume. Liquid is the physical state characterized by an indefinite shape and a definite volume. A liquid always takes the shape of its container to the extent that it fills the container (Figure 1.1b). Gas is the physical state characterized by an indefinite shape and an indefinite volume. A gas always completely fills its container, adopting both the container’s volume and its shape (Figure 1.1c). The state of matter observed for a particular substance depends on its temperature, the surrounding pressure, and the strength of the forces holding its structural particles together. At the temperatures and pressures normally encountered on Earth, water is one of the few substances found in all three of its physical states: solid ice, liquid water, and gaseous steam (Figure 1.2). Under laboratory conditions, states other than those commonly observed can be attained for almost all substances. Oxygen, which is nearly always thought of as a gas, becomes a liquid at ⫺183°C and a solid at ⫺218°C. The metal iron is a gas at extremely high temperatures (above 3000°C).

1.3 PROPERTIES OF MATTER Various kinds of matter are distinguished from each other by their properties. A property is a distinguishing characteristic of a substance that is used in its identification and description. Each substance has a unique set of properties that distinguishes it from all other substances. Properties of matter are of two general types: physical and chemical. A physical property is a characteristic of a substance that can be observed without changing the basic identity of the substance. Common physical properties include color, odor, physical state (solid, liquid, or gas), melting point, boiling point, and hardness. During the process of determining a physical property, the physical appearance of a substance may change, but the substance’s identity does not. For example, it is impossible to measure the melting point of a solid without changing the solid into a liquid. Although the liquid’s appearance is much different from that of the solid, the substance is still the same; its chemical identity has not changed. Hence melting point is a physical property. A chemical property is a characteristic of a substance that describes the way the substance undergoes or resists change to form a new substance. For example, copper objects

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1.3 Properties of Matter

c

HEMICAL

onnections

3

“Good” Versus “Bad” Properties for a Chemical Substance

It is important not to judge the significance or usefulness of a chemical substance on the basis of just one or two of the many chemical and physical properties it exhibits. Possession of a “bad” property, such as toxicity or a strong noxious odor, does not mean that a chemical substance has nothing to contribute to the betterment of human society. A case in point is the substance carbon monoxide. Everyone knows that it is a gaseous air pollutant present in automobile exhaust and cigarette smoke and that it is toxic to human beings. For this reason, some people automatically label carbon monoxide a “bad” substance, a substance we do not need or want. Indeed, carbon monoxide is toxic to human beings. It impairs human health by reducing the oxygen-carrying capacity of the blood. Carbon monoxide does this by interacting with the hemoglobin in red blood cells in a way that prevents the hemoglobin from distributing oxygen throughout the body. Someone who dies from carbon monoxide poisoning actually dies from lack of oxygen. The fact that carbon monoxide is colorless, odorless, and tasteless is very significant. Because of these properties, carbon monoxide gives no warning of its initial presence. There are several other common air pollutants that are more toxic than carbon monoxide. However, they have properties that give warning of their presence and hence they are not considered as “dangerous” as carbon monoxide.

Despite its toxicity, carbon monoxide plays an important role in the maintenance of the high standard of living we now enjoy. Its contribution lies in the field of iron metallurgy and the production of steel. The isolation of iron from iron ores, necessary for the production of steel, involves a series of high-temperature reactions, carried out in a blast furnace, in which the iron content of molten iron ores reacts with carbon monoxide. These reactions release the iron from its ores. The carbon monoxide needed in steel making is obtained by reacting coke (a product derived by heating coal to a high temperature without air being present) with oxygen. The industrial consumption of the metal iron, both in the United States and worldwide, is approximately ten times greater than that of all other metals combined. Steel production accounts for nearly all of this demand for iron. Without steel, our standard of living would drop dramatically, and carbon monoxide is necessary for the production of steel. Is carbon monoxide a “good” or a “bad” chemical substance? The answer to this question depends on the context in which the carbon monoxide is encountered. In terms of air pollution, it is a “bad” substance. In terms of steel making, it is a “good” substance. A similar “good–bad” dichotomy exists for almost every chemical substance.

turn green when exposed to moist air for long periods of time (Figure 1.3); this is a chemical property of copper. The green coating formed on the copper is a new substance that results from the copper’s reaction with oxygen, carbon dioxide, and water present in air. The properties of this new substance (the green coating) are very different from those of metallic copper. On the other hand, gold objects resist change when exposed to air for long periods of time. The lack of reactivity of gold with air is a chemical property of gold. Most often the changes associated with chemical properties result from the interaction (reaction) of a substance with one or more other substances. However, the presence of a second substance is not an absolute requirement. Sometimes the presence of energy (usually heat or light) can trigger the change called decomposition. That hydrogen peroxide, in the presence of either heat or light, decomposes into the substances water and oxygen is a chemical property of hydrogen peroxide. When we specify chemical properties, we usually give conditions such as temperature and pressure because they influence the interactions between substances. For example, the gases oxygen and hydrogen are unreactive toward each other at room temperature, but they interact explosively at a temperature of several hundred degrees.

EXAMPLE 1.1 CCllassssiiffyyinng Prop Prop Pr oper erti ties ties es as Phhyyssic ical cal al or Chheem miccal a

Classify each of the following properties for selected metals as a physical property or a chemical property. a. b. c. d.

Iron metal rusts in an atmosphere of moist air. Mercury metal is a liquid at room temperature. Nickel metal dissolves in acid to produce a light green solution. Potassium metal has a melting point of 63°C. (continued)

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Chapter 1 Basic Concepts About Matter

Solution

a. Chemical property. The interaction of iron metal with moist air produces a new substance (rust). b. Physical property. Visually determining the physical state of a substance does not produce a new substance. c. Chemical property. A change in color indicates the formation of a new substance. d. Physical property. Measuring the melting point of a substance does not change the substance’s composition.

Practice Exercise 1.1 Classify each of the following properties for selected metals as a physical property or a chemical property. a. b. c. d. Figure 1.3 The green color of the Statue of Liberty results from the reaction of the copper skin of the statue with the components of air. That copper will react with the components of air is a chemical property of copper.

Titanium metal can be drawn into thin wires. Silver metal shows no sign of reaction when placed in hydrochloric acid. Copper metal possesses a reddish brown color. Beryllium metal, when inhaled in a finely divided form, can produce serious lung disease.

Answers: a. physical property; b. chemical property; c. physical property; d. chemical property

1.4 CHANGES IN MATTER Changes in matter are common and familiar occurrences. Changes take place when food is digested, paper is burned, and a pencil is sharpened. Like properties of matter, changes in matter are classified into two categories: physical and chemical. A physical change is a process in which a substance changes its physical appearance but not its chemical composition. A new substance is never formed as a result of a physical change. A change in physical state is the most common type of physical change. Melting, freezing, evaporation, and condensation are all changes of state. In any of these processes, the composition of the substance undergoing change remains the same even though its physical state and appearance change. The melting of ice does not produce a new substance; the substance is water both before and after the change. Similarly, the steam produced from boiling water is still water. A chemical change is a process in which a substance undergoes a change in chemical composition. Chemical changes always involve conversion of the material or materials under consideration into one or more new substances, each of which has properties and composition distinctly different from those of the original materials. Consider, for example, the rusting of iron objects left exposed to moist air (Figure 1.4). The reddish brown substance (the rust) that forms is a new substance with chemical properties that are obviously different from those of the original iron.

Figure 1.4 As a result of chemical change, bright steel girders become rusty when exposed to moist air.

EXAMPLE 1.2 Corr Co rrec rec e t Us Use ooff the he Ter erms rmss Phys Ph ysiiccaall and ys nd Chhemic em mic ical caall in Deesc scri ribi bing ng Chhaang nges es

Complete each of the following statements about changes in matter by placing the word physical or chemical in the blank. a. The fashioning of a piece of wood into a round table leg involves a change. b. The vigorous reaction of potassium metal with water to produce hydrogen gas is a change. change. c. Straightening a bent piece of iron with a hammer is an example of a change. d. The ignition and burning of a match involve a

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1.4 Changes in Matter

5

Solution

a. b. c. d.

Physical changes need not involve a change of state. Pulverizing an aspirin tablet into a powder and cutting a piece of adhesive tape into small pieces are physical changes that involve only the solid state.

Physical. The table leg is still wood. No new substances have been formed. Chemical. A new substance, hydrogen, is produced. Physical. The piece of iron is still a piece of iron. Chemical. New gaseous substances, as well as heat and light, are produced as the match burns.

Practice Exercise 1.2 Complete each of the following statements about changes in matter by placing the word physical or chemical in the blank. a. The destruction of a newspaper through burning involves a change. change. b. The grating of a piece of cheese is a c. The heating of a blue powdered material to produce a white glassy substance and a gas change. is a change. d. The crushing of ice cubes to make ice chips is a Answers: a. chemical; b. physical; c. chemical; d. physical

Chemists study the nature of changes in matter to learn how to bring about favorable changes and prevent undesirable ones. The control of chemical change has been a major factor in attainment of the modern standard of living now enjoyed by most people in the developed world. The many plastics, synthetic fibers, and prescription drugs now in common use are derived via controlled chemical change. The Chemistry at a Glance feature below reviews the ways in which the terms physical and chemical are used to describe the properties of substances and the changes

Use of the Terms Physical and Chemical PHYSICAL

CHEMICAL

This term conveys the idea that the composition (chemical identity) of a substance DOES NOT CHANGE.

This term conveys the idea that the composition (chemical identity) of a substance DOES CHANGE.

Physical Properties Properties observable without changing composition Color and shape Solid, liquid, or gas Boiling point, melting point

Physical Changes

Chemical Properties

Chemical Changes

Changes observable without changing composition Change in physical state (melting, boiling, freezing, etc.) Change in state of subdivision with no change in physical state (pulverizing a solid)

Properties that describe how a substance changes (or resists change) to form a new substance Flammability (or nonflammability) Decomposition at a high temperature (or lack of decomposition) Reaction with chlorine (or lack of reaction with chlorine)

Changes in which one or more new substances are formed Decomposition Reaction with another substance

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that substances undergo. Note that the term physical, used as a modifier, always conveys the idea that the composition (chemical identity) of a substance did not change, and that the term chemical, used as a modifier, always conveys the idea that the composition of a substance did change.

1.5 PURE SUBSTANCES AND MIXTURES Substance is a general term used to denote any variety of matter. Pure substance is a specific term that is applied to matter that contains only a single substance.

All samples of a pure substance, no matter what their source, have the same properties under the same conditions.

Most naturally occurring samples of matter are mixtures. Gold and diamond are two of the few naturally occurring pure substances. Despite their scarcity in nature, numerous pure substances are known. They are obtained from natural mixtures by using various types of separation techniques or are synthesized in the laboratory from naturally occurring materials.

In addition to its classification by physical state (Section 1.2), matter can also be classified in terms of its chemical composition as a pure substance or as a mixture. A pure substance is a single kind of matter that cannot be separated into other kinds of matter by any physical means. All samples of a pure substance contain only that substance and nothing else. Pure water is water and nothing else. Pure sucrose (table sugar) contains only that substance and nothing else. A pure substance always has a definite and constant composition. This invariant composition dictates that the properties of a pure substance are always the same under a given set of conditions. Collectively, these definite and constant physical and chemical properties constitute the means by which we identify the pure substance. A mixture is a physical combination of two or more pure substances in which each substance retains its own chemical identity. Components of a mixture retain their identity because they are physically mixed rather than chemically combined. Consider a mixture of small rock salt crystals and ordinary sand. Mixing these two substances changes neither the salt nor the sand in any way. The larger, colorless salt particles are easily distinguished from the smaller, light-gray sand granules. One characteristic of any mixture is that its components can be separated by using physical means. In our salt–sand mixture, the larger salt crystals could be—though very tediously—“picked out” from the sand. A somewhat easier separation method would be to dissolve the salt in water, which would leave the undissolved sand behind. The salt could then be recovered by evaporation of the water. Figure 1.5a shows a heterogeneous mixture of potassium dichromate (orange crystals) and iron filings. A magnet can be used to separate the components of this mixture (Figure 1.5b). Another characteristic of a mixture is variable composition. Numerous different salt– sand mixtures, with compositions ranging from a slightly salty sand mixture to a slightly sandy salt mixture, could be made by varying the amounts of the two components. Mixtures are subclassified as heterogeneous or homogeneous. This subclassification is based on visual recognition of the mixture’s components. A heterogeneous mixture is a mixture that contains visibly different phases (parts), each of which has different properties. A nonuniform appearance is a characteristic of all heterogeneous mixtures. Examples include chocolate chip cookies and blueberry muffins. Naturally occurring heterogeneous mixtures include rocks, soils, and wood. A homogeneous mixture is a mixture that contains only one visibly distinct phase (part), which has uniform properties throughout. The components present in a homogeneous mixture cannot be visually distinguished. A sugar–water mixture in which all of the

Figure 1.5 (a) A magnet (on the left) and a mixture consisting of potassium dichromate (the orange crystals) and iron filings. (b) The magnet can be used to separate the iron filings from the potassium dichromate.

(a)

(b)

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1.6 Elements and Compounds

Figure 1.6 Matter falls into two basic

7

MATTER

classes: pure substances and mixtures. Mixtures, in turn, may be homogeneous or heterogeneous.

Anything that has mass and occupies space

PURE SUBSTANCE

MIXTURE

Only one substance present

Physical combination of two or more substances

HOMOGENEOUS MIXTURE One visible phase

HETEROGENEOUS MIXTURE Two or more visible phases

sugar has dissolved has an appearance similar to that of pure water. Air is a homogeneous mixture of gases; motor oil and gasoline are multicomponent homogeneous mixtures of liquids; and metal alloys such as 14-karat gold (a mixture of copper and gold) are examples of homogeneous mixtures of solids. The homogeneity present in solid-state metallic alloys is achieved by mixing the metals while they are in the molten state. Figure 1.6 summarizes what we have learned thus far about various classifications of matter.

1.6 ELEMENTS AND COMPOUNDS Both elements and compounds are pure substances.

B

F

The definition for the term element that is given here will do for now. After considering the concept of atomic number (Section 3.2), we will give a more precise definition.

Chemists have isolated and characterized an estimated 9 million pure substances. A very small number of these pure substances, 117 to be exact, are different from all of the others. They are elements. All of the rest, the remaining millions, are compounds. What distinguishes an element from a compound? An element is a pure substance that cannot be broken down into simpler pure substances by chemical means such as a chemical reaction, an electric current, heat, or a beam of light. The metals gold, silver, and copper are all elements. A compound is a pure substance that can be broken down into two or more simpler pure substances by chemical means. Water is a compound. By means of an electric current, water can be broken down into the gases hydrogen and oxygen, both of which are elements. The ultimate breakdown products for any compound are elements. A compound’s properties are always different from those of its component elements, because the elements are chemically rather than physically combined in the compound (Figure 1.7).

Figure 1.7 A pure substance can be

PURE SUBSTANCE

either an element or a compound.

Only one substance present

ELEMENT Cannot be broken down into simpler substances by chemical or physical means

COMPOUND Can be broken down into constituent elements by chemical, but not physical, means

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Classes of Matter Classes of Matter Pure Substances

Mixtures

Only one substance present Definite and constant composition Properties always the same under the same conditions

Physical combination of two or more substances Composition can vary Properties can vary with composition

Elements Cannot be broken down into simpler substances by chemical or physical means Building blocks for all other types of matter 117 elements known

Every known compound is made up of some combination of two or more of the 117 known elements. In any given compound, the elements are combined chemically in fixed proportions by mass.

EXAMPLE 1.3 Thhe ”C ”Com Com omppoosi sittiion on” n” Diiff D fferen erren ence ce Beettwe ce tw weeen en a Mixt Mi xtur ure an and nd a Co Compou mpoouund mp undd

Compounds Can be broken down into constituent elements by chemical, but not physical, means Chemical combination of two or more elements Have definite, constant, elemental composition

Homogeneous Mixtures One visible phase Same properties throughout

Heterogeneous Mixtures Two or more visible phases Different properties in different phases

Even though two or more elements are obtained from decomposition of compounds, compounds are not mixtures. Why is this so? Remember, substances can be combined either physically or chemically. Physical combination of substances produces a mixture. Chemical combination of substances produces a compound, a substance in which combining entities are bound together. No such binding occurs during physical combination. Example 1.3, which involves two comparisons involving locks and their keys, nicely illustrates the difference between compounds and mixtures. The Chemistry at a Glance feature above summarizes what we have learned thus far about the subdivisions of matter called pure substances, elements, compounds, and mixtures.

Consider two boxes with the following contents: the first contains 10 locks and 10 keys that fit the locks; the second contains 10 locks with each lock’s key inserted into the cylinder. Which box has contents that would be an analogy for a mixture and which box has contents that would be an analogy for a compound? Solution

The box containing the locks with their keys inserted in the cylinder represents the compound. Two objects withdrawn from this box will always be the same; each will be a lock with its associated key. Each item in the box has the same “composition.” The box containing separated locks and keys represents the mixture. Two objects withdrawn from this box need not be the same; results could be two locks, two keys, or a lock and a key. All items in the box do not have the same “composition.”

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1.7 Discovery and Abundance of the Elements

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Practice Exercise 1.3 Consider two boxes with the following contents: the first contains 30 bolts and 30 nuts that fit the bolts; the second contains the same number of bolts and nuts with the difference that each bolt has a nut screwed on it. Which box has contents that would be an analogy for a mixture and which box has contents that would be an analogy for a compound? Answers: first box, mixture; second box, compound

There are three major property distinctions between compounds and mixtures. 1. Compounds have properties distinctly different from those of the substances that combined to form the compound. The components of mixtures retain their individual properties. 2. Compounds have a definite composition. Mixtures have a variable composition. 3. Physical methods are sufficient to separate the components of a mixture. The components of a compound cannot be separated by physical methods; chemical methods are required.

A student who attended a university in the year 1700 would have been taught that 13 elements existed. In 1750 he or she would have learned about 16 elements, in 1800 about 34, in 1850 about 59, in 1900 about 82, and in 1950 about 98. Today’s total of 117 elements was reached in 2006.

Figure 1.8 summarizes the thought processes a chemist goes through in classifying a sample of matter as a heterogeneous mixture, a homogeneous mixture, an element, or a compound. This figure is based on the following three questions about a sample of matter: 1. Does the sample of matter have the same properties throughout? 2. Are two or more different substances present? 3. Can the pure substance be broken down into simpler substances?

1.7 DISCOVERY AND ABUNDANCE OF THE ELEMENTS The discovery and isolation of the 117 known elements, the building blocks for all matter, have taken place over a period of several centuries. Most of the discoveries have occurred since 1700, the 1800s being the most active period. Eighty-eight of the 117 elements occur naturally, and 29 have been synthesized in the laboratory by bombarding samples of naturally occurring elements with small particles. Figure 1.9 shows samples of selected naturally occurring elements. The synthetic (laboratory-produced) elements are all unstable (radioactive) and usually revert quickly back to naturally occurring elements (see Section 11.5). The naturally occurring elements are not evenly distributed on Earth and in the universe. What is startling is the nonuniformity of the distribution. A small number of elements account for the majority of elemental particles (atoms). (An atom is the smallest particle of an element that can exist; see Section 1.9.)

Figure 1.8 Questions used in classifying matter into various categories.

Does the sample of matter have the same properties throughout?

No

Yes

Homogeneous

Heterogeneous

Yes

Are two or more different substances present?

Heterogeneous mixture

No

Element

Are two or more different substances present?

No

No

Pure substance (in two or more physical states)

Pure substance (in one physical state)

Can the pure substance be broken down into simpler substances?

Yes

Homogeneous mixture

Yes

Compound

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Chapter 1 Basic Concepts About Matter

Figure 1.9 Outward physical appearance of selected naturally occurring elements. Center: Sulfur. From upper right, clockwise: Arsenic, iodine, magnesium, bismuth, and mercury.

Any increase in the number of known elements from 117 will result from the production of additional synthetic elements. Current chemical theory strongly suggests that all naturally occurring elements have been identified. The isolation of the last of the known naturally occurring elements, rhenium, occurred in 1925.

Studies of the radiation emitted by stars enable scientists to estimate the elemental composition of the universe (Figure 1.10a). Results indicate that two elements, hydrogen and helium, are absolutely dominant. All other elements are mere “impurities” when their abundances are compared with those of these two dominant elements. In this big picture, in which Earth is but a tiny microdot, 91% of all elemental particles (atoms) are hydrogen, and nearly all of the remaining 9% are helium. If we narrow our view to the chemical world of humans—Earth’s crust (its waters, atmosphere, and outer solid surface)—a different perspective emerges. Again, two elements dominate, but this time they are oxygen and silicon. Figure 1.10b provides information on elemental abundances for Earth’s crust. The numbers given are atom percents—that is, the percentage of total atoms that are of a given type. Note that the eight elements listed (the only elements with atom percents greater than 1%) account for over 98% of total atoms in Earth’s crust. Note also the dominance of oxygen and silicon; these two elements account for 80% of the atoms that make up the chemical world of humans. Oxygen, the most abundant element in Earth’s crust, was isolated in pure form for the first time in 1774 by the English chemist and theologian Joseph Priestly (1733–1804). Discovery years for the other “top five” elements of Earth’s crust are 1824 (silicon), 1827 (aluminum), 1766 (hydrogen), and 1808 (calcium).

Figure 1.10 Abundance of elements (in atom percent) in the universe (a) and in Earth’s crust (b).

Helium 9% All others < 0.1%

Calcium 2.6% Magnesium 2.4% Hydrogen 2.9% Iron 2.2% Sodium 2.1% All others 1.5% Aluminum 6.1%

Silicon 20.1%

Hydrogen 91%

(a) Universe

Oxygen 60.1%

(b) Earth’s crust

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1.8 Names and Chemical Symbols of the Elements

c

HEMICAL

onnections

11

Elemental Composition of the Human Body

The distribution of elements in the human body and other living systems is very different from that found in Earth’s crust. This distribution is the result of living systems selectively taking up matter from their external environment rather than simply accumulating matter representative of their surroundings. Food intake constitutes the primary selective intake process. Nitrogen 2.4% Carbon 10.7% All others 0.7%

Only four elements are found in the human body at atom percent levels greater than 1%. Hydrogen, carbon, and nitrogen are all much more abundant than in Earth’s crust (Figure 1.10b), and oxygen is significantly less abundant than in Earth’s crust. The dominance of hydrogen and oxygen in the human body reflects its high water content. Hydrogen is over twice as abundant as oxygen, largely because water contains hydrogen and oxygen in a 2-to-1 atom ratio. Carbohydrates, fats, and proteins, nutrients required by the human body in large amounts, are all sources of carbon, hydrogen, and oxygen. Proteins are the body’s primary nitrogen source. Hydrogen

Oxygen 25.7%

Hydrogen 60.5%

Oxygen

Carbon

Nitrogen

Water Carbohydrate Fat Protein

1.8 NAMES AND CHEMICAL SYMBOLS OF THE ELEMENTS

B

F

Learning the chemical symbols of the more common elements is an important key to success in studying chemistry. Knowledge of chemical symbols is essential for writing chemical formulas (Section 1.10) and chemical equations (Section 6.6).

Each element has a unique name that, in most cases, was selected by its discoverer. A wide variety of rationales for choosing a name have been applied. Some elements bear geographical names; germanium is named after the native country of its German discoverer, and the elements francium and polonium are named after France and Poland. The elements mercury, uranium, and neptunium are all named for planets. Helium gets its name from the Greek word helios, for “sun,” because it was first observed spectroscopically in the sun’s corona during an eclipse. Some elements carry names that reflect specific properties of the element or of the compounds that contain it. Chlorine’s name is derived from the Greek chloros, denoting “greenish-yellow,” the color of chlorine gas. Iridium gets its name from the Greek iris, meaning “rainbow”; this alludes to the varying colors of the compounds from which it was isolated. Abbreviations called chemical symbols also exist for the names of the elements. A chemical symbol is a one- or two-letter designation for an element derived from the element’s name. These chemical symbols are used more frequently than the elements’ names. Chemical symbols can be written more quickly than the names, and they occupy less space. A list of the known elements and their chemical symbols is given in Table 1.1. The chemical symbols and names of the more frequently encountered elements are shown in color in this table. Note that the first letter of a chemical symbol is always capitalized and the second is not. Two-letter chemical symbols are often, but not always, the first two letters of the element’s name. Eleven elements have chemical symbols that bear no relationship to the element’s English-language name. In ten of these cases, the symbol is derived from the Latin name of the element; in the case of the element tungsten, a German name is the symbol’s source. Most of these elements have been known for hundreds of years and date back to the time when Latin was the language of scientists. Elements whose chemical symbols are derived from non-English names are marked with an asterisk in Table 1.1.

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TABLE 1.1 The Chemical Symbols for the Elements The names and symbols of the more frequently encountered elements are shown in color.

Ac Ag Al Am Ar As At Au B Ba Be Bh Bi Bk Br C Ca Cd Ce Cf Cl Cm Co Cr Cs Cu Db Ds Dy Er Es Eu F Fe Fm Fr Ga

actinium silver* aluminum americium argon arsenic astatine gold* boron barium beryllium bohrium bismuth berkelium bromine carbon calcium cadmium cerium californium chlorine curium cobalt chromium cesium copper* dubnium darmstadtium dysprosium erbium einsteinium europium fluorine iron* fermium francium gallium

Gd Ge H He Hf Hg Ho Hs I In Ir K Kr La Li Lr Lu Md Mg Mn Mo Mt N Na Nb Nd Ne Ni No Np O Os P Pa Pb Pd Pm

gadolinium germanium hydrogen helium hafnium mercury* holmium hassium iodine indium iridium potassium* krypton lanthanum lithium lawrencium lutetium mendelevium magnesium manganese molybdenum meitnerium nitrogen sodium* niobium neodymium neon nickel nobelium neptunium oxygen osmium phosphorus protactinium lead* palladium promethium

Po Pr Pt Pu Ra Rb Re Rf Rg Rh Rn Ru S Sb Sc Se Sg Si Sm Sn Sr Ta Tb Tc Te Th Ti Tl Tm U V W Xe Y Yb Zn Zr

polonium praseodymium platinum plutonium radium rubidium rhenium rutherfordium roentgenium rhodium radon ruthenium sulfur antimony* scandium selenium seaborgium silicon samarium tin* strontium tantalum terbium technetium tellurium thorium titanium thallium thulium uranium vanadium tungsten* xenon yttrium ytterbium zinc zirconium

Only 111 elements are listed in this table. The remaining six elements, discovered (synthesized) between 1996 and 2006, are yet to be named. * These elements have symbols that were derived from non-English names.

1.9 ATOMS AND MOLECULES

Figure 1.11 A computer reconstruction of the surface of a crystal as observed with a scanning tunneling microscope. The image reveals a regular pattern of individual atoms. The color was added to the image by the computer and is used to show that two different kinds of atoms are present.

Consider the process of subdividing a sample of the element gold (or any other element) into smaller and smaller pieces. It seems reasonable that eventually a “smallest possible piece” of gold would be reached that could not be divided further and still be the element gold. This smallest possible unit of gold is called a gold atom. An atom is the smallest particle of an element that can exist and still have the properties of the element. A sample of any element is composed of atoms of a single type, those of that element. In contrast, a compound must have two or more types of atoms present, because by definition at least two elements must be present (Section 1.6). No one ever has seen or ever will see an atom with the naked eye; they are simply too small for such observation. However, sophisticated electron microscopes, with magnification factors in the millions, have made it possible to photograph “images” of individual atoms (Figure 1.11).

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1.9 Atoms and Molecules

254,000,000 atoms ... 1 inch

1

Figure 1.12 254 million atoms arranged in a straight line would extend a distance of approximately 1 inch.

B

F

Reasons for the tendency of atoms to assemble into molecules and information on the binding forces involved are considered in Chapter 4.

The Latin word mole means “a mass.” The word molecule denotes “a little mass.”

B

F

The concept that heteroatomic molecules are the building blocks for all compounds will have to be modified when certain solids, called ionic solids, are considered in Section 4.8.

13

Atoms are incredibly small particles. Atomic dimensions, although not directly measurable, can be calculated from measurements made on large-size samples of elements. The diameter of an atom is approximately four-billionths of an inch. If atoms of such diameter were arranged in a straight line, it would take 254 million of them to extend a distance of 1 inch (see Figure 1.12). Free atoms are rarely encountered in nature. Instead, under normal conditions of temperature and pressure, atoms are almost always found together in aggregates or clusters ranging in size from two atoms to numbers too large to count. When the group or cluster of atoms is relatively small and bound together tightly, the resulting entity is called a molecule. A molecule is a group of two or more atoms that functions as a unit because the atoms are tightly bound together. This resultant “package” of atoms behaves in many ways as a single, distinct particle would. A diatomic molecule is a molecule that contains two atoms. It is the simplest type of molecule that can exist. Next in complexity are triatomic molecules. A triatomic molecule is a molecule that contains three atoms. Continuing on numerically, we have tetraatomic molecules, pentatomic molecules, and so on. The atoms present in a molecule may all be of the same kind, or two or more kinds may be present. On the basis of this observation, molecules are classified into two categories: homoatomic and heteroatomic. A homoatomic molecule is a molecule in which all atoms present are of the same kind. A substance containing homoatomic molecules must be an element. The fact that homoatomic molecules exist indicates that individual atoms are not always the preferred structural unit for an element. The gaseous elements hydrogen, oxygen, nitrogen, and chlorine exist in the form of diatomic molecules. There are four atoms present in a gaseous phosphorus molecule and eight atoms present in a gaseous sulfur molecule (see Figure 1.13). A heteroatomic molecule is a molecule in which two or more kinds of atoms are present. Substances that contain heteroatomic molecules must be compounds because the presence of two or more kinds of atoms reflects the presence of two or more kinds of elements. The number of atoms present in the heteroatomic molecules associated with compounds varies over a wide range. A water molecule contains 3 atoms: 2 hydrogen atoms and 1 oxygen atom. The compound sucrose (table sugar) has a much larger molecule: 45 atoms are present, of which 12 are carbon atoms, 22 are hydrogen atoms, and 11 are oxygen atoms. Figure 1.14 shows general models for four simple types of heteroatomic molecules. Comparison of parts (c) and (d) of this figure shows that molecules with the same number of atoms need not have the same arrangement of atoms. A molecule is the smallest particle of a compound capable of a stable independent existence. Continued subdivision of a quantity of table sugar to yield smaller and smaller amounts would ultimately lead to the isolation of one single “unit” of table sugar: a molecule of table sugar. This table sugar molecule could not be broken down any further and still exhibit the physical and chemical properties of table sugar. The table sugar molecule could be broken down further by chemical (not physical) means to produce atoms, but if that occurred, we would no longer have table sugar. The molecule is the limit of physical subdivision. The atom is the limit of chemical subdivision.

Figure 1.13 Molecular structure of (a) chlorine molecule, (b) phosphorus molecule, and (c) sulfur molecule.

P Cl

Cl

(a) Chlorine molecule

P

S P

S S

S

S

S

P

S

(b) Phosphorus molecule

(c) Sulfur molecule

S

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Figure 1.14 Depictions of various simple heteroatomic molecules using models. Spheres of different sizes and colors represent different kinds of atoms.

A

B

B

A

(a) A diatomic molecule containing one atom of A and one atom of B

A

(b) A triatomic molecule containing two atoms of A and one atom of B

A A

A B

A

B

(c) A tetraatomic molecule containing two atoms of A and two atoms of B

EXAMPLE 1.4 Clas Cl las assi sify si fyin ing M Mooleecu cuule lees oonn thhee Bassiss of Nu Numb mbers mber ers er ooff and nd Typ ypes es of AAttom oms

A B

(d) A tetraatomic molecule containing three atoms of A and one atom of B

Classify each of the following molecules as (1) diatomic, triatomic, etc., (2) homoatomic or heteroatomic, and (3) representing an element or a compound.

(a)

(b)

(c)

(d)

Solution

a. Tetraatomic (four atoms); heteroatomic (two kinds of atoms); a compound (two kinds of atoms) b. Triatomic (three atoms); homoatomic (only one kind of atom); an element (one kind of atom) c. Tetraatomic (four atoms); heteroatomic (two kinds of atoms); a compound (two kinds of atoms) d. Hexatomic (six atoms); heteroatomic (three kinds of atoms); a compound (three kinds of atoms)

Practice Exercise 1.4 Classify each of the following molecules as (1) diatomic, triatomic, etc., (2) homoatomic or heteroatomic, and (3) representing an element or a compound.

(a)

(b)

(c)

(d)

Answers: a. diatomic (two atoms); heteroatomic (two kinds of atoms); compound (two kinds of atoms); b. diatomic (two atoms); homoatomic (one kind of atom); element (one kind of atom); c. triatomic (three atoms); heteroatomic (two kinds of atoms); compound (two kinds of atoms); d. tetraatomic (four atoms); heteroatomic (three kinds of atoms); compound (three kinds of atoms)

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1.10 Chemical Formulas

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1.10 CHEMICAL FORMULAS

B

F

Further information about the use of parentheses in chemical formulas (when and why) will be presented in Section 4.11. The important concern now is being able to interpret chemical formulas that contain parentheses in terms of total atoms present.

EXAMPLE 1.5 Inntteerp rpreeti tingg Chem Ch emiccaall Foorrmu mulas laas

Information about compound composition can be presented in a concise way by using a chemical formula. A chemical formula is a notation made up of the chemical symbols of the elements present in a compound and numerical subscripts (located to the right of each chemical symbol) that indicate the number of atoms of each element present in a molecule of the compound. The chemical formula for the compound aspirin is C9H8O4. This chemical formula conveys the information that an aspirin molecule contains three different elements— carbon (C), hydrogen (H), and oxygen (O)—and 21 atoms—9 carbon atoms, 8 hydrogen atoms, and 4 oxygen atoms. When only one atom of a particular element is present in a molecule of a compound, that element’s symbol is written without a numerical subscript in the formula for the compound. The formula for rubbing alcohol, C3H8O, reflects this practice for the element oxygen. In order to write formulas correctly, one must follow the capitalization rules for elemental symbols (Section 1.8). Making the error of capitalizing the second letter of an element’s symbol can dramatically alter the meaning of a chemical formula. The formulas CoCl2 and COCl2 illustrate this point; the symbol Co stands for the element cobalt, whereas CO stands for one atom of carbon and one atom of oxygen. Sometimes chemical formulas contain parentheses; an example is Al2(SO4)3. The interpretation of this formula is straightforward; in a formula unit, there are present 2 aluminum (Al) atoms and 3 SO4 groups. The subscript following the parentheses always indicates the number of units in the formula of the polyatomic entity inside the parentheses. In terms of atoms, the formula Al2(SO4)3 denotes 2 aluminum (Al) atoms, 3 ⫻ 1 ⫽ 3 sulfur (S) atoms, and 3 ⫻ 4 ⫽ 12 oxygen (O) atoms. Example 1.5 contains further comments about chemical formulas that contain parentheses.

For each of the following chemical formulas, determine how many atoms of each element are present in one molecule of the compound. a. HCN—hydrogen cyanide, a poisonous gas b. C18H21NO3—codeine, a pain-killing drug c. Ca10(PO4)6(OH)2—hydroxyapatite, present in tooth enamel Solution

a. One atom each of the elements hydrogen, carbon, and nitrogen is present. Remember that the subscript 1 is implied when no subscript is written. b. This formula indicates that 18 carbon atoms, 21 hydrogen atoms, 1 nitrogen atom, and 3 oxygen atoms are present in one molecule of the compound. c. There are 10 calcium atoms. The amounts of phosphorus, hydrogen, and oxygen are affected by the subscripts outside the parentheses. There are 6 phosphorus atoms and 2 hydrogen atoms present. Oxygen atoms are present in two locations in the formula. There are a total of 26 oxygen atoms: 24 from the PO4 subunits (6 ⫻ 4) and 2 from the OH subunits (2 ⫻ 1).

Practice Exercise 1.5 For each of the following chemical formulas, determine how many atoms of each element are present in one molecule of the compound. a. H2SO4—sulfuric acid, an industrial acid b. C17H20N4O6—riboflavin, a B vitamin c. Ca(NO3)2—calcium nitrate, used in fireworks to give a reddish color Answers: a. 2 hydrogen atoms, 1 sulfur atom, and 4 oxygen atoms; b. 17 carbon atoms, 20 hydrogen atoms, 4 nitrogen atoms, and 6 oxygen atoms; c. 1 calcium atom, 2 nitrogen atoms, and 6 oxygen atoms

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Chapter 1 Basic Concepts About Matter

ONCEPTS TO REMEMBER

Chemistry. Chemistry is the field of study that is concerned with the characteristics, composition, and transformations of matter (Section 1.1). Matter. Matter, the substances of the physical universe, is anything that has mass and occupies space. Matter exists in three physical states: solid, liquid, and gas (Section 1.2). Properties of matter. Properties, the distinguishing characteristics of a substance that are used in its identification and description, are of two types: physical and chemical. Physical properties are properties that can be observed without changing a substance into another substance. Chemical properties are properties that matter exhibits as it undergoes or resists changes in chemical composition. The failure of a substance to undergo change in the presence of another substance is considered a chemical property (Section 1.3). Changes in matter. Changes that can occur in matter are classified into two types: physical and chemical. A physical change is a process that does not alter the basic nature (chemical composition) of the substance under consideration. No new substances are ever formed as a result of a physical change. A chemical change is a process that involves a change in the basic nature (chemical composition) of the substance. Such changes always involve conversion of the material or materials under consideration into one or more new substances that have properties and composition distinctly different from those of the original materials (Section 1.4). Pure substances and mixtures. All specimens of matter are either pure substances or mixtures. A pure substance is a form of matter that has a definite and constant composition. A mixture is a physical combination of two or more pure substances in which the pure substances retain their identity (Section 1.5). Types of mixtures. Mixtures can be classified as heterogeneous or homogeneous on the basis of the visual recognition of the components present. A heterogeneous mixture contains visibly different parts or phases,

each of which has different properties. A homogeneous mixture contains only one phase, which has uniform properties throughout (Section 1.5). Types of pure substances. A pure substance can be classified as either an element or a compound on the basis of whether it can be broken down into two or more simpler substances by chemical means. Elements cannot be broken down into simpler substances. Compounds yield two or more simpler substances when broken down. There are 117 pure substances that qualify as elements. There are millions of compounds (Section 1.6). Chemical symbols. Chemical symbols are a shorthand notation for the names of the elements. Most consist of two letters; a few involve a single letter. The first letter of a chemical symbol is always capitalized, and the second letter is always lowercase (Section 1.8). Atoms and molecules. An atom is the smallest particle of an element that can exist and still have the properties of the element. Free isolated atoms are rarely encountered in nature. Instead, atoms are almost always found together in aggregates or clusters. A molecule is a group of two or more atoms that functions as a unit because the atoms are tightly bound together (Section 1.9). Types of molecules. Molecules are of two types: homoatomic and heteroatomic. Homoatomic molecules are molecules in which all atoms present are of the same kind. A pure substance containing homoatomic molecules is an element. Heteroatomic molecules are molecules in which two or more different kinds of atoms are present. Pure substances that contain heteroatomic molecules must be compounds (Section 1.9). Chemical formulas. Chemical formulas are used to specify compound composition in a concise manner. They consist of the symbols of the elements present in the compound and numerical subscripts (located to the right of each symbol) that indicate the number of atoms of each element present in a molecule of the compound (Section 1.10).

EXERC IS ES an d PROB LEM S The members of each pair of problems in this section test similar material. Chemistry: The Study of Matter (Section 1.1) 1.1 What are the two general characteristics that all types of matter possess? 1.2 What are the three aspects of matter that are of particular interest to chemists? 1.3

1.4

Classify each of the following as matter or energy (nonmatter). a. Air b. Pizza c. Sound d. Light e. Gold f. Virus Classify each of the following as matter or energy (nonmatter). a. Electricity b. Bacteria c. Silver d. Cake e. Water f. Magnetism

Physical States of Matter (Section 1.2) Give a characteristic that distinguishes a. liquids from solids b. gases from liquids 1.6 Give a characteristic that is the same for a. liquids and solids b. gases and liquids 1.5

1.7

Indicate whether each of the following substances does or does not take the shape of its container and also whether it has a definite volume.

1.8

a. Copper wire b. Oxygen gas c. Granulated sugar d. Liquid water Indicate whether each of the following substances does or does not take the shape of its container and also whether it has an indefinite volume. a. Aluminum powder b. Carbon dioxide gas c. Clean air d. Gasoline

Properties of Matter (Section 1.3) The following are properties of the substance magnesium. Classify each property as physical or chemical. a. Solid at room temperature b. Ignites upon heating in air c. Hydrogen gas is produced when it is dissolved in acids d. Has a density of 1.738 g/cm3 at 20°C 1.10 The following are properties of the substance magnesium. Clasify each property as physical or chemical. a. Silvery-white in color b. Does not react with cold water c. Melts at 651°C d. Finely divided form burns in oxygen with a dazzling white flame 1.9

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Exercises and Problems

1.11 Indicate whether each of the following statements describes a

physical or a chemical property. a. Silver salts discolor the skin by reacting with skin protein. b. Hemoglobin molecules have a red color. c. Beryllium metal vapor is extremely toxic to humans. d. Aspirin tablets can be pulverized with a hammer. 1.12 Indicate whether each of the following statements describes a physical or a chemical property. a. Diamonds are very hard substances. b. Gold metal does not react with nitric acid. c. Lithium metal is light enough to float on water. d. Mercury is a liquid at room temperature. Changes in Matter (Section 1.4) 1.13 Classify each of the following changes as physical or

chemical. a. Crushing a dry leaf b. Hammering a metal into a thin sheet c. Burning your chemistry textbook d. Slicing a ham 1.14 Classify each of the following changes as physical or chemical. a. Evaporation of water from a lake b. “Scabbing over” of a skin cut c. Cutting a string into two pieces d. Melting of some candle wax 1.15 Classify each of the following changes as physical or chemical.

a. A match burns b. “Rubbing alcohol” evaporates c. A copper object turns green over time d. A pan of water boils 1.16 Classify each of the following changes as physical or chemical. a. A newspaper page turns yellow over time b. A rubber band breaks c. A firecracker explodes d. Dry ice “disappears” over time 1.17 Correctly complete each of the following sentences by placing

the word chemical or physical in the blank. a. The freezing over of a pond’s surface is a ________ process. b. The crushing of some ice to make ice chips is a ________ procedure. c. The destruction of a newspaper through burning it is a ________ process. d. Pulverizing a hard sugar cube using a mallet is a ________ procedure. 1.18 Correctly complete each of the following sentences by placing the word chemical or physical in the blank. a. The reflection of light by a shiny metallic object is a ________ process. b. The heating of a blue powdered material to produce a white glassy-type substance and a gas is a ________ procedure. c. A burning candle produces light by ________ means. d. The grating of a piece of cheese is a ________ technique. Pure Substances and Mixtures (Section 1.5) 1.19 Classify each of the following statements as true or false.

a. All heterogeneous mixtures must contain three or more substances. b. Pure substances cannot have a variable composition. c. Substances maintain their identity in a heterogeneous mixture but not in a homogeneous mixture. d. Pure substances are seldom encountered in the “everyday” world.

17

1.20 Classify each of the following statements as true or false.

a. All homogeneous mixtures must contain at least two substances. b. Heterogeneous mixtures, but not homogeneous mixtures, can have a variable composition. c. Pure substances cannot be separated into other kinds of matter by physical means. d. The number of known pure substances is less than 100,000. 1.21 Assign each of the following descriptions of matter to one of

the following categories: heterogeneous mixture, homogeneous mixture, or pure substance. a. Two substances present, two phases present b. Two substances present, one phase present c. One substance present, two phases present d. Three substances present, three phases present 1.22 Assign each of the following descriptions of matter to one of the following categories: heterogeneous mixture, homogeneous mixture, or pure substance. a. Three substances present, one phase present b. One substance present, three phases present c. One substance present, one phase present d. Two substances present, three phases present 1.23 Classify each of the following as a heterogeneous mixture, a

homogeneous mixture, or a pure substance. Also indicate how many phases are present, assuming all components are present in the same container. a. Water and dissolved salt b. Water and sand c. Water, ice, and oil d. Carbonated water (soda water) and ice 1.24 Classify each of the following as a heterogeneous mixture, a homogeneous mixture, or a pure substance. Also indicate how many phases are present, assuming all components are present in the same container. a. Water and dissolved sugar b. Water and oil c. Water, wax, and pieces of copper metal d. Salt water and sugar water Elements and Compounds (Section 1.6) 1.25 From the information given, classify each of the pure substances

A through D as elements or compounds, or indicate that no such classification is possible because of insufficient information. a. Analysis with an elaborate instrument indicates that substance A contains two elements. b. Substance B decomposes upon heating. c. Heating substance C to 1000°C causes no change in it. d. Heating substance D to 500°C causes it to change from a solid to a liquid. 1.26 From the information given, classify each of the pure substances A through D as elements or compounds, or indicate that no such classification is possible because of insufficient information. a. Substance A cannot be broken down into simpler substances by chemical means. b. Substance B cannot be broken down into simpler substances by physical means. c. Substance C readily dissolves in water. d. Substance D readily reacts with the element chlorine. 1.27 From the information given in the following equations, classify

each of the pure substances A through G as elements or compounds, or indicate that no such classification is possible because of insufficient information. a. A ⫹ B : C b. D : E ⫹ F ⫹ G

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Chapter 1 Basic Concepts About Matter

1.28 From the information given in the following equations, classify

each of the pure substances A through G as elements or compounds, or indicate that no such classification is possible because of insufficient information. a. A : B ⫹ C b. D ⫹ E : F ⫹ G 1.29 Indicate whether each of the following statements is true or false.

a. Both elements and compounds are pure substances. b. A compound results from the physical combination of two or more elements. c. In order for matter to be heterogeneous, at least two compounds must be present. d. Compounds, but not elements, can have a variable composition. 1.30 Indicate whether each of the following statements is true or false. a. Compounds can be separated into their constituent elements by chemical means. b. Elements can be separated into their constituent compounds by physical means. c. A compound must contain at least two elements. d. A compound is a physical mixture of different elements. Discovery and Abundance of the Elements (Section 1.7) 1.31 Indicate whether each of the following statements about elements is true or false. a. Elements that do not occur in nature have been produced in a laboratory setting. b. At present 108 elements are known. c. Current chemical theory suggests there are more naturally occurring elements yet to be discovered. d. More laboratory-produced elements exist than naturally occuring elements. 1.32 Indicate whether each of the following statements about elements is true or false. a. The majority of the known elements have been discovered since 1990. b. New naturally occuring elements have been identified within the past 10 years. c. More than 25 laboratory-produced elements are known. d. All laboratory-produced elements are unstable. 1.33 Indicate whether each of the following statements about ele-

mental abundances is true or false. a. Silicon is the second most abundant element in Earth's crust. b. Hydrogen is the most abundant element in the universe but not in Earth’s crust. c. Oxygen and hydrogen are the two most abundant elements in the universe. d. One element accounts for over one-half of the atoms in Earth’s crust. 1.34 Indicate whether each of the following statements about elemental abundances is true or false. a. Hydrogen is the most abundant element in both Earth’s crust and the universe. b. Oxygen and silicon are the two most abundant elements in the universe. c. Helium is the second most abundant element in Earth’s crust. d. Two elements account for over three-fourths of the atoms in Earth’s crust. 1.35 With the help of Figure 1.10 indicate whether the first listed ele-

ment in each of the given pairs of elements is more abundant or

less abundant in Earth’s crust, in terms of atom percent, than the second listed element. a. Silicon and aluminum b. Calcium and hydrogen c. Iron and oxygen d. Sodium and potassium 1.36 With the help of Figure 1.10 indicate whether the first listed element in each of the given pairs of elements is more abundant or less abundant in Earth’s crust, in terms of atom percent, than the second listed element. a. Oxygen and hydrogen b. Iron and aluminum c. Calcium and magnesium d. Copper and sodium Names and Chemical Symbols of the Elements (Section 1.8) 1.37 Give the name of the element denoted by each of the following

chemical symbols. a. N b. Ni c. Pb d. Sn 1.38 Give the name of the element denoted by each of the following chemical symbols. a. Li b. He c. F d. Zn 1.39 Give the chemical symbol for each of the following elements.

a. Aluminum b. Neon c. Hydrogen d. Uranium 1.40 Give the chemical symbol for each of the following elements. a. Mercury b. Chlorine c. Gold d. Beryllium 1.41 Write the chemical symbol for each member of the following

pairs of elements. a. Sodium and sulfur b. Magnesium and manganese c. Calcium and cadmium d. Arsenic and argon 1.42 Write the chemical symbol for each member of the following pairs of elements. a. Copper and cobalt b. Potassium and phosphorus c. Iron and iodine d. Silicon and silver 1.43 In which of the following sequences of elements do all the ele-

ments have two-letter symbols? a. Magnesium, nitrogen, phosphorus b. Bromine, iron, calcium c. Aluminum, copper, chlorine d. Boron, barium, beryllium 1.44 In which of the following sequences of elements do all the elements have symbols that start with a letter that is not the first letter of the element’s English name? a. Silver, gold, mercury b. Copper, helium, neon c. Cobalt, chromium, sodium d. Potassium, iron, lead Atoms and Molecules (Section 1.9) 1.45 Classify the substances represented by the following models as

homoatomic or heteroatomic molecules. a. b. O O C O O H H c.

d. O O

C

O

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Exercises and Problems

1.46 Classify the substances represented by the following models as

homoatomic or heteroatomic molecules. a. b. H O H H O O C

19

c. A molecule that is triatomic and contains three elements d. A molecule that is triatomic, is not symmetrical, and contains two kinds of atoms Chemical Formulas (Section 1.10) 1.55 Write chemical formulas for the substances represented by the

H

molecular models given in Problem 1.45. c.

d. O

H O

H

H C

H H

1.56 Write chemical formulas for the substances represented by the

molecular models given in Problem 1.46.

C H

1.47 Classify the substances represented by the models in Problem

1.45 as to the number of atoms present per molecule, that is, as diatomic, triatomic, tetraatomic, etc. 1.48 Classify the substances represented by the models in Problem 1.46 as to the number of atoms present per molecule, that is, as diatomic, triatomic, tetraatomic, etc. 1.49 Classify the substances represented by the models in Problem

1.45 as to type of pure substance, that is, as element or compound. 1.50 Classify the substances represented by the models in Problem 1.46 as to type of pure substance, that is, as element or compound. 1.51 Indicate whether each of the following statements is true or

false. If a statement is false, change it to make it true. (Such a rewriting should involve more than merely converting the statement to the negative of itself.) a. The atom is the limit of chemical subdivision for both elements and compounds. b. Triatomic molecules must contain at least two kinds of atoms. c. A molecule of a compound must be heteroatomic. d. Only heteroatomic molecules may contain three or more atoms. 1.52 Indicate whether each of the following statements is true or false. If a statement is false, change it to make it true. (Such a rewriting should involve more than merely converting the statement to the negative of itself.) a. A molecule of an element may be homoatomic or heteroatomic, depending on which element is involved. b. The limit of chemical subdivision for a compound is a molecule. c. Heteroatomic molecules do not maintain the properties of their constituent elements. d. Only one kind of atom may be present in a homoatomic molecule. 1.53 Draw a diagram of each of the following molecules using

circular symbols of your choice to represent atoms. a. A diatomic molecule of a compound b. A molecule that is triatomic and homoatomic c. A molecule that is tetraatomic and contains three kinds of atoms d. A molecule that is triatomic, is symmetrical, and contains two elements 1.54 Draw a diagram of each of the following molecules using circular symbols of your choice to represent atoms. a. A triatomic molecule of an element b. A molecule that is diatomic and heteroatomic

1.57 On the basis of its chemical formula, classify each of the fol-

lowing substances as an element or a compound. b. CO c. Co d. S8 a. LiClO3 1.58 On the basis of its chemical formula, classify each of the following substances as an element or a compound. b. COCl2 c. SN d. Sn a. CoCl2 1.59 List the element(s) present in each of the substances whose

chemical formulas were given in Problem 1.57. 1.60 List the element(s) present in each of the substances whose

chemical formulas were given in Problem 1.58. 1.61 Write chemical formulas for compounds in which the combin-

ing ratios of atoms are as follows: a. Table sugar: carbon:hydrogen:oxygen, 12:22:11 b. Caffeine: carbon:hydrogen:nitrogen:oxygen, 8:10:4:2 1.62 Write chemical formulas for compounds in which the combining ratios of atoms are as follows: a. Vitamin C: carbon:hydrogen:oxygen, 6:8:6 b. Nicotine: carbon:hydrogen:nitrogen, 10:14:2 1.63 Write a chemical formula for each of the following substances

based on the information given about a molecule of the substance. a. A molecule of hydrogen cyanide is triatomic and contains the elements hydrogen, carbon, and nitrogen. b. A molecule of sulfuric acid is heptaatomic and contains two atoms of hydrogen, one atom of sulfur, and the element oxygen. 1.64 Write a chemical formula for each of the following substances based on the information given about a molecule of the substance. a. A molecule of nitrous oxide contains twice as many atoms of nitrogen as of oxygen and is triatomic. b. A molecule of nitric acid is pentaatomic and contains three atoms of oxygen and the elements hydrogen and nitrogen. 1.65 Write chemical formulas for the following compounds by using

the given “verbally transmitted” information. a. BA (pause) CL2 b. H (pause) N (pause) O3 c. NA3 (pause) P (pause) O4 d. MG (pause) OH taken twice 1.66 Write chemical formulas for the following compounds by using the given “verbally transmitted” information. a. NA (pause) BR b. H2 (pause) S (pause) O4 c. ZN (pause) CL2 d. FE (pause) CN taken three times

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Chapter 1 Basic Concepts About Matter

A DD D I TION AL P R O BL L EMS 1.67 In the following diagrams, the different colored spheres repre-

sent atoms of different elements.

I

II

III

IV

Select the diagram or diagrams that represent each of the listed situations. (Note that there may be more than one correct answer for a given situation and that answers may be used more than once or not at all.) a. Which diagram(s) represent(s) a compound whose molecules are triatomic? b. Which diagram(s) represent(s) a mixture of two compounds? c. Which diagram(s) represent(s) a mixture that contains two different types of diatomic molecules? d. Which diagram(s) represent(s) a pure substance? 1.68 In the following diagrams, different colored spheres represent atoms of different elements.

c. A green solid, all of which melts at the same temperature to produce a liquid that decomposes upon further heating d. A colorless gas that cannot be separated into simpler substances using physical means and that reacts with copper to produce both a copper-nitrogen compound and a copperoxygen compound 1.71 Assign each of the following descriptions of matter to one of the following categories: element, compound, or mixture. a. One substance present, one phase present, one kind of homoatomic molecule present b. Two substances present, two phases present, all molecules are heteroatomic c. One phase present, two kinds of homoatomic molecules present d. One phase present, all molecules are triatomic, all molecules are heteroatomic, all molecules are identical 1.72 In the following diagram, the different colored spheres represent atoms of different elements. Four changes, denoted by the four numbered arrows, are shown.

1

2

3

I

II

III

4

IV

Select the diagram or diagrams that represent each of the listed situations. (Note that there may be more than one correct answer for a given situation and that answers may be used more than once or not at all.) a. Which diagram(s) represent(s) a compound whose molecules are tetraatomic? b. Which diagram(s) represent(s) a mixture of two substances? c. Which diagram(s) represent(s) a mixture of two elements? d. Which diagram(s) represent(s) a pure substance? 1.69 Assign each of the following descriptions of matter to one of the following categories: element, compound, or mixture. a. One substance present, one phase present, substance cannot be decomposed by chemical means b. One substance present, three elements present c. Two substances present, two phases present d. Two elements present, composition is definite and constant 1.70 Indicate whether each of the following samples of matter is a heterogeneous mixture, a homogeneous mixture, a compound, or an element. a. A colorless gas, only part of which reacts with hot iron b. A “cloudy” liquid that separates into two layers upon standing for two hours

Select the change, by listing the arrow number, that represents each of the listed situations. (Note that there may be more than one correct answer for a given situation and that answers may be used more than once or not at all.) a. Which change(s) is a (are) physical change(s)? b. Which change(s) is a (are) chemical change(s)? c. Which change(s) is a (are) change(s) in which a compound is decomposed into its constituent elements? d. Which change(s) is a (are) change(s) in which two elements combine to form a compound? 1.73 Certain words can be viewed whimsically as sequential combinations of symbols of elements. For example, the given name Stephen is made up of the following sequence of chemical symbols: S-Te-P-He-N. Analyze each of the following given names in a similar manner. a. Barbara b. Eugene c. Heather d. Allan 1.74 In each of the following pairs of chemical formulas, indicate whether the first chemical formula listed denotes more total atoms, the same number of total atoms, or fewer total atoms than the second chemical formula listed.

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Multiple-Choice Practice Test

a. HN3 and NH3 b. CaSO4 and Mg(OH)2 c. NaClO3 and Be(CN)2 d. Be3(PO4)2 and Mg(C2H3O2)2 1.75 On the basis of the given information, determine the numerical value of the subscript x in each of the following chemical formulas. a. BaS2Ox: formula unit contains 6 atoms b. Al2(SOx)3; formula unit contains 17 atoms c. SOxClx; formula unit contains 5 atoms d. CxH2xClx; formula unit contains 8 atoms

1.76 A mixture contains the following five pure substances: N2, N2H4,

NH3, CH4, and CH3Cl. a. How many different kinds of molecules that contain four or fewer atoms are present in the mixture? b. How many different kinds of atoms are present in the mixture? c. How many total atoms are present in a mixture sample containing five molecules of each component? d. How many total hydrogen atoms are present in a mixture sample containing four molecules of each component?

multiple-Choice Practice Test Which of the following is a property of both liquids and solids? a. Definite shape b. Definite volume c. Indefinite shape d. Indefinite volume 1.78 In which of the following pairs of properties are both of the properties physical properties? a. Freezes at 10°C, red in color b. Decomposes at 75°C, reacts with oxygen c. Good conductor of electricity, flammable d. Has a low density, nonflammable 1.79 Which of the following is always a characteristic of a chemical change? a. Heat is absorbed. b. Light is emitted. c. One or more new substances are produced. d. A change of state occurs. 1.80 Which of the following statements is incorrect? a. Some, but not all, pure substances contain homoatomic molecules. b. Some, but not all, pure substances contain heteroatomic molecules. c. Some, but not all, compounds are pure substances. d. Some, but not all, compounds contain three or more elements. 1.81 A pure substance A is found to change upon heating into two new pure substances B and C. Substance B, but not substance C, undergoes reaction with oxygen. Based on this information we definitely know that a. A is a compound and C is an element. b. Both A and B are compounds. c. B is a compound and C is an element. d. A is a compound. 1.77

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1.82 In which of the following listings of elements do each of the

1.83

1.84

1.85

1.86

elements have a two-letter chemical symbol? a. Tin, nitrogen, zinc b. Potassium, fluorine, carbon c. Lead, hydrogen, iodine d. Magnesium, silicon, chlorine Which of the following statements concerning elemental abundances is incorrect? a. One element accounts for over one-half of all atoms present in Earth’s crust. b. Two elements account for over three-fourths of all atoms present in Earth’s crust. c. Elemental abundances in Earth’s crust closely parallel elemental abundances in the universe as a whole. d. Hydrogen is the most abundant type of atom in the universe as a whole. Which of the following pairings of terms is incorrect? a. Element—a single type of atom b. Pure substance—variable composition c. Heterogeneous mixture—two or more regions with different properties d. Compound—two or more elements present Which of the following classifications of matter could not contain molecules that are both heteroatomic and diatomic? a. Heterogeneous mixture b. Homogeneous mixture c. Compound d. Element In which of the following pairs of chemical formulas do the two members of the pair contain the same number of atoms per molecule? b. CoCl2 and COCl2 a. NaSCN and H2CO3 c. H3N and HN3 d. Mg(OH)2 and SO3

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Measurements in Chemistry Chapter Outline 2.1 Measurement Systems 22 2.2 Metric System Units 23 2.3 Exact and Inexact Numbers 26

2

2.4 Uncertainty in Measurement and Significant Figures 26

CHEMISTRY AT A GLANCE: Significant Figures 28 2.5 Significant Figures and Mathematical Operations 28 2.6 Scientific Notation 32 2.7 Conversion Factors 34 2.8 Dimensional Analysis 36

CHEMISTRY AT A GLANCE: Conversion Factors 38 2.9 Density 39 2.10 Temperature Scales 41 2.11 Heat Energy and Specific Heat 43

CHEMICAL CONNECTIONS Body Density and Percent Body Fat 40 Normal Human Body Temperature 44

Measurements can never be exact; there is always some degree of uncertainty.

I

t would be extremely difficult for a carpenter to build cabinets without being able to use tools such as hammers, saws, drills, tape measures, rulers, straight edges, and T-squares. They are the tools of a carpenter’s trade. Chemists also have “tools of the trade.” The tool they use most is called measurement. Understanding measurement is indispensable in the study of chemistry. Questions such as “How much . . . ?,” “How long . . . ?,” and “How many . . . ?” simply cannot be answered without resorting to measurements. This chapter will help you learn what you need to know to deal properly with measurement. Much of the material in the chapter is mathematical. This is necessary; measurements require the use of numbers.

2.1 MEASUREMENT SYSTEMS

The word metric is derived from the Greek word metron, which means “measure.”

22

We all make measurements on a routine basis. For example, measurements are involved in following a recipe for making brownies, in determining our height and weight, and in fueling a car with gasoline. Measurement is the determination of the dimensions, capacity, quantity, or extent of something. In chemical laboratories, the most common types of measurements are those of mass, volume, length, time, temperature, pressure, and concentration. Two systems of measurement are in use in the United States: (1) the English system of units and (2) the metric system of units. Common measurements of commerce, such as those used in a grocery store, are made in the English system. The units of this system include the inch, foot, pound, quart, and gallon. The metric system is used in scientific work. The units of this system include the gram, meter, and liter.

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The United States is in the process of voluntary conversion to the metric system for measurements of commerce. Metric system units now appear on numerous consumer products. Soft drinks now come in 1-, 2-, and 3-liter containers. Road signs in some states display distances in both miles and kilometers (Figure 2.1). Canned and packaged goods such as cereals and mixes on grocery store shelves now have the masses of their contents listed in grams as well as in pounds and ounces. The metric system is superior to the English system. Its superiority stems from the interrelationships between units of the same type (volume, length, etc.). Metric unit interrelationships are less complicated than English unit interrelationships because the metric system is a decimal unit system. In the metric system, conversion from one unit size to another can be accomplished simply by moving the decimal point to the right or left an appropriate number of places. Thus, the metric system is simply more convenient to use.

2.2 METRIC SYSTEM UNITS Figure 2.1 Metric system units are becoming increasingly evident on highway signs.

The modern version of the metric system is called the International System, or SI (the abbreviation is taken from the French name, le Système International).

EXAMPLE 2.1 Recognizing the Mathematical Meanings of Metric System Prefixes

In the metric system, there is one base unit for each type of measurement (length, mass, volume, and so on). The names of fractional parts of the base unit and multiples of the base unit are constructed by adding prefixes to the base unit. These prefixes indicate the size of the unit relative to the base unit. Table 2.1 lists common metric system prefixes, along with their symbols or abbreviations and mathematical meanings. The prefixes in color are the ones most frequently used. The meaning of a metric system prefix is independent of the base unit it modifies and always remains constant. For example, the prefix kilo- always means 1000; a kilosecond is 1000 seconds, a kilowatt is 1000 watts, and a kilocalorie is 1000 calories. Similarly, the prefix nano- always means one-billionth; a nanometer is one-billionth of a meter, a nanogram is one-billionth of a gram, and a nanoliter is one-billionth of a liter.

Using Table 2.1, write the name of the metric system prefix associated with the listed power of 10 or the power of 10 associated with the listed metric system prefix. a. nano-

b. micro-

c. deci-

d. 103

e. 106

f. 109

Solution The use of numerical prefixes should not be new to you. Consider the use of the prefix tri- in the words triangle, tricycle, trio, trinity, and triple. Each of these words conveys the idea of three of something. The metric system prefixes are used in the same way.

a. b. c. d. e. f.

The prefix nano- denotes 10⫺9 (one-billionth). The prefix micro- denotes 10⫺6 (one-millionth). The prefix deci- denotes 10⫺1 (one-tenth). 103 (one thousand) is denoted by the prefix kilo-. 106 (one million) is denoted by the prefix mega-. 109 (one billion) is denoted by the prefix giga-.

Practice Exercise 2.1 Using Table 2.1, write the name of the metric system prefix associated with the listed power of 10 or the power of 10 associated with the listed metric system prefix. a. milli-

b. pico-

c. mega-

d. 10⫺6

e. 10⫺2

f. 10⫺1

Answers: a. 10⫺3; b. 10⫺12; c. 106; d. micro-; e. centi-; f. deci-

Metric Length Units

Length is measured by determining the distance between two points.

The meter (m) is the base unit of length in the metric system. It is about the same size as the English yard; 1 meter equals 1.09 yards (Figure 2.2a). The prefixes listed in Table 2.1 enable us to derive other units of length from the meter. The kilometer (km) is 1000 times larger than the meter; the centimeter (cm) and millimeter (mm) are, respectively, one-hundredth

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Chapter 2 Measurements in Chemistry

TABLE 2.1 Common Metric System Prefixes with Their Symbols and Mathematical Meanings

Prefix*

Symbol

Mathematical Meaning†

Multiples

gigamegakilo-

G M k

1,000,000,000 (109, billion) 1,000,000 (106, million) 1000 (103, thousand)

Fractional Parts

decicentimillimicronanopico-

d c m  (Greek mu) n p

0.1 (101, one-tenth) 0.01 (102, one-hundredth) 0.001 (103, one-thousandth) 0.000001 (106, one-millionth) 0.000000001 (109, one-billionth) 0.000000000001 (1012, one-trillionth)

*Other prefixes also are available but are less commonly used. †The power-of-10 notation for denoting numbers is considered in Section 2.6.

and one-thousandth of a meter. Most laboratory length measurements are made in centimeters rather than meters because of the meter’s relatively large size.

Metric Mass Units Mass is measured by determining the amount of matter in an object.

Students often erroneously think that the terms mass and weight have the same meaning. Mass is a measure of the amount of material present in a sample. Weight is a measure of the force exerted on an object by the pull of gravity.

Figure 2.2 Comparisons of the base metric system units of length (meter), mass (gram), and volume (liter) with common objects.

The gram (g) is the base unit of mass in the metric system. It is a very small unit compared with the English ounce and pound (Figure 2.2b). It takes approximately 28 grams to equal 1 ounce and nearly 454 grams to equal 1 pound. Both grams and milligrams (mg) are commonly used in the laboratory, where the kilogram (kg) is generally too large. The terms mass and weight are often used interchangeably in measurement discussions; technically, however, they have different meanings. Mass is a measure of the total quantity of matter in an object. Weight is a measure of the force exerted on an object by gravitational forces. The mass of a substance is a constant; the weight of an object varies with the object’s geographical location. For example, matter weighs less at the equator than it would at the North Pole because the pull of gravity is less at the equator. Because Earth is not a perfect sphere, but bulges at the equator, the magnitude of gravitational attraction is less at the equator. An object would weigh less on the moon than on Earth because of the smaller

(a) Length

(b) Mass

(c) Volume

A meter is slightly larger than a yard.

A gram is a small unit compared to a pound.

A liter is slightly larger than a quart.

1 meter = 1.09 yards.

1 gram = 1/454 pound.

1 liter = 1.06 quarts.

A baseball bat is about 1 meter long.

Two pennies, five paperclips, and a marble have masses of about 5, 2, and 5 grams, respectively.

Most beverages are now sold by the liter rather than by the quart.

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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2.2 Metric System Units

Volume is measured by determining the amount of space occupied by a three-dimensional object.

25

size of the moon and the correspondingly lower gravitational attraction. Quantitatively, a 22.0-lb mass weighing 22.0 lb at Earth’s North Pole would weigh 21.9 lb at Earth’s equator and only 3.7 lb on the moon. In outer space, an astronaut may be weightless but never massless. In fact, he or she has the same mass in space as on Earth.

Metric Volume Units

Total volume of large cube = 1000 cm3 = 1 L

The liter (L) is the base unit of volume in the metric system. The abbreviation for liter is a capital L rather than a lower-case l because a lower-case l is easily confused with the number 1. A liter is a volume equal to that occupied by a cube that is 10 centimeters on each side. Because the volume of a cube is calculated by multiplying length times width times height (which are all the same for a cube), we have 1 liter  volume of a cube with 10 cm edges  10 cm  10 cm  10 cm  1000 cm3

10 9 8 7 6 5 4 3 2 1

1 cm3 = 1 mL

A liter is also equal to 1000 milliliters; the prefix milli- means one-thousandth. Therefore, 1000 mL  1000 cm3

Figure 2.3 A cube 10 cm on a side has a volume of 1000 cm3, which is equal to 1 L. A cube 1 cm on a side has a volume of 1 cm3, which is equal to 1 mL.

Another abbreviation for the unit cubic centimeter, used in medical situations, is cc. 1 cm3  1 cc

Figure 2.4 The use of the concentration unit milligrams per deciliter (mg/dL) is common in clinical laboratory reports dealing with the composition of human body fluids.

Dividing both sides of this equation by 1000 shows that 1 mL  1 cm3 Consequently, the units milliliter and cubic centimeter are the same. In practice, mL is used for volumes of liquids and gases, and cm3 for volumes of solids. Figure 2.3 shows the relationship between 1 mL (1 cm3) and its parent unit, the liter, in terms of cubic measurements. A liter and a quart have approximately the same volume; 1 liter equals 1.06 quarts (Figure 2.2c). The milliliter and deciliter (dL) are commonly used in the laboratory. Deciliter units are routinely encountered in clinical laboratory reports detailing the composition of body fluids (Figure 2.4). A deciliter is equal to 100 mL (0.100 L).

Healthy, I.M. M

37

9/23/07

9/23/07

05169

Your Doctor Anywhere, U.S.A.

000-00-000

Test Name

9/24/07

032136

Result

CHEM-SCREEN PROFILE CALCIUM 9.70 PHOSPHATE (as PHOSPHORUS) 3.00 BUN 16.00 CREATININE 1.30 BUN/CREAT RATIO 12.31 URIC ACID 7.50 GLUCOSE 114.00 TOTAL PROTEIN 7.90 ALBUMIN 5.10 GLOBULIN 2.80 ALB/GLOB RATIO 1.82 TOTAL BILIRUBIN 0.55 DIRECT BILIRUBIN 0.18 CHOLESTEROL 203.00 CHOLESTEROL PERCENTILE 50 HDL CHOLESTEROL 71 CHOL./HDL CHOLESTEROL *(01)-2.77 TRIGLYCERIDES 148.00

Units

mg/dL mg/dL mg/dL mg/dL mg/dL mg/dL g/dL g/dL g/dL mg/dL mg/dL mg/dL PERCENTILE mg/dL mg/dL

Normal Reference Range

9.00-10.40 2.20-4.30 9.00-23.0 0.80-1.30 12-20 3.60-8.30 65.0-130 6.50-8.00 3.90-4.90 2.10-3.50 1.20-2.20 0.30-1.40 0.04-0.20 140-233 1-74

50.0-200

(01) THE RESULT OBTAINED FOR THE CHOLESTEROL/HDL CHOLESTEROL RATIO FOR THIS PATIENT’S SAMPLE IS ASSOCIATED WITH THE LOWEST CORONARY HEART DISEASE (CHD) RISK.

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2.3 EXACT AND INEXACT NUMBERS

All measurements have some degree of uncertainty associated with them. Thus, the numerical value associated with a measurement is always an inexact number.

In scientific work, numbers are grouped in two categories: exact numbers and inexact numbers. An exact number is a number whose value has no uncertainty associated with it—that is, it is known exactly. Exact numbers occur in definitions (for example, there are exactly 12 objects in a dozen, not 12.01 or 12.02); in counting (for example, there can be 7 people in a room, but never 6.99 or 7.03); and in simple fractions (for example, 1/3, 3/5, and 5/9). An inexact number is a number whose value has a degree of uncertainty associated with it. Inexact numbers result any time a measurement is made. It is impossible to make an exact measurement; some uncertainty will always be present. Flaws in measuring device construction, improper calibration of an instrument, and the skills (or lack of skills) possessed by a person using a measuring device all contribute to error (uncertainty). Section 2.4 considers further the origins of the uncertainty associated with measurements and also the methods used to “keep track” of such uncertainty.

2.4 UNCERTAINTY IN MEASUREMENT AND SIGNIFICANT FIGURES As noted in the previous section, because of the limitations of the measuring device and the limited powers of observation of the individual making the measurement, every measurement carries a degree of uncertainty or error. Even when very elaborate measuring devices are used, some degree of uncertainty is always present.

Origin of Measurement Uncertainty Read as 3.7 cm 1

2

3

4

cm Ruler A

Read as 3.74 cm 1

2

3

4

cm Ruler B

Figure 2.5 The scale on a measuring device determines the magnitude of the uncertainty for the recorded measurement. Measurements made with ruler A will have greater uncertainty than those made with ruler B.

To illustrate how measurement uncertainty arises, let us consider how two different rulers, shown in Figure 2.5, are used to measure a given length. Using ruler A, we can say with certainty that the length of the object is between 3 and 4 centimeters. We can further say that the actual length is closer to 4 centimeters and estimate it to be 3.7 centimeters. Ruler B has more subdivisions on its scale than ruler A. It is marked off in tenths of a centimeter instead of in centimeters. Using ruler B, we can definitely say that the length of the object is between 3.7 and 3.8 centimeters and can estimate it to be 3.74 centimeters. Note how both length measurements (ruler A and ruler B) contain some digits (all those except the last one) that are exactly known and one digit (the last one) that is estimated. It is this last digit, the estimated one, that produces uncertainty in a measurement. Note also that the uncertainty in the second length measurement is less than that in the first one—an uncertainty in the hundredths place compared with an uncertainty in the tenths place. We say that the second measurement is more precise than the first one; that is, it has less uncertainty than the first measurement. Only one estimated digit is ever recorded as part of a measurement. It would be incorrect for a scientist to report that the length of the object in Figure 2.5 is 3.745 centimeters as read by using ruler B. The value 3.745 contains two estimated digits, the 4 and the 5, and indicates a measurement with less uncertainty than what is actually obtainable with that particular measuring device. Again, only one estimated digit is ever recorded as part of a measurement. Because measurements are never exact, two types of information must be conveyed whenever a numerical value for a measurement is recorded: (1) the magnitude of the measurement and (2) the uncertainty of the measurement. The magnitude is indicated by the digit values. Uncertainty is indicated by the number of significant figures recorded. Significant figures are the digits in a measurement that are known with certainty plus one digit that is estimated. To summarize, in equation form, Number of significant figures  all certain digits  one estimated digit

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Guidelines for Determining Significant Figures Recognizing the number of significant figures in a measured quantity is easy for measurements we make ourselves, because we know the type of instrument we are using and its limitations. However, when someone else makes the measurement, such information is often not available. In such cases, we follow a set of guidelines for determining the number of significant figures in a measured quantity. The term significant figures is often verbalized in shortened form as “sig figs.”

1. In any measurement, all nonzero digits are significant. 2. Zeros may or may not be significant because zeros can be used in two ways: (1) to position a decimal point and (2) to indicate a measured value. Zeros that perform the first function are not significant, and zeros that perform the second function are significant. When zeros are present in a measured number, we follow these rules: a. Leading zeros, those at the beginning of a number, are never significant. 0.0141 has three significant figures. 0.0000000048 has two significant figures. b. Confined zeros, those between nonzero digits, are always significant. 3.063 has four significant figures. 0.001004 has four significant figures. c. Trailing zeros, those at the end of a number, are significant if a decimal point is present in the number. 56.00 has four significant figures. 0.05050 has four significant figures. d. Trailing zeros, those at the end of a number, are not significant if the number lacks an explicitly shown decimal point. 59,000,000 has two significant figures. 6010 has three significant figures. It is important to remember what is “significant” about significant figures. The number of significant figures in a measurement conveys information about the uncertainty associated with the measurement. The “location” of the last significant digit in the numerical value of a measurement specifies the measurement’s uncertainty: Is this last significant digit located in the hundredths, tenths, ones, or tens position, etc.? Consider the following measurement values (with the last significant digit “boxed” for emphasis). 4620.0 (five significant figures) has an uncertainty of tenths. 4620 (three significant figures) has an uncertainty in the tens place. 462,000 (three significant figures) has an uncertainty in the thousands place. The Chemistry at a Glance feature on page 28 reviews the rules that govern which digits in a measurement are significant.

EXAMPLE 2.2 Determining the Number of Significant Figures in a Measurement and the Uncertainty Associated with the Measurement

For each of the following measurements, give the number of significant figures present and the uncertainty associated with the measurement. a. 5623.00

b. 0.0031

c. 97,200

d. 637

Solution

a. Six significant figures are present because trailing zeros are significant when a decimal point is present. The uncertainty is in the hundredths place (0.01), the location of the last significant digit. (continued)

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Chapter 2 Measurements in Chemistry

Significant Figures SIGNIFICANT FIGURES The digits in a measurement known with certainty plus one estimated digit.

Nonzero Digits

The Digit Zero

The digits 1, 2, 3, 4, 5, 6, 7, 8, and 9 are always significant.

Zeros may or may not be significant, depending on whether they mark the decimal point or indicate a measured value.

Leading Zeros

Confined Zeros

Trailing Zeros

Zeros located at the beginning of a number are NEVER significant.

Zeros located between nonzero digits are ALWAYS significant.

Zeros located at the end of a number are significant only if the number has an explicitly shown decimal point.

0.0070002000 Not significant

Significant

Significant because of decimal point

b. Two significant figures are present because leading zeros are never significant. The uncertainty is in the ten-thousandths place (⫾0.0001), the location of the last significant digit. c. Three significant figures are present because the trailing zeros are not significant (no explicit decimal point is shown). The uncertainty is in the hundreds place (⫾100). d. Three significant figures are present, and the uncertainty is in the ones place (⫾1).

Practice Exercise 2.2 For each of the following measurements, give the number of significant figures present and the uncertainty associated with the measurement. a. 727.23

b. 0.1031

c. 47,230

d. 637,000,000

Answers: a. 5, ⫾0.01; b. 4, ⫾0.0001; c. 4, ⫾10; d. 3, ⫾1,000,000

2.5 SIGNIFICANT FIGURES AND MATHEMATICAL OPERATIONS When measurements are added, subtracted, multiplied, or divided, consideration must be given to the number of significant figures in the computed result. Mathematical operations should not increase (or decrease) the uncertainty of experimental measurements.

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Hand-held electronic calculators generally “complicate” uncertainty considerations because they are not programmed to take significant figures into account. Consequently, the digital readouts display more digits than are warranted (Figure 2.6). It is a mistake to record these extra digits, because they are not significant figures and hence are meaningless.

Rounding Off Numbers When we obtain calculator answers that contain too many digits, it is necessary to delete (drop) the nonsignificant digits, a process that is called rounding off. Rounding off is the process of deleting unwanted (nonsignificant) digits from calculated numbers. There are two rules for rounding off numbers.

Figure 2.6 The digital readout on an electronic calculator usually shows more digits than are warranted. Calculators are not programmed to account for significant figures.

EXAMPLE 2.3 Rounding Numbers to a Specified Number of Significant Figures

1. If the first digit to be deleted is 4 or less, simply drop it and all the following digits. For example, the number 3.724567 becomes 3.72 when rounded to three significant figures. 2. If the first digit to be deleted is 5 or greater, that digit and all that follow are dropped, and the last retained digit is increased by one. The number 5.00673 becomes 5.01 when rounded to three significant figures. These rounding rules must be modified slightly when digits to the left of the decimal point are to be dropped. To maintain the inferred position of the decimal point in such situations, zeros must replace all the dropped digits that are to the left of the inferred decimal point. Parts (c) and (d) of Example 2.3 illustrate this point.

Round off each of the following numbers to two significant figures. a. 25.7

b. 0.4327

c. 432,117

d. 13,500

Solution

a. Rule 2 applies. The last retained digit (the 5) is increased in value by one unit. 25.7 becomes 26 b. Rule 1 applies. The last retained digit (the 3) remains the same, and all digits that follow it are simply dropped. 0.4327 becomes 0.43 c. Since the first digit to be dropped is a 2, rule 1 applies 432,117 becomes 430,000 Note that to maintain the position of the inferred decimal point, zeros must replace all of the dropped digits. This will always be the case when digits to the left of the inferred decimal place are dropped. d. This is a rule 2 situation because the first digit to be dropped is a 5. The 3 is rounded up to a 4 and zeros take the place of all digits to the left of the inferred decimal place that are dropped. 13,500 becomes 14,000

Practice Exercise 2.3 Round off each of the following numbers to three significant figures. a. 432.55

b. 0.03317

c. 162,700

d. 65,234

Answers: a. 433; b. 0.0332; c. 163,000; d. 65,200

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Operational Rules Significant-figure considerations in mathematical operations that involve measured numbers are governed by two rules, one for multiplication and division and one for addition and subtraction. 1. In multiplication and division, the number of significant figures in the answer is the same as the number of significant figures in the measurement that contains the fewest significant figures. For example, 4) glycosidic linkage.  ((1

CH2OH O

CH2OH O HO The  form of lactose is sweeter to the taste and more soluble in water than the b form. The b form can be found in ice cream that has been stored for a long time; it crystallizes and gives the ice cream a gritty texture.

4) Glycosidic linkage

O

OH

OH

OH OH OH  -D-Galactose

D-Glucose

Lactose

586

Chapter 18 Carbohydrates

The enzyme needed to break the (1 —> 4) linkage in lactose is different from the one needed to break the (1 —> 4) linkage in cellobiose. Because the two disaccharides have slightly different structures, different enzymes are required—lactase for lactose and cellobiase for cellobiose.

The glycosidic linkage in sucrose is very different from that in maltose, cellobiose, and lactose. The linkages in the latter three compounds can be characterized as “head-to-tail” linkages—that is, the front end (carbon 1) of one monosaccharide is linked to the back end (carbon 4) of the other monosaccharide. Sucrose has a “head-to-head” glycosidic linkage; the front ends of the two monosaccharides (carbon 1 for glucose and carbon 2 for fructose) are linked.

B

F

The term invert sugar comes from the observation that the direction of rotation of plane-polarized light (Section 18.7) changes from positive (clockwise) to negative (counterclockwise) when sucrose is hydrolyzed to invert sugar. The rotation is 66 for sucrose. The net rotation for the invert sugar mixture of fructose (92) and glucose (52) is 40.

The glucose hemiacetal center is unaffected when galactose bonds to glucose in the formation of lactose, so lactose is a reducing sugar (the glucose ring can open to give an aldehyde). Lactose is the major sugar found in milk. This accounts for its common name, milk sugar. Enzymes in mammalian mammary glands take glucose from the bloodstream and synthesize lactose in a four-step process. Epimerization (Section 18.6) of glucose yields galactose, and then the (1 —> 4) linkage forms between a galactose and a glucose unit. Lactose is an important ingredient in commercially produced infant formulas that are designed to simulate mother’s milk. Souring of milk is caused by the conversion of lactose to lactic acid by bacteria in the milk. Pasteurization of milk is a quick-heating process that kills most of the bacteria and retards the souring process. Lactose can be hydrolyzed by acid or by the enzyme lactase, forming an equimolar mixture of galactose and glucose. D-Lactose  H2O

+

H or lactase 88888888n D-galactose  D-glucose

In the human body, the galactose so produced is then converted to glucose by other enzymes. The genetic condition lactose intolerance, an inability of the human digestive system to hydrolyze lactose, is considered in the Chemical Connections feature on page 585.

Sucrose Sucrose, common table sugar, is the most abundant of all disaccharides and occurs throughout the plant kingdom. It is produced commercially from the juice of sugar cane and sugar beets. Sugar cane contains up to 20% by mass sucrose, and sugar beets contain up to 17% by mass sucrose. Figure 18.20 shows a molecular model for sucrose. The two monosaccharide units present in a D-sucrose molecule are -D-glucose and b-D-fructose. The glycosidic linkage is not a (1 —> 4) linkage, as was the case for maltose, cellobiose, and lactose. It is instead an a, b(1 —> 2) glycosidic linkage. The —OH group on carbon 2 of D-fructose (the hemiacetal carbon) reacts with the —OH group on carbon 1 of D-glucose (the hemiacetal carbon). 6 CH

CH2OH O

2OH

5 4

O 1

OH

OH

OH 2

3

1

OH OH

OH

␣,  (1 2) linkage

OH

␣-Glucose 2OH

O

5

OH

CH2OH O

2

HO

HO 2

CH2OH 4

 H2O

O

6 CH

3

CH2OH

1

OH

OH

 -Fructose

Sucrose

Sucrose, unlike maltose, cellobiose, and lactose, is a nonreducing sugar. No hemiacetal is present in the molecule, because the glycosidic linkage involves the reducing ends of both monosaccharides. Sucrose, in the solid state and in solution, exists in only one form—there are no a and b isomers, and an open-chain form is not possible. Sucrase, the enzyme needed to break the a, b(1 —> 2) linkage in sucrose, is present in the human body. Hence sucrose is an easily digested substance. Sucrose hydrolysis (digestion) produces an equimolar mixture of glucose and fructose called invert sugar (see Figure 18.21). Figure 18.20 Space-filling model of the disaccharide sucrose.

D-Sucrose

 H2O

H or sucrase

D-glucose

 D-fructose

Invert sugar

18.14 General Characteristics of Polysaccharides

587

When sucrose is cooked with acid-containing foods such as fruits or berries, partial hydrolysis takes place, forming some invert sugar. Jams and jellies prepared in this manner are actually sweeter than the pure sucrose added to the original mixture because one-to-one mixtures of glucose and fructose taste sweeter than sucrose. The Chemical Connections feature on page 588 discusses the increasing trend of using high-fructose corn syrup (HFCS) instead of sucrose as a sweetener in beverages and processed foods. The topic of artificial sweeteners is considered in the Chemical Connections feature on page 590.

EXAMPLE 18.7 Distinguishing Common Disaccharides from Each Other on the Basis of Structural and Reaction Characteristics

Which of the disaccharides maltose, cellobiose, lactose, and sucrose has each of the following structural or reaction characteristics? There may be more than one correct answer for a given characteristic. a. b. c. d.

Both monosaccharide units present are glucose. It is a reducing sugar. It can exist in alpha and beta forms. Its glycoside linkage is an a(1 : 4) linkage.

Solution

a. Maltose and cellobiose. Both of these disaccharides contain two glucose units. They differ from each other in the type of glycosidic linkage present; maltose contains an a(1 : 4) linkage and cellobiose contains a b(1 : 4) glycosidic linkage. b. Maltose, cellobiose, and lactose. A reducing sugar has one “free” hemiacetal carbon atom. Such is the case any time two monosaccharides are bonded through a (1 : 4) glycosidic linkage. Sucrose is the only one of the four disaccharides that does not have a (1 : 4) glycosidic linkage; its glycosidic linkage is of the (1 : 2) variety. c. Maltose, cellobiose, and lactose. A “free” hemiacetal carbon atom is a prerequisite for alpha and beta cyclic forms. Sucrose is the only one of the four disaccharides for which this is not the case. Reducing sugars (part b) and alpha-beta forms are based on the same structural feature. d. Maltose. Maltose, cellobiose, and lactose all have (1 : 4) glycosidic linkages. However, only maltose has an a(1 : 4) linkage; the other two monosaccharides have b(1 : 4) linkages.

Practice Exercise 18.7 Which of the disaccharides maltose, cellobiose, lactose, and sucrose has each of the following structural or reaction characteristics? There may be more than one correct answer for a given characteristic. a. b. c. d.

Two different monosaccharide units are present. Hydrolysis produces only monosaccharides. Its glycosidic linkage is a “head-to-head” linkage. It is not a reducing sugar.

Answers: a. Lactose, sucrose; b. Maltose, cellobiose, lactose, sucrose; c. Sucrose; d. Sucrose

Figure 18.21 Honeybees and many other insects possess an enzyme called invertase that hydrolyzes sucrose to invert sugar. Thus honey is predominantly a mixture of D-glucose and D-fructose with some unhydrolyzed sucrose. Honey also contains flavoring agents obtained from the particular flowers whose nectars are collected. Whether a person eats monosaccharides individually, as in honey, or linked together, as in sucrose, they end up the same way in the human body: as glucose and fructose.

18. 8.114 GENERAL CHARACTERISTICS OF POLYSACCHARIDES A polysaccharide is a polymer that contains many monosaccharide units bonded to each other by glycosidic linkages. Polysaccharides are often also called glycans. Glycan is an alternate name for a polysaccharide. Important parameters that distinguish various polysaccharides (or glycans) from each other are: 1. The identity of the monosaccharide repeating unit(s) in the polymer chain. The more abundant polysaccharides in nature contain only one type of monosaccharide repeating unit. Such polysaccharides, including starch, glycogen, cellulose, and chitin, are examples of homopolysaccharides. A homopolysaccharide is a polysaccharide in

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Changing Sugar Patterns: Decreased Sucrose, Increased Fructose

For many decades, until the mid-1970s, the disaccharide sucrose (table sugar) was the main sweetener added to foods consumed by humans, particularly sweetened beverages. In the last 30 years, however, sucrose use has decreased steadily, with high-fructose corn syrup (HFCS) progressively displacing sucrose. The per capita consumption increase for fructose, a monosaccharide, is matched with an almost equal decline in sucrose use, as shown in the accompanying graph.

120 Total caloric sweeteners

Pounds per person

100

80

60 Refined sugar (sucrose) 40 High-fructose corn syrup 20

1970 1975 1980 1985 1990 1995 2000 2005 Per capita consumption in the United States, in pounds, of selected sweeteners (1970–2005).

Three major reasons for the switch from sucrose to highfructose corn syrup are

1. HFCS is cheaper to produce because of the relative abundance of corn, farm subsidies, and sugar import tariffs in the United States. 2. HFCS is easier to blend and transport because it is a liquid. 3. HFCS usage leads to products with a much longer shelf life. The HFCS production process, first introduced in 1957, involves milling corn to produce corn starch and then hydrolyzing the starch (a glucose polymer; Section 18.15) to glucose using the enzymes a-amylase and glucoamylase (Section 21.3). The glucose so produced is then treated with the enzyme glucose isomerase to produce a mixture of glucose and fructose. The isomerase enzymatic process produces HFCS whose composition is 42% fructose, 50% glucose, and 8% other sugars (HFCS-42). Concentration procedures are then used to produce a syrup that is 90% fructose (HFCS-90). HFCS-42 and HFCS-90 are then blended to produce HFCS-55, which is 55% fructose, 41% glucose, and 4% other sugars. HFCS-55 is the preferred sweetener used by the soft drink industry, although HFCS-42 is commonly used as a sweetener in many processed food products. HFCS-55 has properties, including sweetness, that are very similar to sucrose, which is 50% glucose and 50% fructose; remember that sucrose is a disaccharide in which the monosaccharides are glucose and fructose. Concentrated fruit juices, particularly apple juice, are also used to sweeten beverages. The first listed ingredient in most fruit juice blends is apple juice, which actually provides more fructose relative to glucose than either sucrose or HFCS-55. A one-cup serving of apple juice contains 4.22 g of sucrose, 6.20 g of glucose, and 13.89 g of fructose. Pear juice and grape juice also have very high fructose levels relative to glucose. Fruits are much better natural sources of fructose than are vegetables; only a few vegetables have higher fructose levels than glucose levels. The following two tables, one for fruits and one for vegetables, shows sucrose, glucose, and fructose amounts present per serving.

Sucrose, Glucose, and Fructose Amounts, per Serving, in Selected Fruits Food Item

Serving Size

apple avocado banana blueberries cantaloupe cherries grapes orange peach pear pineapple plum raspberries strawberries

1 medium 1 fruit 1 medium 1 cup 1/8 melon 1 cup 1 cup 1 medium 1 medium 1 medium 1 cup diced 1 medium 1 cup 1 cup

Sucrose (g)

Glucose (g)

Fructose (g)

2.86 0.10 2.82 0.16 3.00 0.18 0.24 5.99 4.66 1.29 8.48 1.04 0.25 0.20

3.35 0.14 5.88 7.08 1.06 7.71 11.52 2.76 1.91 4.58 2.70 3.35 2.29 3.39

8.14 0.14 5.72 7.21 1.29 6.28 13.01 3.15 1.50 10.34 3.18 2.03 2.89 4.15

18.14 General Characteristics of Polysaccharides

Food Item

Serving Size

watermelon broccoli carrots, baby corn, sweet cucumber onions peas, green potatoes spinach sweet potato tomatoes

1/16 melon 1 cup 10 small 1 ear 1 cup 1 slice 1 cup 1 medium 1 cup 1 medium 1 medium

In nutrition discussions, monosaccharides and disaccharides are called simple carbohydrates, and polysaccharides are called complex carbohydrates.

Sucrose (g) 3.46 0.09 2.70 1.85 0.00 0.44 7.24 0.36 0.02 3.28 0.00

Glucose (g) 4.52 0.43 1.00 0.45 0.75 0.74 0.17 0.70 0.03 1.25 1.54

589

Fructose (g) 9.61 0.60 1.00 0.43 0.89 0.44 0.57 0.58 0.04 0.91 1.69

which only one type of monosaccharide monomer is present. Polysaccharides whose structures contain two or more types of monosaccharide monomers, including hyaluronic acid and heparin, are called heteropolysaccharides. A heteropolysaccharide is a polysaccharide in which more than one (usually two) type of monosaccharide monomer is present. 2. The length of the polymer chain. Polysaccharide chain length can vary from less than a hundred monomer units to up to a million monomer units. 3. The type of glycosidic linkage between monomer units. As with disaccharides (Section 18.13), several different types of glycosidic linkages are encountered in polysaccharide structures. 4. The degree of branching of the polymer chain. The ability to form branched-chain structures distinguishes polysaccharides from the other two major types of biochemical polymers: proteins (Chapter 20) and nucleic acids (Chapter 22), which occur only as linear (unbranched) polymers. Figure 18.22 illustrates important general structural considerations relative to polysaccharides.

Figure 18.22 The polymer chain of a polysaccharide may be unbranched or branched. The monosaccharide monomers in the polymer chain may all be identical or two or more kinds of monomers may be present.

Chain continues

Monosaccharide unit

Branch point

Glycosidic linkage

Branch point

(a) Unbranched-chain homopolysaccharide

(b) Branched-chain homopolysaccharide

Chain continues

Branch point

Monosaccharide unit

Glycosidic linkage

(c) Unbranched-chain heteropolysaccharide

Branch point (d) Branched-chain heteropolysaccharide

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Artificial Sweeteners

Because of the high caloric value of sucrose, it is often difficult to satisfy a demanding “sweet tooth” with sucrose without adding pounds to the body frame or inches to the waistline. Artificial sweeteners, which provide virtually no calories, are now used extensively as a solution to the “sucrose problem.” Three artificial sweeteners that have been widely used are saccharin, sodium cyclamate, and aspartame. O J

O B NHO SO O Na B O

NOH S O

O

Saccharin

Sodium cyclamate

three-fourths of current artificial sweetener use. It tastes like sucrose but is 150 times sweeter. It provides 4 kcal/g, as does sucrose, but because so little is used, its calorie contribution is negligible. Aspartame has quickly found its way into almost every diet food on the market today. The safety of aspartame lies with its hydrolysis products: the amino acids aspartic acid and phenylalanine. These amino acids are identical to those obtained from digestion of proteins. The only danger aspartame poses is that it contains phenylalanine, an amino acid that can lead to mental retardation among young children suffering from PKU (phenylketonuria). Labels on all products containing aspartame warn phenylketonurics of this potential danger. Sucralose, a derivative of sucrose, is a new low-calorie entry into the artificial sweetener market. It is synthesized from sucrose by substitution of three chlorine atoms for hydroxyl groups. 6 CH2OH

COOH A A CH2 CH2 A A H2NO CH O C O NH O CH O C O O O CH3 B B O O

O

Cl 4

OH

Aspartame

6

ClCH2

All three of these artificial sweeteners have received much publicity because of concern about their safety. Saccharin is the oldest of the artificial sweeteners, having been in use for over 100 years. Questions about its safety arose in 1977 from a study that suggested that large doses of saccharin caused bladder tumors in rats. As a result, the FDA proposed banning saccharin, but public support for its use caused Congress to impose a moratorium on the ban. In 1991, on the basis of many further studies, the FDA withdrew its proposal to ban saccharin. Sodium cyclamate, approved by the FDA in 1949, dominated the artificial sweetener market for 20 years. In 1969, principally on the basis of one study suggesting that it caused cancer in laboratory animals, the FDA banned its use. Further studies have shown that neither sodium cyclamate nor its metabolites cause cancer in animals. Reapproval of sodium cyclamate has been suggested, but there has been little action by the FDA. Interestingly, Canada has approved sodium cyclamate use but banned the use of saccharin. Aspartame (Nutra-Sweet), approved by the FDA in 1981, is used in both the United States and Canada and accounts for

1

OH

O HO

O 2

CH2Cl 1

OH

An advantage of sucralose over aspartame is that it is heat-stable and can therefore be used in cooked food. Aspartame loses its sweetness when heated. Sucralose is 600 times sweeter than sucrose and has a similar taste. It is calorie-free because it cannot be hydrolyzed as it passes through the digestive tract. Name

Type

lactose glucose sucrose fructose sodium cyclamate aspartame saccharin sucralose

disaccharide monosaccharide disaccharide monosaccharide noncarbohydrate noncarbohydrate noncarbohydrate disaccharide derivative

Sweetness* 16 74 100 173 3,000 15,000 35,000 60,000

*Sweetness is compared to table sugar (sucrose), which is 100 on the scale.

Unlike monosaccharides and most disaccharides, polysaccharides are not sweet and do not test positive in Tollens and Benedict’s solutions. They have limited water solubility because of their size. However, the —OH groups present can individually become hydrated by water molecules. The result is usually a thick colloidal suspension of the

18.15 Storage Polysaccharides

591

polysaccharide in water. Polysaccharides, such as flour and cornstarch, are often used as thickening agents in sauces, desserts, and gravy. Although there are many naturally occurring polysaccharides of biochemical importance, we will focus on only six of them: starch, glycogen, cellulose, chitin, hyaluronic acid, and heparin. Starch and glycogen are examples of storage polysaccharides, cellulose and chitin are structural polysaccharides, and hyaluronic acid and heparin are acidic polysaccharides.

18. 8.115 STORAGE POLYSACCHARIDES A storage polysaccharide is a polysaccharide that is a storage form for monosaccharides and is used as an energy source in cells. In cells, monosaccharides are stored in the form of polysaccharides rather than as individual monosaccharides in order to lower the osmotic pressure within cells. Osmotic pressure depends on the number of individual molecules present (Section 8.9). Incorporating many monosaccharide molecules into a single polysaccharide molecule results in a dramatic reduction in molecular numbers. The most important storage polysaccharides are starch (in plant cells) and glycogen (in animal and human cells).

Starch

Amylose and cellulose are both linear chains of D-glucose molecules. They are stereoisomers that differ in the configuration at carbon 1 of each D-glucose unit. In amylose, a-D-glucose is present; in cellulose, b-D-glucose.

Starch is a homopolysaccharide containing only glucose monosaccharide units. It is the energy-storage polysaccharide in plants. If excess glucose enters a plant cell, it is converted to starch and stored for later use. When the cell cannot get enough glucose from outside the cell, it hydrolyzes starch to release glucose. Two different polyglucose polysaccharides can be isolated from most starches: amylose and amylopectin. Amylose, a straight-chain glucose polymer, usually accounts for 15%–20% of the starch; amylopectin, a branched glucose polymer, accounts for the remaining 80%–85% of the starch. In amylose’s non-branched structure, the glucose units are connected by (1: 4) glycosidic linkages. CH2OH O

The glucose polymers amylose, amylopectin, and glycogen compare as follows in molecular size and degree of branching. Amylose:

Up to 1000 glucose units; no branching Amylopectin: Up to 100,000 glucose units; branch points every 25–30 glucose units Glycogen: Up to 1,000,000 glucose units; branch points every 8–12 glucose units

G D O

CH2OH O G D O

OH

␣(1

OH

CH2OH O G D O

OH

␣(1

4)

G D O

OH

␣(1

4)

OH

CH2OH O

OH

G G O

OH 4)

OH

Starch (amylose)

The number of glucose units present in an amylose chain depends on the source of the starch; 300–500 monomer units are usually present. Amylopectin, the other polysaccharide in starch, has a high degree of branching in its polyglucose structure. A branch occurs about once every 25–30 glucose units. The branch points involve a(1 —> 6) linkages (Figure 18.23). Because of the branching, amylopectin has a larger average molecular mass than the linear amylose. Up to 100,000 glucose units may be present in an amylopectin polymer chain. All of the glycosidic linkages in starch (both amylose and amylopectin) are of the a type. In amylose, they are all (1 —> 4); in amylopectin, both (1 —> 4) and (1 —> 6) linkages are present. Because both types of a linkages can be broken through hydrolysis within the human digestive tract (with the help of enzymes), starch has nutritional value for humans. The starches present in potatoes and cereal grains (wheat, rice, corn, etc.) account for approximately two-thirds of the world’s food consumption. Iodine is often used to test for the presence of starch in solution. Starch-containing solutions turn a dark blue-black when iodine is added (see Figure 18.24). As starch is broken down through acid or enzymatic hydrolysis to glucose monomers, the blue-black color disappears.

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Chapter 18 Carbohydrates

CH2OH O OH

CH2OH O 1

4

O

␣(1

1

OH

4)

OH

OH

␣(1

6)

O 6

CH2OH O 4

OH

CH2

5 1

4

O

␣(1

CH2OH O

O 1

OH

4

O

␣(1

4)

OH

1

OH

4)

OH

OH

␣(1

6)

O CH2OH O 4 OH

6

CH2OH O 1

4 OH

O

␣(1

4)

OH

CH2

CH2OH O

O 1

4

O

␣(1

4)

OH

OH

1

O

␣(1

OH

4 OH

1

An ␣(1 6) linkage is present in the amylopectin structure at each branch point.

4)

OH

(a)

(b)

Figure 18.23 Two perspectives on the structure of the polysaccharide amylopectin. (a) Molecular structure of amylopectin. (b) An overview of the branching that occurs in the amylopectin structure. Each dot is a glucose unit.

The amount of stored glycogen in the human body is relatively small. Muscle tissue is approximately 1% glycogen, liver tissue 2%–3%. However, this amount is sufficient to take care of normal-activity glucose demands for about 15 hours. During strenuous exercise, glycogen supplies can be exhausted rapidly. At this point, the body begins to oxidize fat as a source of energy. Many marathon runners eat large quantities of starch foods the day before a race. This practice, called carbohydrate loading, maximizes body glycogen reserves.

Figure 18.24 Use of iodine to test for starch. Starch-containing solutions and foods turn dark blue-black when iodine is added.

Glycogen Glycogen, like starch, is a polysaccharide containing only glucose units. It is the glucose storage polysaccharide in humans and animals. Its function is thus similar to that of starch in plants, and it is sometimes referred to as animal starch. Liver cells and muscle cells are the storage sites for glycogen in humans. Glycogen has a structure similar to that of amylopectin; all glycosidic linkages are of the a type, and both (1 —> 4) and (1 —> 6) linkages are present. Glycogen and amylopectin differ in the number of glucose units between branches and in the total number of glucose units present in a molecule. Glycogen is about three times more highly branched than amylopectin, and it is much larger, with up to 1,000,000 glucose units present. When excess glucose is present in the blood (normally from eating too much starch), the liver and muscle tissue convert the excess glucose to glycogen, which is then stored in these tissues. Whenever the glucose blood level drops (from exercise, fasting, or normal activities), some stored glycogen is hydrolyzed back to glucose. These two opposing processes are called glycogenesis and glycogenolysis, the formation and decomposition of glycogen, respectively. Glucose

Glycogenesis Glycogenolysis

glycogen

Glycogen is an ideal storage form for glucose. The large size of these macromolecules prevents them from diffusing out of cells. Also, conversion of glucose to glycogen reduces

18.16 Structural Polysaccharides

593

Figure 18.25 The small, dense particles within this electron micrograph of a liver cell are glycogen granules.

osmotic pressure (Section 8.9). Cells would burst because of increased osmotic pressure if all of the glucose in glycogen were present in cells in free form. High concentrations of glycogen in a cell sometimes precipitate or crystallize into glycogen granules. These granules are discernible in photographs of cells under electron microscope magnification (Figure 18.25).

18. 8.116 STRUCTURAL POLYSACCHARIDES A structural polysaccharide is a polysaccharide that serves as a structural element in plant cell walls and animal exoskeletons. Two of the most important structural polysaccharides are cellulose and chitin. Both are homopolysaccharides.

Cellulose Cellulose, the structural component of plant cell walls, is the most abundant naturally occurring polysaccharide. The “woody” portions of plants—stems, stalks, and trunks— have particularly high concentrations of this fibrous, water-insoluble substance. Like amylose, cellulose is an unbranched glucose polymer. The structural difference between cellulose and amylose, which gives them completely different properties, is that the glucose residues present in cellulose have a beta-configuration whereas the glucose residues in amylose have an alpha-configuration. The glycosidic linkages in cellulose are therefore b(1 : 4) linkages rather than a(1 : 4) linkages.

CH2OH O ZD

OH

CH2OH O

4

D O D

OH

1

D O D  (1

CH2OH O

OH 4)

 (1

4)

CH2OH O D O D  (1

OH 4)

DZ O D

OH

OH

OH

OH

This difference in glycosidic linkage type causes cellulose and amylose to have different molecular shapes. Amylose molecules tend to have spiral-like structures whereas cellulose molecules tend to have linear structures. The linear (straight-chain) cellulose molecules, when aligned side by side, become water-insoluble fibers because of interchain hydrogen bonding involving the numerous hydroxyl groups present. Typically, cellulose chains contain about 5000 glucose units, which gives macromolecules with molecular masses of about 900,000 amu. Cotton is almost pure cellulose (95%), and wood is about 50% cellulose.

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Figure 18.26 A sandwich such as this is high in dietary fiber; that is, it is a cellulose-rich “meal.” The word chitin is pronounced “kye-ten”; it rhymes with Titan.

Even though it is a glucose polymer, cellulose is not a source of nutrition for human beings. Humans lack the enzymes capable of catalyzing the hydrolysis of b(1 —> 4) linkages in cellulose. Even grazing animals lack the enzymes necessary for cellulose digestion. However, the intestinal tracts of animals such as horses, cows, and sheep contain bacteria that produce cellulase, an enzyme that can hydrolyze cellulose b(1 —> 4) linkages and produce free glucose from cellulose. Thus grasses and other plant materials are a source of nutrition for grazing animals. The intestinal tracts of termites contain the same microorganisms, which enable termites to use wood as their source of food. Microorganisms in the soil can also metabolize cellulose, which makes possible the biodegradation of dead plants. Despite its nondigestibility, cellulose is still an important component of a balanced diet. It serves as dietary fiber. Dietary fiber provides the digestive tract with “bulk” that helps move food through the intestinal tract and facilitates the excretion of solid wastes. Cellulose readily absorbs water, leading to softer stools and frequent bowel action. Links have been found between the length of time stools spend in the colon and possible colon problems. High-fiber food may also play a role in weight control. Obesity is not seen in parts of the world where people eat large amounts of fiber-rich foods (see Figure 18.26). Many of the weight-loss products on the market are composed of bulk-inducing fibers such as methylcellulose. Some dietary fibers bind lipids such as cholesterol (Section 19.9) and carry them out of the body with the feces. This lowers blood lipid concentrations and, possibly, the risk of heart and artery disease. About 25–35 grams of dietary fiber daily is a desirable intake. This is two to three times higher than the average intake of Americans.

Chitin

Figure 18.27 Chitin, a linear b(1 —> 4) polysaccharide, produces the rigidity in the exoskeletons of crabs and other arthropods.

Chitin is a polysaccharide that is similar to cellulose in both function and structure. Its function is to give rigidity to the exoskeletons of crabs, lobsters, shrimp, insects, and other arthropods (see Figure 18.27). It also occurs in the cell walls of fungi. Structurally, chitin is a linear polymer (no branching) with all b(1 —> 4) glycosidic linkages, as is cellulose. Chitin differs from cellulose in that the monosaccharide present is an N-acetyl amino derivative of D-glucose (Section 18.12). Figure 18.28 contrasts the structures of chitin and cellulose.

Figure 18.28 The structures of cellulose (a) and chitin (b). In both substances, all glycosidic linkages are of the b(1 —> 4) type.

CH2OH O

CH2OH O O

OH

CH2OH O 4 1

O

OH β (1

4)

OH β (1

4)

OH

OH

OH (a)

CH2OH O

CH2OH O O

OH

4 1

O

OH β (1

4)

CH3 (b)

4)

NH C

NH

CH3

O

OH β (1

C

NH C

CH2OH O

O

CH3

O

18.17 Acidic Polysaccharides

595

Types of Glycosidic Linkages for Common Glucose-Containing Di- and Polysaccharides ␣(1

4) linkages

Maltose Glucose

Glucose

Amylose Unbranched glucose polymer (a form of starch)

␣(1 4) and ␣(1 6) linkages

␤(1

␣,␤(1

4) linkages

Amylopectin

Sucrose

Lactose

Branched glucose polymer (a form of starch)

Galactose

Glycogen

Glucose

2) linkages

Glucose

Glucose

Fructose

Cellobiose

Highly branched glucose polymer

Glucose

Cellulose Unbranched glucose polymer

The Chemistry at a Glance feature above summarizes the types of glycosidic linkages present in commonly encountered glucose-containing di- and polysaccharides.

18. 8.117 ACIDIC POLYSACCHARIDES An acidic polysaccharide is a polysaccharide with a disaccharide repeating unit in which one of the disaccharide components is an amino sugar and one or both disaccharide components has a negative charge due to a sulfate group or a carboxyl group. Unlike the polysaccharides discussed in the previous two sections, acidic polysaccharides are heteropolysaccharides; two different monosaccharides are present in an alternating pattern. Acidic polysaccharides are involved in a variety of cellular functions and tissues (Figure 18.29). Two of the most well-known acidic polysaccharides are hyaluronic acid and heparin, both of which have unbranched-chain structures.

Hyaluronic Acid The structure of hyaluronic acid contains alternating residues of N-acetyl-b-D-glucosamine and D-glucuronic acid. CH2OH O

HO

OH

OH

HO NH C

Figure 18.29 Acidic polysaccharides associated with the connective tissue of joints give hurdlers such as these the flexibility needed to accomplish their task.

COOH O

OH

OH OH

O

CH3 N-Acetyl- -D-glucosamine

D-Glucuronic

acid

Both of these monosaccharide derivatives have been encountered previously. N-acetyl-D-glucosamine is the repeating unit in chitin (see Section 18.16). Glucuronic acid is derived

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Chapter 18 Carbohydrates

from glucose by oxidation of the —OH group at carbon 6 to an acid group (see Section 18.12). A section of the polymeric structure for hyaluronic acid is COOH O O

CH2OH O

COOH O O

O HO

OH

(1

(1

3)

OH

O

O HO

OH 4)

(1

NH C

CH2OH O

3)

OH

NH C

O

CH3

O

CH3

In this structure, note the alternating pattern of glycosidic bond types, b(1 —> 3) and b(1 —> 4). There are approximately 50,000 disaccharide units per chain. Highly viscous hyaluronic acid solutions serve as lubricants in the fluid of joints and they are also associated with the jelly-like consistency of the vitreous humor of the eye. (The Greek word hyalos means “glass”; hyaluronic acid solutions have a glass-like appearance.)

Heparin The best known of heparin’s biochemical functions is that of an anticoagulant; it helps prevent blood clots. It binds strongly to a protein involved in terminating the process of blood clotting, thus inhibiting blood clotting. The monosaccharides present in the disaccharide repeating unit for heparin are D-glucuronate-2-sulfate and N-sulfo-D-glucosamine-6-sulfate, both of which contain two negatively charged acidic groups. COO⫺

CH2OSO3⫺ O

O

O

4

OH

1 2

␣(1

OSO3⫺ D-Glucuronate-

2-sulfate

O

4 4)

OH

1 2

O

NHSO3⫺ N-SulfoD-glucosamine-6-sulfate

Heparin is a small polysaccharide with only 15–90 disaccharide residues per chain.

18. 8.118 GLYCOLIPIDS AND GLYCOPROTEINS: CELL RECOGNITION

The prefix glyco-, used in the terms glycolipid and glycoprotein, is derived from the Greek word glykys, which means “sweet.” Most monosaccharides and disaccharides have a sweet taste.

Prior to 1960, the biochemistry of carbohydrates was thought to be rather simple. These compounds served (1) as energy sources for plants, humans, and animals and (2) as structural materials for plants and arthropods. Research since then has shown that oligosaccharides (Section 18.2) attached through glycosidic linkages to lipid molecules (Chapter 19) or to protein molecules (Chapter 20) have a wide variety of cellular functions including the process of cell recognition. Such molecules, called glycolipids and glycoproteins, respectively, often govern how individual cells of differing function within a biochemical system recognize each other and how cells interact with invading bacteria and viruses. A glycolipid is a lipid molecule that has one or more carbohydrate (or carbohydrate derivative) units covalently bonded to it. Similarly, a glycoprotein is a protein molecule that has one or more carbohydrate (or carbohydrate derivative) units covalently bonded to it. The lipid or protein part of the glycolipid or glycoprotein is incorporated into the cell membrane structure and the carbohydrate (oligosaccharide) part functions as a marker on the outer cell membrane surface. Cell recognition generally involves the interaction

18.19 Dietary Considerations and Carbohydrates

c

597

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onnections

“Good and Bad Carbs”: The Glycemic Index

The glycemic index (GI) is a dietary carbohydrate rating system that indicates how fast a particular carbohydrate is broken down into glucose (through hydrolysis) and the level of blood glucose that results. Its focal point is thus blood glucose levels. Slow generation of glucose, a modest rise in blood glucose, and a smooth return to normal blood glucose levels are desirable. A rapid increase (surge) in blood glucose levels, with a resulting overcorrection (from excess insulin production) that drops glucose levels below normal, is undesirable. Low-GI foods promote the first of these two effects, and high-Gl foods Low-Glycemic Foods (less than 55) low-fat yogurt, artificially sweetened grapefruit kidney beans low-fat yogurt, sugar sweetened apple, pear spaghetti orange low-fat ice cream* potato chips*

promote the latter. Selected examples of GI ratings for foods are given in the accompanying tables. Considerations relative to use of GI values such as these include the following: 1. At least one low-GI food should be part of each meal. 2. Fruits, vegetables, and legumes tend to have low-GI ratings. 3. Whole-grain foods, substances high in fiber, tend to have slower digestion rates. 4. High-GI rated foods should still be consumed, but as part of meals that also contain low-GI foods.

Intermediate-Glycemic Foods (55 to 70) 14 25 27 33 38 41 44 50 54

brown rice popcorn, sweet corn long-grain white rice mini shredded wheats cheese pizza Coca-Cola* raisins table sugar* white bread

55 55 56 58 60 63 64 65 70

High-Glycemic Foods (over 70) corn chips watermelon† Cheerios† french fries rice cakes pretzels cornflakes baked potato† dried dates†

72 72 74 76 82 83 84 85 103

*High in a lot of “empty calories,” so eat sparingly. Otherwise, they’ll crowd out more nutritious foods. †Don’t avoid these healthful foods. Instead, combine them with low-glycemic choices.

between the carbohydrate marker of one cell and a protein imbedded into the cell membrane of another cell. In the human reproductive process, fertilization involves a binding interaction between oligosaccharide markers on the outer membrane surface of an ovulated egg and protein receptor sites on a sperm cell membrane. This binding process is followed by release of enzymes by the sperm cell which dissolve the egg cell membrane allowing for entry of the sperm and the ensuing egg–sperm fertilization process. The oligosaccharide markers on cell surfaces that are the basis for blood types were considered in the Chemical Connections feature on page 580. Additional aspects of glycoprotein chemistry are considered in Section 20.17.

18. 8.119 DIETARY CONSIDERATIONS AND CARBOHYDRATES Foods high in carbohydrate content constitute over 50% of the diet of most people of the world—rice in Asia, corn in South America, cassava (a starchy root vegetable) in parts of Africa, the potato and wheat in North America, and so on. Current nutritional recommendations support such a situation; a balanced diet should ideally be about 60% carbohydrate. Nutritionists usually subdivide dietary carbohydrates into the categories simple and complex. A simple carbohydrate is a dietary monosaccharide or disaccharide. Simple carbohydrates are usually sweet to the taste and are commonly referred to as sugars (Section 18.8). A complex carbohydrate is a dietary polysaccharide. The main complex carbohydrates are starch and cellulose, substances not generally sweet to the taste.

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Chapter 18 Carbohydrates

Simple carbohydrates provide 20% of the energy in the U.S. diet. Half of this energy content comes from natural sugars and the other half from refined sugars added to foods. A natural sugar is a sugar naturally present in whole foods. Milk and fresh fruit are two important sources of natural sugars. A refined sugar is a sugar that has been separated from its plant source. Sugar beets and sugar cane are major sources for refined sugars. Despite claims to the contrary, refined sugars are chemically and structurally no different from the sugars naturally present in foods. The only difference is that the refined sugar is in a pure form, whereas natural sugars are part of mixtures of substances obtained from a plant source. Refined sugars are often said to provide empty calories because they provide energy but few other nutrients. Natural sugars, on the other hand, are accompanied by nutrients. A tablespoon of sucrose (table sugar) provides 50 calories of energy just as a small orange does. The small orange, however, also supplies vitamin C, potassium, calcium, and fiber; table sugar provides no other nutrients. The major dietary source for complex carbohydrates in the U.S. diet is grains, a source of both starch and fiber as well as of protein, vitamins, and minerals. The pulp of a potato provides starch, and the skin provides fiber. Vegetables such as broccoli and green beans are low in starch but high in fiber. A developing concern about dietary intake of carbohydrates involves how fast a given dietary carbohydrate is broken down to generate glucose within the human body. The term glycemic effect refers to how quickly carbohydrates are digested (broken down into glucose), how high blood glucose levels rise, and how quickly blood glucose levels return to normal. A measurement system called the glycemic index (GI) has been developed for rating foods in terms of their glycemic effect. The Chemical Connections feature on page 597 discusses this topic further.

c

O N C E P TS TO R E M E M B E R

Biochemistry. Biochemistry is the study of the chemical substances found in living systems and the chemical interactions of these substances with each other (Section 18.1). Carbohydrates. Carbohydrates are polyhydroxy aldehydes, polyhydroxy ketones, or compounds that yield such substances upon hydrolysis. Plants contain large quantities of carbohydrates produced via photosynthesis (Section 18.2). Carbohydrate classification. Carbohydrates are classified into three groups: monosaccharides, oligosaccharides, and polysaccharides (Section 18.3). Chirality and achirality. A chiral object is not identical to its mirror image. An achiral object is identical to its mirror image (Section 18.4). Chiral center. A chiral center is an atom in a molecule that has four different groups tetrahedrally bonded to it. Molecules that contain a single chiral center exist in a left-handed and a right-handed form (Section 18.4). Stereoisomerism. The atoms of stereoisomers are connected in the same way but are arranged differently in space. The major causes of stereoisomerism in molecules are structural rigidity and the presence of a chiral center (Section 18.5). Enantiomers and diastereomers. Two types of stereoisomers exist: enantiomers and diastereomers. Enantiomers have structures that are nonsuperimposable mirror images of each other. Enantiomers have identical achiral properties but different chiral properties. Diastereomers have structures that are not mirror images of each other (Section 18.5). Fischer projection formulas. Fischer projection formulas are twodimensional structural formulas used to depict the three-dimensional shapes of molecules with chiral centers (Section 18.6).

Chirality of monosaccharides. Monosaccharides are classified as D

or L stereoisomers on the basis of the configuration of the chiral center farthest from the carbonyl group (Section 18.6). Optical activity. Chiral compounds are optically active—that is, they rotate the plane of polarized light. Enantiomers rotate the plane of polarized light in opposite directions. The prefix () indicates that the compound rotates the plane of polarized light in a clockwise direction, whereas compounds that rotate the plane of polarized light in a counterclockwise direction have the prefix () (Section 18.7). Classification of monosaccharides. Monosaccharides are classified as aldoses or ketoses on the basis of the type of carbonyl group present. They are further classified as trioses, tetroses, pentoses, etc. on the basis of the number of carbon atoms present (Section 18.8). Important monosaccharides. Important monosaccharides include glucose, galactose, fructose, and ribose. Glucose and galactose are aldohexoses, fructose is a ketohexose, and ribose is an aldopentose (Section 18.9). Cyclic monosaccharides. Cyclic monosaccharides form through an intramolecular reaction between the carbonyl group and an alcohol group of an open-chain monosaccharide. These cyclic forms predominate in solution (Section 18.10). Reactions of monosaccharides. Five important reactions of monosaccharides are (1) oxidation to an acidic sugar, (2) reduction to a sugar alcohol, (3) glycoside formation, (4) phosphate ester formation, and (5) amino sugar formation (Section 18.12). Disaccharides. Disaccharides are glycosides formed from the linkage of two monosaccharides. The most important disaccharides are

Exercises and Problems

maltose, cellobiose, lactose, and sucrose. Each of these has at least one glucose unit in its structure (Section 18.13). Polysaccharides. Polysaccharides are polymers in which monosaccharides are the monomers. In homopolysaccharides only one type of monomer is present. Two or more monosaccharide monomers are present in heteropolysaccharides. Storage polysaccharides (starch, glycogen) are storage molecules for monosaccharides. Structural

k

599

polysaccharides (cellulose, chitin) serve as structural elements in plant cell walls and animal exoskeletons (Sections 18.14 to 18.17). Glycolipids and glycoproteins. Glycolipids and glycoproteins are molecules in which oligosaccharides are attached through glycosidic linkages to lipids and proteins, respectively. Such molecules often govern how cells of differing function interact with each other (Section 18.18).

EY R E A C T I O N S A N D E Q U AT I O N S

1. Monosaccharide oxidation (Section 18.12) Aldose or ketose ⫹ weak oxidizing agent S acidic sugar 2. Monosaccharide reduction (Section 18.12) Catalyst

Aldose or ketose ⫹ H2 888888n sugar alcohol 3. Glycoside (acetal) formation (Section 18.12) Cyclic monosaccharide ⫹ alcohol S glycoside (acetal) ⫹ H2O 4. Monosaccharide ester formation (Section 18.12) Monosaccharide ⫹ oxyacid S ester ⫹ H2O 5. Hydrolysis of disaccharide (Section 18.13) Catalyst

Disaccharide ⫹ H2O 888888n two monosaccharides

7. Hydrolysis of cellobiose (Section 18.13) D-Cellobiose

8. Hydrolysis of lactose (Section 18.13) D-Lactose

H⫹ or lactase

⫹ H2O 888888888n D-galactose ⫹ D-glucose

9. Hydrolysis of sucrose (Section 18.13) D-Sucrose

H⫹ or sucrase

⫹ H2O 888888888n D-fructose ⫹ D-glucose

10. Complete hydrolysis of starch (Section 18.15) H⫹ or enzymes

Starch ⫹ H2O 88888888888n many D-glucose 11. Complete hydrolysis of glycogen (Section 18.15) H⫹ or enzymes

Glycogen ⫹ H2O 88888888888n many D-glucose

6. Hydrolysis of maltose (Section 18.13) D-Maltose

H⫹ or cellobiase

⫹ H2O 88888888888n 2 D-glucose

H⫹ or maltase

⫹ H2O 888888888n 2 D-glucose

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Biochemical Substances (Section 18.1) 18.1 Define each of the following terms.

a. Biochemistry b. Biochemical substance 18.2 Contrast the relative amounts, by mass, of bioorganic and bioinorganic substances present in the human body. 18.3 What are the four major types of bioorganic substances? 18.4 For each of the following pairs of bioorganic substances, indicate

which member of the pair is more abundant in the human body. a. Proteins and nucleic acids b. Proteins and carbohydrates c. Lipids and carbohydrates d. Lipids and nucleic acids

Occurrence of Carbohydrates (Section 18.2) 18.5 Write a general chemical equation for photosynthesis. 18.6 What role does chlorophyll play in photosynthesis? 18.7 What are the two major functions of carbohydrates in the plant

kingdom? 18.8 What are the six major functions of carbohydrates in the human body? Structural Characteristics of Carbohydrates (Section 18.3) 18.9 Define the term carbohydrate.

18.10 What functional group is present in all carbohydrates? 18.11 Indicate how many monosaccharide units are present in each of

the following. a. Disaccharide b. Tetrasaccharide c. Oligosaccharide d. Polysaccharide 18.12 Identify, in general terms, the product produced from the complete hydrolysis of each of the following types of carbohydrates. a. Disaccharide b. Tetrasaccharide c. Oligosaccharide d. Polysaccharide Chirality (Section 18.4) 18.13 Explain what the term superimposable means. 18.14 Explain what the term nonsuperimposable means. 18.15 In each of the following lists of objects, identify those objects

that are chiral. a. Nail, hammer, screwdriver, drill bit b. Your hand, your foot, your ear, your nose c. The words TOT, TOOT, POP, PEEP 18.16 In each of the following lists of objects, identify those objects that are chiral. a. Baseball cap, glove, shoe, scarf b. Pliers, scissors, spoon, fork c. The words MOM, DAD, AHA, WAX

600

Chapter 18 Carbohydrates

18.17 Indicate whether the circled carbon atom in each of the following

molecules is a chiral center.

a. CH3 OC H2 OOH c. CH3 O C H O OH A Cl

d. CH3 O CH2 O C H O OH A CH3

molecules is a chiral center. a. CH3 OC H2 O NH2 b. CH3 O C H O CH3 A NH2

d. CH3 O C H O NH2 A Cl

18.19 Use asterisks to show the chiral center(s), if any, in the following

structures. a. H Cl A A ClO C O C O Br A A H Cl c.

b.

H Cl H A A A Br O C O COC O Cl A A A H Br Br

CH3

18.23 Classify each of the molecules in Problem 18.19 as chiral or

achiral. 18.24 Classify each of the molecules in Problem 18.20 as chiral or achiral. Stereoisomerism: Enantiomers and Diastereomers (Section 18.5) 18.25 What is the difference between constitutional isomers and stereoisomers? 18.26 Both enantiomers and diastereomers are stereoisomers. How do they differ? 18.27 What are two major structural features that can generate

stereoisomerism? 18.28 Explain why cis–trans isomers are diastereomers rather than enantiomers. Fischer Projection Formulas (Section 18.6)

)C Br Cl CH3 c.

18.20 Use asterisks to show the chiral center(s), if any, in the following

b.

CH3

molecules. H a.

d. CH2O CH OCH O CH OCH OCH2 A A A A A A OH OH OH OH OH OH

c.

H H H A A A Cl O C O COC O Cl A A A Br OH Br

O B CH3O CH OCH O CH OC O H A A A OH OH OH

OH c.

b. Cl

Cl

Cl OH

d.

OH

18.22 How many chiral centers are present in each of the following

molecular structures? Cl a. Br

b.

OH CH3

CH3

)C Br Cl H d. CH3

)C CH3 H CH3

)CCH3 Cl H CH3 d.

)C Cl HO H

18.21 How many chiral centers are present in each of the following

c.

CH3

b.

)C )C Br H Br H Cl Cl 18.30 Draw the Fischer projection formula for each of the following molecules. Cl a. b. OH

d. CH2O CH OCH O CH O CH2 A A A A A OH OH OH OH OH molecular structures? a. Cl

Cl

18.29 Draw the Fischer projection formula for each of the following

O B CH2O CH OCH O CH OC O H A A A A OH OH OH OH

structures. a. Br Cl A A ClO C O C O Cl A A Br Br

d.

b. CH3 O C H O OH A CH3

18.18 Indicate whether the circled carbon atom in each of the following

c. CH3 O C H O NH2 A CH3

c.

H

)C OH Cl

18.31 Draw a Fischer projection formula for the enantiomer of each

of the following monosaccharides. a. b. CHO A HO A H A H A OH H A H A OH HO CH2OH H c.

CHO A H A OH A H A OH A H A OH A HO A H CH2OH

d.

CH2OH A C PO A A OH A A H A A OH CH2OH

CHO A H A OH A HO A H A H A OH A HO A H CH2OH

Exercises and Problems 18.32 Draw a Fischer projection formula for the enantiomer of each

of the following monosaccharides. a. CHO b. A HO A H A HO A H HO A HO A H HO CH2OH c. HO HO H H

CHO A A H A A H A A OH A A OH CH2OH

d.

CHO CHO A A H A OH H A OH A and HO A H H A OH A CH2OH CH2OH CHO CHO c. A A H A OH HO A H A A HO A H H A OH and A A H A OH H A OH A A H A OH HO A H CH2OH CH2OH d. CH2OH CH2OH A A CPO CPO and A A H A OH H A H A A H A OH H A OH CH2OH CH2OH b.

CH2OH A C PO A A H A A H CH2OH

CH2OH A C PO A H A OH A H A OH A HO A H CH2OH

18.33 Classify each of the molecules in Problem 18.31 as a D enanti-

omer or an L enantiomer.

18.34 Classify each of the molecules in Problem 18.32 as a D enanti-

omer or an L enantiomer.

18.35 Characterize the members of each of the following pairs of

structures as (1) enantiomers, (2) diastereomers, or (3) neither enantiomers nor disastereomers. a. CHO CHO A A H A OH H A OH A and H A OH HO A H A A A H A OH H A OH CH2OH CH2OH b.

CHO A A OH A HO A H CH2OH H

c.

d.

CHO A H A OH A HO A H A H A OH A HO A H CH2OH CH2OH A C PO A HO A H A HO A H CH2OH

and

and

and

CHO A H A H A HO A H CH2OH CHO A HO A H A H A OH A HO A H A H A OH CH2OH CH2OH A C PO A HO A H A H A OH CH2OH

18.36 Characterize the members of each of the following pairs of

structures as (1) enantiomers, (2) diastereomers, or (3) neither enantiomers nor disastereomers. CHO CHO a. A A H A OH HO A H A and HO A H H A OH A A A HO A H H A OH CH2OH CH2OH

601

Properties of Enantiomers (Section 18.7) D-glucose and L-glucose would be expected to show differences in which of the following properties? a. Solubility in an achiral solvent b. Density c. Melting point d. Effect on plane-polarized light 18.38 D-glucose and L-glucose would be expected to show differences in which of the following properties? a. Solubility in a chiral solvent b. Freezing point c. Reaction with ethanol d. Reaction with ()-lactic acid 18.37

18.39 Compare ()-lactic acid and ()-lactic acid with respect to

each of the following properties. a. Boiling point b. Optical activity c. Solubility in water d. Reaction with ()-2,3-butanediol 18.40 Compare ()-glyceraldehyde and ()-glyceraldehyde with respect to each of the following properties. a. Freezing point b. Rotation of plane-polarized light c. Reaction with ethanol d. Reaction with ()-2,3-butanediol Classification of Monosaccharides (Section 18.8) 18.41 Classify each of the following monosaccharides as an aldose or a ketose. a. b. CH2OH CHO A A H O C O OH CP O A A H O C O OH HO O C O H A A H O C O OH HO O C O H A A H O C O OH H O CO OH A A CH2OH CH2OH c. CH2OH A CP O A CH2OH

d.

CH2OH A CP O A HO O C O H A CH2OH

602

Chapter 18 Carbohydrates

18.42 Classify each of the following monosaccharides as an aldose or

a ketose. CHO a. A HO O C O H A HO O C O H A HO O C O H A H O C O OH A CH2OH c.

CHO A HO O C O H A H O C O OH A CH2OH

b.

d.

CH2OH A CP O A HO O C O H A HO O C O H A CH2OH CH2OH A CP O A HO O C O H A HO O C O H A H O C O OH A CH2OH

18.43 Classify each monosaccharide in Problem 18.41 by its number

of carbon atoms and its type of carbonyl group.

18.44 Classify each monosaccharide in Problem 18.42 by its number

of carbon atoms and its type of carbonyl group.

18.45 Using the information in Figures 18.13 and 18.14, assign a

name to each of the monosaccharides in Problem 18.41.

18.46 Using the information in Figures 18.13 and 18.14, assign a

name to each of the monosaccharides in Problem 18.42.

Biochemically Important Monosaccharides (Section 18.9) 18.47 Indicate at what carbon atom(s) the structures of each of the following pairs of monosaccharides differ. a. D-Glucose and D-galactose b. D-Glucose and D-fructose c. D-Glyceraldehyde and dihydroxyacetone d. D-Ribose and 2-deoxy-D-ribose 18.48 Indicate whether the members of each of the following pairs of monosaccharides have the same molecular formula. a. D-Glucose and D-galactose b. D-Glucose and D-fructose c. D-Glyceraldehyde and dihydroxyacetone d. D-Ribose and 2-deoxy-D-ribose 18.49 Indicate which of the terms aldoses, ketoses, hexoses, and aldohexo-

ses apply to both members of each of the following pairs of monosaccharides. More than one term may apply in a given situation. a. D-Glucose and D-galactose b. D-Glucose and D-fructose c. D-Galactose and D-fructose d. D-Glyceraldehyde and D-ribose 18.50 Indicate which of the terms aldoses, ketoses, trioses, and aldohexoses apply to both members of each of the following pairs of monosaccharides. More than one term may apply in a given situation. a. D-Glucose and D-ribose b. D-Fructose and dihydroxyacetone c. D-Glyceraldehyde and dihydroxyacetone d. D-Galactose and D-ribose

18.52 Draw the Fischer projection formula for each of the following

monosaccharides. a. D-Galactose b. D-Ribose c. Dihydroxyacetone d. L-Glucose

18.53 To which of the common monosaccharides does each of the

following terms apply? a. Levulose b. Grape sugar c. Brain sugar 18.54 To which of the common monosaccharides does each of the following terms apply? a. Dextrose b. Fruit sugar c. Blood sugar Cyclic Forms of Monosaccharides (Section 18.10) 18.55 The intermolecular reaction that produces the cyclic forms of monosaccharides involves functional groups on which two carbon atoms in the case of each of the following? a. D-Glucose b. D-Galactose c. D-Fructose d. D-Ribose 18.56 How many carbon atoms and how many oxygen atoms are present in the ring portion of the cyclic forms of each of the following monosaccharides? a. D-Glucose b. D-Galactose c. D-Fructose d. D-Ribose 18.57 What is the structural difference between the alpha and beta

forms of D-glucose?

18.58 What is the structural difference between the alpha forms of D-glucose

carbon atoms. Why do both of these monosaccharides have cyclic forms that involve a five-membered ring? 18.60 Fructose and glucose both contain six carbon atoms. Why do the cyclic forms of fructose have a five-membered ring instead of the six-membered ring found in the cyclic forms of glucose? 18.61 The structure of glucose is sometimes written in an open-chain

form and sometimes as a cyclic hemiacetal structure. Explain why either form is acceptable. 18.62 When pure -D-glucose is dissolved in water, -D-glucose and -D-glucose are both soon present. Explain how this is possible. Haworth Projection Formulas (Section 18.11) 18.63 Identify each of the following structures as an -D-monosac-

charide or a -D-monosaccharide. CH2OH b. a. O

HO

OH

OH

OH CH2OH O

c.

18.51 Draw the Fischer projection formula for each of the following

monosaccharides. b. D-Glyceraldehyde a. D-Glucose d. L-Galactose c. D-Fructose

and D-galactose?

18.59 Fructose contains six carbon atoms, and ribose has only five

HO

OH

OH OH

d. HOCH2 OH

OH

HO

CH2OH O

O

CH2OH

OH OH

OH OH

Exercises and Problems 18.64 Identify each of the following structures as an -D-monosac-

charide or a -D-monosaccharide. CH2OH b. a. O HO OH HO

OH

18.79 Indicate whether each of the following structures is that of a

glycoside. CH2OH O

a.

OH

OH CH2OH O

c.

CH2OH O

OH OH d. HOCH2 O CH2OH

OOCH3

O

HO

OH

OH

OH

18.67 Draw the open-chain form for each of the monosaccharides in

Problem 18.63.

HO

OH

glycoside. CH2OH a. O

CH2OH O

18.71 Draw the Haworth projection formula for each of the following

18.75 In terms of oxidation and reduction, explain what occurs to

both D-glucose and Tollens solution when they react with each other. 18.76 Describe the chemical reaction used to detect glucose in urine that involves Benedict’s solution. 18.77 Draw structures for the following compounds.

a. Galactonic acid b. Galactaric acid c. Galacturonic acid d. Galactitol 18.78 Draw structures for the following compounds. a. Mannonic acid b. Mannaric acid c. Mannuronic acid d. Mannitol

OH

OH b.

CH2OH OOCH2OCH3

HO

name to each of the monosaccharides in Problem 18.63.

Reactions of Monosaccharides (Section 18.12) 18.73 Which of the following monosaccharides is a reducing sugar? b. D-Galactose a. D-Glucose d. D-Ribose c. D-Fructose 18.74 Which of the following monosaccharides will give a positive test with Benedict’s solution? b. D-Galactose a. D-Glucose d. D-Ribose c. D-Fructose

OH

18.80 Indicate whether each of the following structures is that of a

18.69 Using the information in Figures 18.13 and 18.14, assign a

monosaccharides. a. -D-Galactose b. -D-Galactose c. -L-Galactose d. -L-Galactose 18.72 Draw the Haworth projection formula for each of the following monosaccharides. a. -D-Mannose b. -D-Mannose c. -L-Mannose d. -L-Mannose

OOCH3

OH

Problem 18.64.

name to each of the monosaccharides in Problem 18.64.

CH2OH O

OOCH2OCH3

18.68 Draw the open-chain form for each of the monosaccharides in

18.70 Using the information in Figures 18.13 and 18.14, assign a

d.

OH

18.65 Identify whether each of the structures in Problem 18.63 is that

of a hemiacetal. 18.66 Identify whether each of the structures in Problem 18.64 is that of a hemiacetal.

OH CH2OH

OH

OOCH2OCH3

OH

HO

OH

OH c. HOCH2

CH2OH O

b.

HO

OH OH

603

OOCH3 CH2OH

HO OH

OH c. HOCH 2

O

CH2OH OOCH2OCH3

OH d.

HO

OH

O CH2OH OH

OOCH3

OH 18.81 For each structure in Problem 18.79, identify the configuration

at the acetal carbon atom as  or .

18.82 For each structure in Problem 18.80, identify the configuration

at the acetal carbon atom as  or .

18.83 Identify the alcohol needed to produce each of the compounds

in Problem 18.79 by reaction of the alcohol with the appropriate monosaccharide. 18.84 Identify the alcohol needed to produce each of the compounds in Problem 18.80 by reaction of the alcohol with the appropriate monosaccharide. 18.85 What is the difference in meaning between the terms glycoside

and glucoside?

18.86 What is the difference in meaning between the terms glycoside

and galactoside?

604

Chapter 18 Carbohydrates

18.87 Draw structures for the following compounds.

c.

a. Ethyl--D-glucoside b. Methyl--D-galactoside 18.88 Draw structures for the following compounds. a. Ethyl--D-galactoside b. Methyl--D-glucoside 18.89 Draw structures for the following compounds.

a. -D-Galactose 6-phosphate b. N-Acetyl--D-galactosamine 18.90 Draw structures for the following compounds. a. -D-Mannose 6-phosphate b. N-Acetyl--D-mannosamine

CH2OH O

CH2OH O

HO

G D O

OH

OH

OH CH2OH O

d.

OH CH2OH O OH

HO

G D O

OH

OH

OH Disaccharides (Section 18.13) 18.91 What monosaccharides are produced from the hydrolysis of the following disaccharides? a. Sucrose b. Maltose c. Lactose d. Cellobiose 18.92 What type of glycosidic linkage [a11 S 42, etc.] is present in each of the following disaccharides? a. Sucrose b. Maltose c. Lactose d. Cellobiose

OH

OH

18.98 What type of glycosidic linkage [a11 S 42, etc.] is present in

each of the following disaccharides? CH2OH a. O CH2OH OH O D OH O OH D OH OH OH CH2OH O

b.

18.93 Explain why lactose is a reducing sugar. 18.94 Explain why sucrose is not a reducing sugar.

HO

18.95 Indicate whether each of the following disaccharides gives a

positive or a negative Benedict’s test. a. Sucrose b. Maltose c. Lactose d. Cellobiose 18.96 Indicate whether each of the following disaccharides gives a positive or a negative Tollens test. a. Maltose b. Lactose c. Cellobiose d. Sucrose

HOCH2

OH CH2OH OH CH2OH O

c.

HO HO

G O G CH2

OH OH

OH

OH OH

b. CH2OH OH O OH

CH2OH O D O D

OH OH

OH

CH2

OH

HO

HO

OH

OH

OH CH2OH O G D O

OH

O

O

OH CH2OH O

d. O

HO

O

O

D D

each of the following disaccharides? a. CH2OH O

HO

D D

18.97 What type of glycosidic linkage [a11 S 42, etc.] is present in

OH

OH

OH

OH OH

18.99 For each of the structures in Problem 18.97, specify whether

OH

the disaccharide is in an  configuration or a  configuration, or neither. 18.100 For each of the structures in Problem 18.98, specify whether the disaccharide is in an  configuration or a  configuration, or neither. 18.101 Identify each of the structures in Problem 18.97 as a reducing

sugar or a nonreducing sugar.

Exercises and Problems 18.102 Identify each of the structures in Problem 18.98 as a reducing

sugar or a nonreducing sugar.

18.103 Using the information in Figures 18.13 and 18.14, assign a

name to each monosaccharide present in each of the structures in Problem 18.97. 18.104 Using the information in Figures 18.13 and 18.14, assign a name to each monosaccharide present in each of the structures in Problem 18.98. General Characteristics of Polysaccharides (Section 18.14) 18.105 What is the difference, if any, between a polysaccharide and a glycan? 18.106 What is the difference, if any, between a homopolysaccharide and a heteropolysaccharide? 18.107 What is the range for the polymer chain length in a

polysaccharide?

18.108 Contrast polysaccharides with mono- and disaccharides in

terms of general property differences.

Storage Polysaccharides (Section 18.15) 18.109 Indicate whether or not each of the following is a correct

characterization for the amylose form of starch. a. It is a homopolysaccharide. b. It contains two different types of monosaccharide molecules. c. It is a branched-chain glucose polymer. d. All glycosidic linkages present are a11 S 42. 18.110 Indicate whether or not each of the following is a correct characterization for glycogen. a. It is a homopolysaccharide. b. It contains two different types of monosaccharide molecules. c. It is a branched-chain glucose polymer. d. All glycosidic linkages present are a11 S 42. 18.111 What is the difference, if any, between the amylose and

amylopectin forms of starch in terms of the following? a. Relative abundance b. Length of polymer chain c. Type of glycosidic linkages present d. Type of monosaccharide monomers present 18.112 Which of the characterizations homopolysaccharide, heteropolysaccharide, straight-chain polysaccharide, and storage polysaccharide applies to both members of each of the following pairs of substances? More than one characterization may apply in a given situation. a. Glycogen and starch b. Amylose and amylopectin c. Glycogen and amylose d. Starch and amylopectin Structural Polysaccharides (Section 18.16) 18.113 Indicate whether or not each of the following is a correct char-

acterization for cellulose. a. It is an unbranched glucose polymer. b. Its glycosidic linkages are of the same type as those in starch. c. It is a source of nutrition for humans. d. One of its biochemical functions is that of dietary fiber.

605

18.114 Indicate whether or not each of the following is a correct char-

acterization for chitin. a. It is an unbranched polymer. b. Two different types of monomers are present. c. Glycosidic linkages present are the same as those in cellulose. d. The monomers present are glucose derivatives rather than glucose itself.

18.115 Indicate whether or not each of the following characteriza-

tions applies to (1) both cellulose and chitin, (2) to cellulose only, (3) to chitin only, or (4) to neither cellulose nor chitin. a. Storage polysaccharide b. Monomers are glucose units c. Glycosidic linkages are all a(1 : 4) d. An unbranched polymer 18.116 Indicate whether or not each of the following characterizations applies to (1) both cellulose and chitin, (2) to cellulose only, (3) to chitin only, or (4) to neither cellulose nor chitin. a. Structural polysaccharide b. Monomers are glucose derivatives c. Glycosidic linkages are all (1 : 4) d. Homopolysaccharide Acidic Polysaccharides (Section 18.17) 18.117 Indicate whether or not each of the following is a correct characterization for hyaluronic acid. a. Heteropolysaccharide b. Monomer repeating units are a disaccharide c. Two types of glycosidic linkages are present d. A very small polysaccharide 18.118 Indicate whether or not each of the following is a correct characterization for heparin. a. Heteropolysaccharide b. Monomer repeating units are a disaccharide c. Two types of glycosidic linkages are present d. A very small polysaccharide 18.119 What is the biological function for heparin? 18.120 What is the biological function for hyaluronic acid?

Glycolipids and Glycoproteins (Section 18.18) 18.121 In terms of structure, what is a glycolipid? 18.122 In terms of structure, what is a glycoprotein? 18.123 Describe the general features of the cell recognition process in

which glycoproteins participate. 18.124 Describe the general features of the cell recognition process in which glycolipids participate. Dietary Considerations and Carbohydrates (Section 18.19) 18.125 In a dietary context, what is the difference between a simple carbohydrate and a complex carbohydrate? 18.126 In a dietary context, what is the difference between a natural sugar and a refined sugar? 18.127 In a dietary context, what are empty calories? 18.128 In a dietary context, what is the glycemic effect?

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Chapter 18 Carbohydrates

A DD D IT IO NAL P R O BL L EM S 18.129 Indicate whether each of the following compounds is chiral or

achiral. a. 1-Chloro-2-methylpentane b. 2-Chloro-2-methylpentane c. 2-Chloro-3-methylpentane d. 3-Chloro-2-methylpentane 18.130 Indicate whether each of the following compounds is optically active or optically inactive. H a. b. H Cl

Cl

Cl

b.

CH2OH O HO

CH2OH O HO ?

OH

OH OH

O

c.

CH3

OH

OH CH2OH O

CH2OH O

Cl

CH2

?

Cl

c.

H

H

F

OH

O

HO

CH3

d.

COOH

OH

OH OH CH2OH O

OH

Cl H

COOH

OH

18.131 In which of the following pairs of monosaccharides do both

O

O

O

O

CH2 O CH O CH OC O CH2

OH

OH

OH

OH

18.133 What is the alkane of lowest molecular mass that is a chiral

compound?

18.134 What monosaccharide(s) is (are) obtained from the hydrolysis

H O C O OH H OC O OH CH2OH

?

O O O

O O O

of each of the following? a. Sucrose b. Glycogen c. Starch d. Amylose 18.135 Classify each of the following carbohydrates as a glucose polymer or a glucose-derivative polymer. a. Chitin b. Amylopectin c. Hyaluronic acid d. Glycogen 18.136 List the reactant(s) necessary to effect the following chemical changes. a. CHO COOH H O C O OH

OH OH

d.

CHO

H O C O OH H OC O OH

HO

OH OH OH

CHO

?

O O O

O



OH HO

O O O

members of the pair contain the same number of carbon atoms? a. Glyceraldehyde and glucose b. Dihydroxyacetone and ribose c. Ribose and deoxyribose d. Glyceraldehyde and dihydroxyacetone 18.132 Draw Fischer projection formulas for the four stereoisomers of the molecule

CH2OH O

H O C O OH H OC O OH

COOH CH2OH 18.137 Which of the characterizations homopolysaccharides, heteropolysaccharides, branched polysaccharides, and unbranched polysaccharides applies to both members of each of the following pairs of substances? More than one characterization may apply in a given case. a. Glycogen and cellulose b. Glycogen and amylopectin c. Amylose and chitin d. Heparin and hyaluronic acid 18.138 Match each of the following structural characteristics to the polysaccharides amylopectin, amylose, glycogen, cellulose, and chitin. A specific characteristic may apply to more than one of the polysaccharides. a. Contains both (1 : 4) and (1 : 6) glycosidic linkages b. Polymer chain is unbranched c. Glucose derivatives are present in the polymer chain d. Contains only (1 : 4) glycosidic linkages

H OC O OH COOH

multiple-Choice Practice Test 18.139 Which of the following statements relating to chirality is

incorrect? a. A chiral center is an atom in a molecule that has four different groups tetrahedrally bonded to it. b. A chiral molecule is a molecule whose mirror images are superimposable. c. Naturally occurring monosaccharides are almost always “right-handed.” d. The simplest example of a chiral monosaccharide is glyceraldehyde.

18.140 Which of the following statements concerning the D and L

forms of a monosaccharide is incorrect? a. Structurally they are nonsuperimposable mirror images of each other. b. They must contain the same number of chiral centers. c. They are enantiomers. d. They are diastereomers.

Multiple-Choice Practice Test

18.141 Which of the following is a correct characterization for the

monosaccharide glucose? a. Aldopentose b. Aldohexose c. Ketopentose d. Ketohexose 18.142 The structures of D-glucose and D-fructose differ at which carbon atom(s)? a. Carbon 1 only b. Carbon 2 only c. Carbon 1 and carbon 2 d. Carbon 1 and carbon 6 18.143 How many different forms of a D-monosaccharide are present, at equilibrium, in an aqueous solution of the monosaccharide? a. One b. Two c. Three d. Four 18.144 Which of the following disaccharides produces both D-glucose and D-fructose upon hydrolysis? a. Sucrose b. Lactose c. Maltose d. Cellobiose

18.145 In which of the following pairs of disaccharides do both

607

members of the pair have the same type of glycosidic linkage? a. Sucrose and lactose b. Cellobiose and maltose c. Lactose and cellobiose d. Sucrose and maltose 18.146 In which of the following pairs of carbohydrates are both members of the pair heteropolysaccharides? a. Cellulose and amylose b. Starch and chitin c. Hyaluronic acid and heparin d. Glycogen and amylopectin 18.147 In which of the following pairs of polysaccharides are both members of the pair structural polysaccharides? a. Glycogen and cellulose b. Starch and chitin c. Glycogen and starch d. Cellulose and chitin 18.148 The carbohydrate portion of glycolipids and glycoproteins that are involved in cell recognition processes is which of the following? a. Monosaccharide b. Glucose molecule c. Oligosaccharide d. Polysaccharide

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19

Lipids Chapter Outline 19.1 Structure and Classification of Lipids 608 19.2 Types of Fatty Acids 609 19.3 Physical Properties of Fatty Acids 613 19.4 Energy-Storage Lipids: Triacylglycerols 614 19.5 Dietary Considerations and Triacylglycerols 618 19.6 Chemical Reactions of Triacylglycerols 621

CHEMISTRY AT A GLANCE: Classification Schemes for Fatty Acid Residues Present in Triacylglycerols 628 19.7 Membrane Lipids: Phospholipids 628 19.8 Membrane Lipids: Sphingoglycolipids 634

CHEMISTRY AT A GLANCE: Terminology for and Structural Relationships Among Various Types of Fatty-Acid-Containing Lipids 634 19.9 Membrane Lipids: Cholesterol 635 19.10 Cell Membranes 637 19.11 Emulsification Lipids: Bile Acids 640 19.12 Messenger Lipids: Steroid Hormones 641 19.13 Messenger Lipids: Eicosanoids 644 19.14 Protective-Coating Lipids: Biological Waxes 646

CHEMISTRY AT A GLANCE: Types of Lipids in Terms of How They Function 648

Fats and oils are the most widely occurring types of lipids. Thick layers of fat help insulate polar bears against the effects of low temperatures.

T

here are four major classes of bioorganic substances: carbohydrates, lipids, proteins, and nucleic acids (Section 18.1). In the previous chapter we considered the first of these classes, carbohydrates. We now turn our attention to the second of the bioorganic classes, the compounds we call lipids. Lipids known as fats provide a major way of storing chemical energy and carbon atoms in the body. Fats also surround and insulate vital body organs, providing protection from mechanical shock and preventing excessive loss of heat energy. Phospholipids, glycolipids, and cholesterol (a lipid) are the basic components of cell membranes. Several cholesterol derivatives function as chemical messengers (hormones) within the body.

19.1 STRUCTURE AND CLASSIFICATION OF LIPIDS

CHEMICAL CONNECTIONS The Fat Content of Tree Nuts and Peanuts 620 Artificial Fat Substitutes 624 The Cleansing Action of Soap 625 Trans Fatty Acids and Blood Cholesterol Levels 626 Steroid Drugs in Sports 644 The Mode of Action for Anti-Inflammatory Drugs 646

Unlike carbohydrates and most other classes of compounds, lipids do not have a common structural feature that serves as the basis for defining such compounds. Instead, their characterization is based on solubility characteristics. A lipid is an organic compound found in living organisms that is insoluble (or only sparingly soluble) in water but soluble in nonpolar organic solvents. When a biochemical material (human, animal, or plant tissue) is homogenized in a blender and mixed with a nonpolar organic solvent, the substances that dissolve in the solvent are the lipids. Figure 19.1 shows the structural diversity that is associated with lipid molecules. Some are esters, some are amides, and some are alcohols; some are acyclic, some are cyclic, and some are polycyclic. The common thread that ties all of the compounds of Figure 19.1 together is solubility rather than structure. All are insoluble in water.

608 Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

609

19.2 Types of Fatty Acids

Figure 19.1 The structural formulas of these types of lipids illustrate the great structural diversity among lipids. The defining parameter for lipids is solubility rather than structure.

CH3 CH

CH3 CH2

CH

CH2

(CH2)29

O

O

O

O

C

O

C

O

C

O

C

(CH2)16 (CH2)14 (CH2)12 CH3

CH3

A fat

(CH2)3 CH

O

H3C

CH3

HO

+

+

N(CH3)3

N(CH3)3

CH2

CH2

CH2

CH2

O O P

CH

O

O

C

O

C

CH2

O P O

CH CH

(CH2)12 CH3

CH3

A glycerophospholipid

OH

O

CH

CH2

CH OH NH O

(CH2)14 (CH2)16 CH3

CH2OH O HO

O –

O

O CH2

A steroid

A biological wax

–

CH3

H3C

(CH2)14

CH3

CH3

C

O

OH CH CH

CH

CH2

CH OH NH O

(CH2)12

(CH2)12 CH3

CH3

A sphingophospholipid

C

O

(CH2)16 CH3

A sphingoglycolipid

For purposes of study, we will divide lipids into five categories on the basis of lipid function: 1. 2. 3. 4. 5.

Energy-storage lipids (triacylglycerols) Membrane lipids (phospholipids, sphingoglycolipids, and cholesterol) Emulsification lipids (bile acids) Messenger lipids (steroid hormones and eicosanoids) Protective-coating lipids (biological waxes)

Our entry point into a discussion of these five general types of lipids is a consideration of molecules called fatty acids. Fatty acids are structural components of all the lipids that we consider in this chapter except cholesterol, bile acids, and steroid hormones. Familiarity with the structural characteristics and physical properties of fatty acids makes it easier to understand the behavior of the many fatty-acid-containing lipids found in the human body.

19.2 TYPES OF FATTY ACIDS Fatty acids are acids that were first isolated from naturally occurring fats; hence the designation fatty acids.

A fatty acid is a naturally occurring monocarboxylic acid. Because of the pathway by which they are biosynthesized (Section 25.7), fatty acids nearly always contain an even number of carbon atoms and have a carbon chain that is unbranched. In terms of carbon chain length, fatty acids are characterized as long-chain fatty acids (C12 to C26), mediumchain fatty acids (C8 and C10), or short-chain fatty acids (C4 and C6). Fatty acids are rarely found free in nature but rather occur as part of the structure of more complex lipid molecules.

610

Chapter 19 Lipids

Saturated and Unsaturated Fatty Acids The carbon chain of a fatty acid may or may not contain carbon–carbon double bonds. On the basis of this consideration, fatty acids are classified as saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or polyunsaturated fatty acids (PUFAs). A saturated fatty acid is a fatty acid with a carbon chain in which all carbon–carbon bonds are single bonds. The structural formula for the 16-carbon SFA is H H H H H H H H H H H H H H H O A A A A A A A A A A A A A A A B HO COCOCOCOCOCOCO COCOCOCOCOCOCO CO COOH A A A A A A A A A A A A A A A H H H H H H H H H H H H H H H IUPAC name: hexadecanoic acid Common name: palmitic acid

The structural formula for a fatty acid is usually written in a more condensed form than the preceding structural formula. Two alternative structural notations for palmitic acid are O B CH3 O (CH2 )14 OCOOH

and COOH

(We first encountered line-angle structural formulas in Section 12.9.) A monounsaturated fatty acid is a fatty acid with a carbon chain in which one carbon–carbon double bond is present. In biochemically important MUFAs, the configuration about the double bond is nearly always cis (Section 13.5). Different ways of depicting the structure of a MUFA follow.

More than 500 different fatty acids have been isolated from the lipids of microorganisms, plants, animals, and humans. These fatty acids differ from one another in the length of their carbon chains, their degree of unsaturation (number of double bonds), and the positions of the double bonds in the chains.

H H A A H H H A OCP COC A AH H C H A A OCO A H H A OCO A H A CO A H H C A H A A CO A H H H H A OCO A A CO A H H H H A OC A A C H A H A OC A H H A OCO A C A H A H C KO H CO A H H H HO A OH H O B CH3 O (CH2 )7 O CHPCHO (CH2 )7 OCOOH COOH cis-9-octadecenoic acid IUPAC name: Common name: oleic acid

The fatty acids present in naturally occurring lipids almost always have the following three characteristics: 1. An unbranched carbon chain 2. An even number of carbon atoms in the carbon chain 3. Double bonds, when present in the carbon chain, in a cis configuration

The first of these structures correctly emphasizes that the presence of a cis double bond in the carbon chain puts a rigid 30⬚ bend in the chain. Such a bend affects the physical properties of a fatty acid, as we will see in Section 19.3. A polyunsaturated fatty acid is a fatty acid with a carbon chain in which two or more carbon–carbon double bonds are present. Up to six double bonds are found in biochemically important PUFAs. Fatty acids are nearly always referred to using their common names. IUPAC names for fatty acids, although easily constructed, are usually quite long. These two types of

19.2 Types of Fatty Acids

611

names for an 18-carbon PUFA containing cis double bonds in the 9 and 12 positions are as follows: IUPAC name: cis,cis-9,12-octadecadienoic acid Common name: linoleic acid

Unsaturated Fatty Acids and Double-Bond Position A numerically based shorthand system exists for specifying key structural parameters for fatty acids. In this system, two numbers separated by a colon are used to specify the number of carbon atoms and the number of carbon–carbon double bonds present. The notation 18:0 denotes a C18 fatty acid with no double bonds, whereas the notation 18:2 signifies a C18 fatty acid in which two double bonds are present. To specify double-bond positioning within the carbon chain of an unsaturated fatty acid, the preceding notation is expanded by adding the Greek capital letter delta (⌬) followed by one or more superscript numbers. The notation 18:3(⌬9,12,15) denotes a C18 PUFA with three double bonds at locations between carbons 9 and 10, 12 and 13, and 15 and 16. 18

16

15

17

13 14

10

12 11

9

7 8

5 6

3 4

COOH 2

MUFAs are usually ⌬9 acids, and the first two additional double bonds in PUFAs are generally at the ⌬12 and ⌬15 locations. [A notable exception to this generalization is the biochemically important arachidonic acid, a PUFA with the structural parameters 20:4(⌬5,8,11,14)]. Denoting double-bond locations using this “delta notation” always assumes a numbering system in which the carboxyl carbon atom is C-1. Several different “families” of unsaturated fatty acids exist. These family relationships become apparent when double-bond position is specified relative to the methyl (noncarboxyl) end of the fatty acid carbon chain. Double-bond positioning determined in this manner is denoted by using the Greek lower-case letter omega (v). An omega-3 fatty acid is an unsaturated fatty acid with its endmost double bond three carbon atoms away from its methyl end. An example of an omega-3 fatty acid is v-3

1

3

COOH

(20:5)

2

An omega-6 fatty acid is an unsaturated fatty acid with its endmost double bond six carbon atoms away from its methyl end. The following three acids all belong to the omega-6 fatty acid family. 6

v-6

COOH

1 6

v-6

(14:1) COOH

(18:2)

1 6

v-6 1

COOH

(20:3)

The structural feature common to these omega-6 fatty acids is highlighted with color in the preceding structural formulas. All the members of an omega family of fatty acids have structures in which the same “methyl end” is present. Table 19.1 gives the names and structures of the fatty acids most commonly encountered as building blocks in biochemically important lipid structures, as well as the “delta” and “omega” notations for the acids.

612

Chapter 19 Lipids

TABLE 19.1 Selected Fatty Acids of Biological Importance Structural Notation

Common Name

Structure

Saturated Fatty Acids

12:0

lauric acid

14:0

myristic acid

16:0

palmitic acid

18:0

stearic acid

20:0

arachidic acid

COOH COOH COOH COOH COOH

Monounsaturated Fatty Acids

16:1

⌬9

v-7

palmitoleic acid

18:1

⌬9

v-9

oleic acid

COOH COOH

Polyunsaturated Fatty Acids

18:2

⌬9,12

v-6

linoleic acid

18:3

⌬9,12,15

v-3

linolenic acid

20:4

⌬5,8,11,14

v-6

arachidonic acid

20:5

⌬5,8,11,14,17

v-3

EPA (eicosapentaenoic acid)

22:6

⌬4,7,10,13,16,19

v-3

DHA (docosahexaenoic acid)

EXAMPLE 19.1 Classifying Fatty Acids on the Basis of Structural Characteristics

COOH COOH COOH COOH

COOH

Classify the fatty acid with the following structural formula in the ways indicated.

COOH a. What is the type designation (SFA, MUFA, or PUFA) for this fatty acid? b. On the basis of carbon chain length and degree of unsaturation, what is the numerical shorthand designation for this fatty acid? c. To which “omega” family of fatty acids does this fatty acid belong? d. What is the “delta” designation for the carbon chain double-bond locations for this fatty acid? Solution

a. Two carbon–carbon double bonds are present in this molecule, which makes it a polyunsaturated fatty acid (PUFA). b. Eighteen carbon atoms and two carbon–carbon double bonds are present. The shorthand numerical designation for this fatty acid is thus 18:2. c. Counting from the methyl end of the carbon chain, the first double bond encountered involves carbons 6 and 7. This fatty acid belongs to the omega-6 family of fatty acids. d. Counting from the carboxyl end of the carbon chain, with C-1 being the carboxyl group, the double-bond locations are 9 and 12. This is a ⌬9,12 fatty acid.

19.3 Physical Properties of Fatty Acids

613

Practice Exercise 19.1 Classify the fatty acid with the following structural formula in the ways indicated.

COOH a. What is the type designation (SFA, MUFA, or PUFA) for this fatty acid? b. On the basis of carbon chain length and degree of unsaturation, what is the numerical shorthand designation for this fatty acid? c. To which “omega” family of fatty acids does this fatty acid belong? d. What is the “delta” designation for the carbon chain double-bond location for this fatty acid? Answers: a. MUFA (monounsaturated fatty acid); b. 12:1 fatty acid; c. omega-3 fatty acid (v-3);

d. delta-9 fatty acid (⌬9)

19.3 PHYSICAL PROPERTIES OF FATTY ACIDS

Fatty acids have low water solubilities, which decrease with increasing carbon chain length; at 30⬚C, lauric acid (12:0) has a water solubility of 0.063 g/L and stearic acid (18:0) a solubility of 0.0034 g/L. Contrast this with glucose’s solubility in water at the same temperature, 1100 g/L.

The physical properties of fatty acids, and of lipids that contain them, are largely determined by the length and degree of unsaturation of the fatty acid carbon chain. Water solubility for fatty acids is a direct function of carbon chain length; solubility decreases as carbon chain length increases. Short-chain fatty acids have a slight solubility in water. Long-chain fatty acids are essentially insoluble in water. The slight solubility of short-chain fatty acids is related to the polarity of the carboxyl group present. In longerchain fatty acids, the nonpolar nature of the hydrocarbon chain completely dominates solubility considerations. Melting points for fatty acids are strongly influenced by both carbon chain length and degree of unsaturation (number of double bonds present). Figure 19.2 shows meltingpoint variation as a function of both of these variables. As carbon chain length increases, melting point increases. This trend is related to the greater surface area associated with a longer carbon chain and to the increased opportunities that this greater surface area affords for intermolecular attractions between fatty acid molecules. A trend of particular significance is that saturated fatty acids have higher melting points than unsaturated fatty acids with the same number of carbon atoms. The greater

Figure 19.2 The melting point of a

90

fatty acid depends on the length of the carbon chain and on the number of double bonds present in the carbon chain.

80 Stearic acid

Temperature (°C)

70 60 50

Saturated fatty acids

40 30 20

Room temperature Oleic acid (1 double bond)

10 0 –10 –20

Linoleic acid (2 double bonds) Linolenic acid (3 double bonds) 4

6

8 10 12 14 16 18 20 22 24 Number of carbon atoms

614

Chapter 19 Lipids

Figure 19.3 Space-filling models of four 18-carbon fatty acids, which differ in the number of double bonds present. Note how the presence of double bonds changes the shape of the molecule.

Stearic acid (18:0)

Oleic acid (18:1)

Linoleic acid (18:2)

Linolenic acid (18:3)

the degree of unsaturation, the greater the reduction in melting points. Figure 19.2 shows this effect for the 18-carbon acids with zero, one, two, and three double bonds. Longchain saturated fatty acids tend to be solids at room temperature, whereas long-chain unsaturated fatty acids tend to be liquids at room temperature. The decreasing melting point associated with increasing degree of unsaturation in fatty acids is explained by decreased molecular attractions between carbon chains. The double bonds in unsaturated fatty acids, which generally have the cis configuration, produce “bends” in the carbon chains of these molecules (see Figure 19.3). These “bends” prevent unsaturated fatty acids from packing together as tightly as saturated fatty acids. The greater the number of double bonds, the less efficient the packing. As a result, unsaturated fatty acids always have fewer intermolecular attractions, and therefore lower melting points, than their saturated counterparts.

19.4 ENERGY-STORAGE LIPIDS: TRIACYLGLYCEROLS

Figure 19.4 An electron micrograph of adipocytes, the body’s triacylglycerol-storing cells. Note the bulging spherical shape.

With the notable exception of nerve cells, human cells store small amounts of energyproviding materials for use when energy demand is high. The most widespread energystorage material within cells is the carbohydrate glycogen (Section 18.15); it is present in small amounts in most cells. Lipids known as triacylglycerols also function within the body as energy-storage materials. Rather than being widespread, triacylglycerols are concentrated primarily in special cells (adipocytes) that are nearly filled with the material. Adipose tissue containing these cells is found in various parts of the body: under the skin, in the abdominal cavity, in the mammary glands, and around various organs (see Figure 19.4). Triacylglycerols are much more efficient at storing energy than is glycogen because large quantities of them can be packed into a very small volume. These energy-storage lipids are the most abundant type of lipid present in the human body. In terms of functional groups present, triacylglycerols are triesters; three ester functional groups are present. Recall from Section 16.11 that an ester is a compound produced from the reaction of an alcohol with a carboxylic acid. The alcohol involved in triacylglycerol formation is always glycerol, a three-carbon alcohol with three hydroxyl groups.

19.4 Energy-Storage Lipids: Triacylglycerols

615

CH2 OOH A CHOOH A CH2 OOH Glycerol

Fatty acids are the carboxylic acids involved in triacylglycerol formation. In the esterification reaction producing a triacylglycerol, a single molecule of glycerol reacts with three fatty acid molecules; each of the three hydroxyl groups present is esterified. Figure 19.5 shows the triple esterification reaction that occurs between glycerol and three molecules of stearic acid (18:0); note the production of three molecules of water as a by-product of the reaction. Two general ways to represent the structure of a triacylglycerol are Triacylglycerols do not actually contain glycerol and three fatty acids, as the block diagram for a triacylglycerol implies. They actually contain a glycerol residue and three fatty acid residues. In the formation of the triacylglycerol, three molecules of water have been removed from the structural components of the triacylglycerol, leaving residues of the reacting molecules.

O G l y c e r o l

Fatty acid

CH2 O C

R

O Fatty acid

CH O C

Ester linkage

R⬘

O Fatty acid

CH2 O C

R⬙

The first representation, a block diagram, shows the four subunits present in the structure: glycerol and three fatty acids. The second representation, a general structural formula, shows the three ester linkages present in a triacylglycerol. Each of the fatty acids is attached to glycerol through an ester linkage. Formally defined, a triacylglycerol is a lipid formed by esterification of three fatty acids to a glycerol molecule. Within the name triacylglycerol is the term acyl. An acyl group, previously defined and considered in Section 16.19, is the portion of a carboxylic acid that remains after the —OH group is removed from the carboxyl carbon atom. The structural representation for an acyl group is O B RO C O An acyl group

Thus, as the name implies, triacylglycerol molecules contain three fatty acid residues (three acyl groups) attached to a glycerol residue. An older name that is still frequently used for a triacylglycerol is triglyceride. The triacylglycerol produced from glycerol and three molecules of stearic acid (as in Figure 19.5) is an example of a simple triacylglycerol. A simple triacylglycerol

Figure 19.5 Structure of the simple triacylglycerol produced from the triple esterification reaction between glycerol and three molecules of stearic acid (18:0 acid). Three molecules of water are a by-product of this reaction.

H H C O H

O H O C

H

O

H C O

C

O H C O H

H O C

O H C O

O H C O H

H O C

H Glycerol

+ H2O

C

+ H2O

O H C O

C

+ H2O

H Three fatty acids

Triester of glycerol

Three water molecules

616

Chapter 19 Lipids

Figure 19.6 Structure of a mixed triacylglycerol in which three different fatty acid residues are present.

H

O

H C O

C

(18:0 fatty acid)

O H C O

(18:1 fatty acid)

C

O H C O

(18:2 fatty acid)

C

H

is a triester formed from the esterification of glycerol with three identical fatty acid molecules. If the reacting fatty acid molecules are not all identical, then the result is a mixed triacylglycerol. A mixed triacylglycerol is a triester formed from the esterification of glycerol with more than one kind of fatty acid molecule. Figure 19.6 shows the structure of a mixed triacylglycerol in which one fatty acid is saturated, another monounsaturated, and the third polyunsaturated. Naturally occurring simple triacylglycerols are rare. Most biochemically important triacylglycerols are mixed triacylglycerols.

EXAMPLE 19.2 Drawing the Structural Formula of a Triacylglycerol

Draw the structural formula of the triacylglycerol produced from the reaction between glycerol and three molecules of myristic acid. Solution

From Table 19.1 we note that myristic acid is the 14:0 fatty acid. Draw the structure of glycerol and then place three molecules of myristic acid alongside the glycerol. The fatty acid placements should be such that their carboxylic groups are lined up alongside the hydroxyl groups of glycerol. Form an ester linkage between each carboxylic group and a glycerol hydroxyl group with the accompanying production of a water molecule. O CH2

OH

HO

C

O CH2 O

O CH

OH + HO

C

O CH

O

O CH2

OH

Glycerol

HO

C

Fatty acids (14:0)

C

C

+ 3H2O

O CH2 O

C

Triacylglycerol

Practice Exercise 19.2 Draw the structural formula of the triacylglycerol produced from the reaction between glycerol and three molecules of lauric acid.

19.4 Energy-Storage Lipids: Triacylglycerols

Answer:

O CH2

OH

HO

C

O CH2 O

O CH

OH + HO

C

OH

HO

Glycerol

C

Fatty acids (12:0)

C O

CH

O

O CH2

617

+ 3H2O

C O

CH2 O

C

Triacylglycerol

Fats and Oils

B

F

Petroleum oils (Section 12.15) are structurally different from lipid oils. The former are mixtures of alkanes and cycloalkanes. The latter are mixtures of triesters of glycerol.

Fats are naturally occurring complex mixtures of triacylglycerol molecules in which many different kinds of triacylglycerol molecules are present. Oils are also naturally occurring complex mixtures of triacylglycerol molecules in which there are many different kinds of triacylglycerol molecules present. Given that both are triacylglycerol mixtures, what distinguishes a fat from an oil? The answer is physical state at room temperature. A fat is a triacylglycerol mixture that is a solid or a semi-solid at room temperature (25⬚C). Generally, fats are obtained from animal sources. An oil is a triacylglycerol mixture that is a liquid at room temperature (25⬚C). Generally, oils are obtained from plant sources. Because they are mixtures, no fat or oil can be represented by a single specific chemical formula. Many different fatty acids are represented in the triacylglycerol molecules present in the mixture. The actual composition of a fat or oil varies even for the species from which it is obtained. Composition depends on both dietary and climatic factors. For example, fat obtained from corn-fed hogs has a different overall composition than fat obtained from peanut-fed hogs. Flax seed grown in warm climates gives oil with a different composition from that obtained from flax seed grown in colder climates. Additional generalizations and comparisons between fats and oils follow. 1. Fats are composed largely of triacylglycerols in which saturated fatty acids predominate, although some unsaturated fatty acids are present. Such triacylglycerols can pack closely together because of the “linearity” of their fatty acid chains (Figure 19.7a), thus causing the higher melting points associated with fats. Oils contain triacylglycerols with larger amounts of mono- and polyunsaturated fatty acids than those in fats. Such triacylglycerols cannot pack as tightly together because of “bends” in their fatty acid chains (Figure 19.7b). The result is lower melting points. 2. Fats are generally obtained from animals; hence the term animal fat. Although fats are solids at room temperature, the warmer body temperature of the living animal

Figure 19.7 Representative triacylglycerols from (a) a fat and (b) an oil.

(a)

(b)

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Dietary Oil or Fat

Figure 19.8 Percentages of saturated, monounsaturated, and polyunsaturated fatty acids in the triacylglycerols of various dietary fats and oils.

Canola oil Safflower oil Sunflower oil Avocado oil Corn oil Olive oil Soybean oil Peanut oil Cottonseed oil Lard Palm oil Beef tallow Butterfat Coconut oil

6% 58% 9% 13% 78% 11% 20% 69% 12% 74% 13% 25% 62% 14% 77% 15% 24% 61% 18% 48% 27% 19% 54% 41% 47% 51% 39% 52% 44% 66% 92% Saturated

All oils, even polyunsaturated oils, contain some saturated fatty acids. All fats, even highly saturated fats, contain some unsaturated fatty acids.

Monounsaturated

36%

14% 9% 34%

30%

Polyunsaturated

12% 10% 4% 4% 6% 2%

keeps the fat somewhat liquid (semi-solid) and thus allows for movement. Oils typically come from plants, although there are also fish oils. A fish would have some serious problems if its triacylglycerols “solidified” when it encountered cold water. 3. Pure fats and pure oils are colorless, odorless, and tasteless. The tastes, odors, and colors associated with dietary plant oils are caused by small amounts of other naturally occurring substances present in the plant that have been carried along during processing. The presence of these “other” compounds is usually considered desirable. Figure 19.8 gives the percentages of saturated, monounsaturated, and polyunsaturated fatty acids found in common dietary oils and fats. In general, a higher degree of fatty acid unsaturation is associated with oils than with fats. A notable exception to this generalization is coconut oil, which is highly saturated. This oil is a liquid not because it contains many double bonds within the fatty acids but because it is rich in shorter-chain fatty acids, particularly lauric acid (12:0).

19.5 DIETARY CONSIDERATIONS AND TRIACYLGLYCEROLS

A grain- and vegetable-rich diet that contains small amounts of extravirgin olive oil (three to four teaspoons daily) has been found to help people with high blood pressure reduce the amount of blood pressure medication they require, on average, by 48%. Substitution of sunflower oil for the olive oil resulted in only a 4% reduction in medication dosage. The blood-pressure-reduction benefits of olive oil do not relate to the triacylglycerols present but rather come from “other” compounds naturally present, namely from antioxidant polyphenols olive oil contains. These antioxidants help promote the relaxation of blood vessels.

In the past two decades, considerable research has been carried out concerning the role of dietary factors as a cause of disease (obesity, diabetes, cancer, hypertension, and atherosclerosis). Numerous studies have shown that, in general, nations whose citizens have high dietary intakes of triacylglycerols (fats and oils) tend to have higher incidences of heart disease and certain types of cancers. This is the reason for concern that the typical American diet contains too much fat and the call for Americans to reduce their total dietary fat intake. Contrary to the general trend, however, there are several areas of the world where high dietary fat intake does not translate into high risks for cardiovascular disease, obesity, and certain types of cancers. These exceptions, which include some Mediterranean countries and the Inuit people of Greenland, suggest that relationships between dietary triacylglycerol intake and risk factors for disease involve more than simply the total amount of triacylglycerols consumed.

“Good Fats” Versus “Bad Fats” In dietary discussions, the term fat is used as a substitute for the term triacylglycerol. Thus a dietary fat can be either a “fat” or an “oil.” Ongoing studies indicate that both the type of dietary fat consumed and the amount of dietary fat consumed are important factors in determining human body responses to dietary fat. Current dietary fat recommendations are that people limit their total fat intake to 30% of total calories—with up to 15% coming from monounsaturated fat, up to 10% from polyunsaturated fat, and less than 10% from saturated fats.

19.5 Dietary Considerations and Triacylglycerols

Freshly pressed extra-virgin olive oil contains a compound that has the same pharmacological activity as the over-the-counter pain reliever ibuprofen (Section 16.4). This finding suggests a possible explanation for some of the various health benefits attributed to a Mediterranean diet that typically is rich in olive oil. It is estimated that this olive oil compound, called oleocanthal, is present in a typical Mediterranean diet in an amount equivalent to about 10% of the ibuprofen dose recommended for headache relief.

B O

HO H

O G H H

B

O

B O Oleocanthal

Figure 19.9 Fish that live in deep, cold water—mackerel, herring, tuna, and salmon—are better sources of omega-3 fatty acids than other fish.

These recommendations imply correctly that different types of dietary fat have different effects. In simplified terms, research studies indicate that saturated fats are “bad fat,” monounsaturated fats are “good fat,” and polyunsaturated fats can be both “good fat” and “bad fat.” In the latter case, fatty acid omega type (Section 19.2) becomes important, a situation addressed later in this section. Studies indicate that saturated fat can increase heart disease risk, that monounsaturated fat can decrease both heart disease and breast cancer risk, and that polyunsaturated fat can reduce heart disease risk but promote the risk of certain types of cancers. Referring to Figure 19.8, note the wide variance in the three general types of fatty acids (SFAs, MUFAs, and PUFAs) present in various kinds of dietary fats. Dietary fats high in “good” monounsaturated fatty acids include olive, avocado, and canola oils. Monounsaturated fatty acids help reduce the stickiness of blood platelets. This helps prevent the formation of blood clots and may also dissolve clots once they form. Many people do not realize that most tree nuts and peanuts are good sources of MUFAs. The Chemical Connections feature on page 620 looks at recent research on the fat content of nuts.

Omega-3 and Omega-6 Fatty Acids In the 1980s, researchers found that the Inuit people of Greenland exhibit a low incidence of heart disease despite having a diet very high in fat. This contrasts markedly with studies on the U.S. population, which show a correlation between a high-fat diet and a high incidence of heart disease. What accounts for the difference between the two peoples? The Inuit diet is high in omega-3 fatty acids (from fish), and the U.S. diet is high in omega-6 fatty acids (from plant oils). An American consumes about double the amount of omega-6 fatty acids and half the amount of omega-3 fatty acids that an Inuit consumes. Several large studies now confirm that benefits can be derived from eating several servings of fish each week. The choice of fish is important, however. Not all fish are equal in omega-3 fatty acid content. Cold-water fish, also called fatty fish because of the extra amounts of fat they have for insulation against the cold, contain more omega-3 acids than leaner, warm-water fish. Fatty fish include albacore tuna, salmon, and mackerel (see Figure 19.9). Leaner, warm-water fish, which include cod, catfish, halibut, sole, and snapper, do not appear to offer as great a positive effect on heart health as do their “fatter” counterparts. (Note that most of the fish used in fish and chips (e.g., cod, halibut) is on the low end of the omega-3 scale.) Table 19.2 gives the actual omega-3 fatty acid concentrations associated with various kinds of cold-water fish.

TABLE 19.2 Omega-3 Fatty Acid Amounts Associated with Various Kinds of Cold-Water Fish

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Per 3.5-oz. Serving (raw)

Omega-3s (grams)*

mackerel albacore tuna herring, Atlantic anchovy salmon, wild king (Chinook) salmon, wild sockeye (red) tuna, bluefin salmon, wild pink salmon, wild Coho (silver) oysters, Pacific salmon, farm-raised Atlantic swordfish trout, rainbow

2.3 2.1 1.6 1.5 1.4 1.2 1.2 1.0 0.8 0.7 0.6 0.6 0.6

*Omega-3 content of fish can vary depending on harvest location and time of year.

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The Fat Content of Tree Nuts and Peanuts

People who bypass the nut tray at holiday parties usually believe in a myth—that nuts are unhealthful high-fat foods. Indeed, nuts are high-fat food. However, the fat is “good fat” rather than “bad fat” (Section 19.5); that is, the fatty acids present are MUFAs and PUFAs rather than SFAs. In most cases, a handful of nuts is better for you than a cookie or bagel. Numerous studies now indicate that eating nuts can have a strong protective effect against coronary heart disease. The most improvement comes from adding small amounts of nuts— an ounce (3–4 teaspoons)—to the diet five or more times a week. Raw, dry-roasted, or lightly salted varieties are best. The recommendation of only one ounce of nuts per day relates to the high calorie content of nuts, which is 160 to 200 calories per ounce. The number of nuts and number of calories per ounce for common types of nuts is as follows: Nuts

The amount of fat present in nuts ranges from 74% in the macadamia nut, 68% in pecans, and 63% in hazelnuts to around 50% in nuts such as the almond, cashew, peanut, and pistachio, as is shown in the table below. The different fatty acid fractions (SFAs, MUFAs, and PUFAs) present in nuts also vary, but with definite trends. Unsaturated fatty acids always significantly dominate saturated fatty acids. The unsaturation/saturation ratio is highest for hazelnuts (11.9), pecans (10.9), walnuts (9.0), and almonds (9.0) and is lowest for cashews (3.9). Their low amounts of saturated fatty acids are not the only reason why nuts help reduce the risk of coronary heart disease. Nuts also offer valuable antioxidant vitamins, minerals, and plant fiber protein. The protein content is highest (18%–26%) in the cashew, pistachio, almond, and peanut; here the amount of protein is about the same as in meat, fish, and cheese. The carbohydrate content of nuts is relatively low, less than 10% in most cases. An unexpected discovery involving the anticancer drug Taxol and hazelnuts was made in the year 2000. The active chemical component in this drug, paclitaxel, was found in hazelnuts. It was the first report of this potent chemical being found in a plant other than in the bark of the Pacific yew tree, a slow-growing plant found in limited quantities in the Pacific Northwest. Although the amount of the chemical found in a hazelnut tree is about one-tenth that found in yew bark, the effort required to extract paclitaxel from these sources is comparable. Because hazelnut trees are more common, this finding could reduce the cost of the commercial drug and make it more readily available.

Calories

18 cashews 20 peanuts 47 pistachios 24 almonds 14 walnut halves 8 Brazil nuts 12 hazelnuts 15 pecan halves 12 macadamias

160 160 160 166 180 186 188 190 200

Fat and Fatty Acid Composition of Selected Nuts Total Fat (percentage of weight) almonds cashews hazelnuts macadamias peanuts pecans pistachios walnuts

52 46 63 74 49 68 48 62

SFA MUFA PUFA (percentage of total fat) 10 20 8 16 15 8 13 10

68 62 82 82 51 66 72 24

22 18 10 2 34 26 15 66

UFA/SFA Ratio 9.0 3.9 11.9 5.4 5.7 10.9 6.6 9.0

Essential Fatty Acids An essential fatty acid is a fatty acid needed in the human body that must be obtained from dietary sources because it cannot be synthesized within the body, in adequate amounts, from other substances. There are two essential fatty acids: linoleic acid and linolenic acid. Linoleic acid (18:2) is the primary member of the omega-6 acid family, and linolenic acid (18:3) is the primary member of the omega-3 acid family. Their structures were given in Table 19.1. These two acids (1) are needed for proper membrane structure and (2) serve as starting materials for the production of several nutritionally important longer-chain omega-6

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TABLE 19.3 Biochemically Important Omega-3 and Omega-6 Fatty Acids

Omega-3 Acids

Omega-6-Acids

linolenic acid (18:3) (lin-oh-LEN-ic)

linoleic acid (18:2) (lin-oh-LAY-ic)

eicosapentaenoic acid (20:5) (EYE-cossa-PENTA-ee-NO-ic)

arachidonic acid (20:4) (a-RACK-ih-DON-ic)

docosahexaenoic acid (20:6) (DOE-cossa-HEXA-ee-NO-ic)

In 2001 the FDA gave approval for manufacturers of baby formula to add the fatty acids DHA (docosahexaenoic acid) and AA (arachidonic acid) to infant formulas. Human breast milk naturally contains these acids, which are important in brain and vision development. Because not all mothers can breast-feed, health officials regulate the ingredients in infant formula so that formula-fed babies get the next best thing to mother’s milk.

and omega-3 acids. When these two acids are missing from the diet, the skin reddens and becomes irritated, infections and dehydration are likely to occur, and the liver may develop abnormalities. If the fatty acids are restored, then the conditions reverse themselves. Infants are especially in need of these acids for their growth. Human breast milk has a much higher percentage of the essential fatty acids than cow’s milk. Linoleic acid is the starting material for the biosynthesis of arachidonic acid. Linoleic acid (18:2) 9: arachidonic acid (20:4) Omega-6 fatty acids

Arachidonic acid is the major starting material for eicosanoids (Section 19.13), substances that help regulate blood pressure, clotting, and several other important body functions. Linolenic acid is the starting material for the biosynthesis of two additional omega-3 fatty acids. Linolenic acid (18:3) 9: EPA (20:5) 9: DHA (22:6) Omega-3 fatty acids

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are important constituents of the communication membranes of the brain and are necessary for normal brain development. EPA and DHA are also active in the retina of the eye. Table 19.3 gives pronunciation guidelines for the names of the two essential fatty acids and of the other acids mentioned that are biosynthesized from them.

Fat Substitutes (Artificial Fats) In response to consumer demand for low-fat, low-calorie foods, food scientists have developed several types of “artificial fats.” Such substances replicate the taste, texture, and cooking properties of fats but are themselves not lipids. See the Chemical Connections feature on page 624 for further discussion of this topic.

19.6 CHEMICAL REACTIONS OF TRIACYLGLYCEROLS The chemical properties of triacylglycerols (fats and oils) are typical of esters and alkenes because these are the two functional groups present in triacylglycerols. Four important triacylglycerol reactions are hydrolysis, saponification, hydrogenation, and oxidation. B

F

Naturally occurring mono- and diacylglycerols are seldom encountered. Synthetic mono- and diacylglycerols are used as emulsifiers in many food products. Emulsifiers prevent suspended particles in colloidal solutions (Section 8.7) from coalescing and settling. Emulsifiers are usually present in so-called fat-free cakes and other fat-free products.

Hydrolysis Hydrolysis of a triacylglycerol is the reverse of the esterification reaction by which it was formed (see Figure 19.5). Triacylglyercol hydrolysis, when carried out in a laboratory setting, requires the presence of an acid or a base. Under acidic conditions, the hydrolysis products are glycerol and fatty acids. Under basic conditions, the hydrolysis products are glycerols and fatty acid salts. Within the human body, triacylglycerol hydrolysis occurs during the process of digestion. Such hydrolysis requires the help of enzymes (protein catalysts; Section 21.1) produced by the pancreas. These enzymes cause the triacylglycerol to be hydrolyzed in a

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Figure 19.10 Complete and partial hydrolysis of a triacylglycerol. (a) Complete hydrolysis of a triacylglycerol produces glycerol and three fatty acid molecules. (b) Partial hydrolysis (during digestion) of a triacylglycerol produces a monoacylglycerol and two fatty acid molecules.

(a) Complete hydrolysis Water H O H H

O

H C O

C

O

H H C O H Water H O H

HO

Steam O

O H C O

C

H+

C

H C O H

HO

C

Water H O H O

O H C O

H C O H

C

HO

C

H

H

(b) Partial hydrolysis Water H O H H

O

H C O

C

O

H H C O H

HO

C

Enzymes O H C O

O H C O

C

C

Water H O H O

O H C O

H C O H

C

HO

C

H

H

stepwise fashion. First, one of the outer fatty acids is removed, then the other outer one, leaving a monoacylglycerol. In most cases this is the end product of the initial digestion (hydrolysis) of the triacylglycerol. Sometimes, enzymes remove all three fatty acids, leaving a free molecule of glycerol. In situations where all three fatty acids are removed the hydrolysis process is referred to as complete hydrolysis, which is depicted in Figure 19.10a. If one or more of the fatty acid residues remains attached to the glycerol, the hydrolysis process is called partial hydrolysis (see Figure 19.10b).

EXAMPLE 19.3 Writing a Structural Equation for the Hydrolysis of a Triacylglycerol

Write an equation for the acid-catalyzed hydrolysis of the following triacylglycerol. O CH2 O

C O

CH

O

C O

CH2 O

C

19.6 Chemical Reactions of Triacylglycerols

623

Solution

Three water molecules are required for the hydrolysis, one to interact with each of the ester linkages present in the triacylglycerol. Breaking of the three ester linkages produces four product molecules: glycerol and three fatty acids. O CH2 O

O

C

CH2

O CH

O

O CH

C

OH + HO

O CH2 O

C

HO

H+

+3H O H Water

C

OH

O

C

CH2 OH

Triacylglycerol

C

HO

Glycerol

Fatty acids

Practice Exercise 19.3 Write a structural equation for the acid-catalyzed hydrolysis of the following triacylglycerol. O CH2 O

C O

CH

O

C O

CH2 O

C

O

Answer:

CH2 O

O

C

CH2

O CH

O

C

+ 3H2O

OH

HO

O

H+ CH

OH + HO

O CH2 O

B

F

Recall from Section 16.9 the structural difference between a carboxylic acid and a carboxylic acid salt.

C

C

C O

CH2

OH

HO

C

Saponification

O B R O CO OH

O B R O CO O⫺ Na⫹

Saponification (Section 16.16) is a reaction carried out in an alkaline (basic) solution. For fats and oils, the products of saponification are glycerol and fatty acid salts. The overall reaction of triacylglycerol saponification can be thought of as occurring in two steps. The first step is the hydrolysis of the ester linkages to produce glycerol and three fatty acid molecules:

Carboxylic acid

Carboxylic acid salt

Fat or oil ⫹ 3H2O 9: 3 fatty acids ⫹ glycerol

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The second step involves a reaction between the fatty acid molecules and the base (usually NaOH) in the alkaline solution. This is an acid–base reaction that produces water plus salts: 3 Fatty acids ⫹ 3NaOH 9: 3 fatty acid salts ⫹ 3H2O Saponification of animal fat is the process by which soap was made in pioneer times. Soap making involved heating lard (fat) with lye (ashes of wood, an impure form of KOH). Today most soap is prepared by hydrolyzing fats and oils (animal fat and coconut oil) under high pressure and high temperature. Sodium carbonate is used as the base. The cleansing action of soap is related to the structure of the carboxylate ions present in the fatty acid salts of soap and the fact that these ions readily participate in micelle formation. A micelle is a spherical cluster of molecules in which the polar portions of the molecules are on the surface, and the nonpolar portions are located in the interior. The Chemical Connections feature on page 625 discusses micelle formation further as it relates to the cleansing action of soap.

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Artificial Fat Substitutes

Artificial sweeteners (sugar substitutes) have been an accepted part of the diet of most people for many years. New since the 1990s are artificial fats—substances that create the sensations of “richness” of taste and “creaminess” of texture in food without the negative effects associated with dietary fats (heart disease and obesity). Food scientists have been trying to develop fat substitutes since the 1960s. Now available for consumer use are two types of fat substitutes: calorie-reduced fat substitutes and caloriefree substitutes. They differ in their chemical structures and therefore in how the body handles them. Simplesse, the best-known calorie-reduced fat substitute, received FDA marketing approval in 1990. It is made from the protein of fresh egg whites and milk by a procedure called microparticulation. This procedure produces tiny, round protein particles so fine that the tongue perceives them as a fluid rather than as the solid they are. Their fineness creates a sensation of smoothness, richness, and creaminess on the tongue. In the body, Simplesse is digested and absorbed, contributing to energy intake. But 1 g of Simplesse provides 1.3 cal, compared with the 9 cal provided by 1 g of fat. Simplesse is used only to replace fats in formulated foods such as salad dressings, cheeses, sour creams, and other dairy products. Simplesse is unsuitable for frying or baking because it turns rubbery or rigid (gels) when heated. Consequently, it is not available for home use. Olestra, the best-known calorie-free fat substitute, received FDA marketing approval in 1996. It is produced by heating cottonseed and/or soybean oil with sucrose in the presence of methyl alcohol. Chemically, olestra has a structure somewhat similar to that of a triacylglycerol; sucrose takes the place of the glycerol molecule, and six to eight fatty acids are attached by ester linkages to it rather than the three fatty acids in a triacyl-

CH2OOOC(O)EHEHEHEHE O HEHEHEHEH(O)COO HEHEHEHEH(O)COO

HEHEHEHEH(O)COOOCH2

O

OOC(O)EHEHEHEHE O OOC(O)EHEHEHEHE CH2OOOC(O)EHEHEHEHE

HEHEHEHEH(O)COO Olestra

glycerol. Unlike triacylglycerols, however, olestra cannot be hydrolyzed by the body’s digestive enzymes and therefore passes through the digestive tract undigested. Olestra looks, feels, and tastes like dietary fat and can substitute for fats and oils in foods such as shortenings, oils, margarines, snacks, ice creams, and other desserts. It has the same cooking properties as fats and oils. In the digestive tract, Olestra interferes with the absorption of both dietary and body-produced cholesterol; thus it may lower total cholesterol levels. A problem with its use is that it also reduces the absorption of the fat-soluble vitamins A, D, E, and K. To avoid such depletion, Olestra is fortified with these vitamins. Another problem with Olestra use is that in some individuals it can cause gastrointestinal irritation and/or diarrhea. All products containing Olestra must carry the following label: “Olestra may cause abdominal cramping and loose stools. Olestra inhibits the absorption of some vitamins and other nutrients. Vitamins A, D, E, and K have been added.”

19.6 Chemical Reactions of Triacylglycerols

625

Hydrogenation Hydrogenation is a chemical reaction we first encountered in Section 13.9. It involves hydrogen addition across carbon–carbon multiple bonds, which increases the degree of saturation as some double bonds are converted to single bonds. With this change, there is a corresponding increase in the melting point of the substance. Hydrogenation involving just one carbon–carbon bond within a fatty acid residue of a triacylglycerol can be diagrammed as follows: , CH2 O CH2 O CHP CHO CH2 O CH2 , ⫹ H2

, CH2 O CH2 O CH2 O CH2 O CH2 O CH2 ,

Portion of an unsaturated fatty acid residue in a triacylglycerol containing one double bond

The double bond has been converted to a single bond; the degree of saturation has increased

The structural equation for the complete hydrogenation of a triacylglycerol in which all three fatty acid residues are oleic acid (18:1) is shown in Figure 19.11. Many food products are produced via partial hydrogenation. In partial hydrogenation some, but not all, of the double bonds present are converted into single bonds. In this manner, liquids (usually plant oils) are converted into semi-solid materials. Peanut butter is produced from peanut oil through partial hydrogenation. Solid cooking shortenings and stick margarine are produced from liquid plant oils through partial hydrogenation. Soft-spread margarines are also partial-hydrogenation products. Here, the extent of hydrogenation is carefully controlled to make the margarine soft at refrigerator temperatures (4⬚C). Concern has arisen about food products obtained from hydrogenation processes because the hydrogenation process itself converts some cis double bonds within fatty acid residues into trans double bonds producing trans unsaturated fatty acids. The Chemical Connections feature on page 626 explores this issue further.

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The Cleansing Action of Soap

The cleansing action of soap is directly related to the structure of the carboxylate ions present in soap within fatty acid salts. Their structure is such that they exhibit a “dual polarity.” The hydrocarbon portion of the carboxylate ion is nonpolar, and the carboxyl portion is polar. This dual polarity for the fatty acid salt sodium stearate, which is representative of all fatty acid salts present in soap, is as follows:

– COO– COO COO– COO–

COO–

COO–

COO–

COO–

Grease

COO–

COO–

COO–

COO–

COO–

COO–

⫺

⫹

COO Na Nonpolar portion

Polar portion

Soap solubilizes oily and greasy materials in the following manner: The nonpolar portion of the carboxylate ion dissolves in the nonpolar oil or grease, and the polar carboxyl portion maintains its solubility in the polar water. The penetration of the oil or grease by the nonpolar end of the carboxylate ion is followed by the formation of micelles (see the accompanying diagram). The carboxyl groups (the micelle exterior) and water molecules are attracted to each other, causing the solubilizing of the micelle. The micelles do not combine into larger drops because their surfaces are all negatively charged, and like charges repel each other. The water-soluble micelles are subsequently rinsed away, leaving a material devoid of oil and grease.

COO– COO–

COO– COO– COO– COO–

Fatty acid micelle

For most cleansing purposes, synthetic detergents have largely replaced soaps. The basis of the cleansing action of synthetic detergents is very similar to that of soaps because their structures are very similar. The structure of the sodium salt of a benzene sulfonic acid is typical of the types of molecules used in detergents. O B S OO⫺ Na⫹ B O

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Figure 19.11 Structural equation for the complete hydrogenation of a triacylglycerol with oleic acid (18:1) fatty acid residues.

H

O

H C O

C

(18:1)

O H C O

H

O

H C O

C

O

Hydrogenation

C

H C O

(18:1)

(18:0)

C

(18:0)

3H2 O

O H C O

C

(18:1)

C

(18:0)

H

H

c

H C O

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Trans Fatty Acids and Blood Cholesterol Levels

All current dietary recommendations stress reducing saturated fat intake. In accordance with such recommendations, many people have switched from butter to margarine and now use partially hydrogenated vegetable oils rather than animal fat for cooking. However, recent studies suggest that partially hydrogenated products also play a role in raising blood cholesterol levels. Why would this be so? It is now known that when triacylglycerols are subjected to partial hydrogenation (Section 19.6) two types of changes occur in the fatty acid residues present: (1) some of the cis double bonds present are converted to single bonds (the objective of the process), and (2) some of the remaining cis double bonds are converted to trans double bonds (an unanticipated result of the process). These latter cis–trans conversions affect the general shape of the fatty acid residues present in triacylglycerols, which in turn affects the biochemical behavior of the triacylglycerols. In the 18:2 (cis, cis)

18:2 (trans, trans)

18:0

O OH

O

O OH

OH

preceding diagram, note how conversion of a cis,cis-18:2 fatty acid to a trans,trans-18:2 fatty acid affects molecular shape. The trans,trans-18:2 fatty acid has a shape very much like that of an 18:0 saturated fatty acid (the structure on the right). Studies show that fatty acids with trans double bonds affect blood cholesterol levels in a manner similar to saturated fatty acids. Trans fatty acids (trans fat) make up approximately 5% of the fat intake in the typical diet in the United States, and the amount of trans fat a person consumes depends on the amount of fat eaten and on the types of foods selected. The best example of a trans fat food may be stick margarine, but it is also found in crackers, cookies, pastries, and deep-fried fast foods. Spreadable margarine in tubs, though, contains little if any trans fat. Beginning in 2006, the U.S. Food and Drug Administration (FDA) requires that the trans fat content of a food be included in the nutrition facts panel found on all food products. Prior to this rule change, the only way consumers could determine whether a food included trans fat was to look for the word hydrogenated on the list of ingredients. A food that lists partially hydrogenated oils among its first three ingredients usually contains substantial amounts of trans fatty acids as well as some saturated fat. A label of “zero grams trans fat per serving” on a product does not mean the product is absolutely trans-fat free. FDA regulations allow trans fat levels of less than 0.5 gram per serving to be labeled as 0 grams per serving. The health implications of trans fatty acids is an area of active research; many answers are yet to be found. Preliminary studies indicate that trans fat raises bad (LDL) cholesterol, but it does not raise good (HDL) cholesterol. Saturated fat, on the other hand, raises both bad and good cholesterol. Thus, just as too much saturated fat isn’t healthy, too much trans fat is also not healthy. Recommendations are that total fat intake be limited to 30% of daily calories and that combined saturated fat and trans fat intake should be limited to 10% or less of daily calories.

19.6 Chemical Reactions of Triacylglycerols

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Oxidation The carbon–carbon double bonds present in the fatty acid residues of a triacylglycerol are subject to oxidation with molecular oxygen (from air) as the oxidizing agent. Such oxidation breaks the carbon–carbon bonds, producing both aldehyde and carboxylic acid products. B

F

Antioxidants are compounds that are easily oxidized. When added to foods, they are more easily oxidized than the food. Thus they prevent the food from being oxidized (see Section 14.14).

EXAMPLE 19.4 Determining the Products for Reactions That Triacylglycerols Undergo

O CHP CHO

Oxidation

O O B B O C OH ⫹ H O C O

Unsaturated fatty acids

Short-chain aldehydes

Oxidation

O O B B O C O OH ⫹ HO O C O Short-chain carboxylic acids

The short-chain aldehydes and carboxylic acids so produced often have objectionable odors, and fats and oils containing them are said to have become rancid. To avoid this unwanted oxidation process, commercially prepared foods containing fats and oils nearly always contain antioxidants—substances that are more easily oxidized than the food. Two naturally occurring antioxidants are vitamin C (Section 21.12) and vitamin E (Section 21.13). Two synthetic oxidation inhibitors are BHA and BHT (Section 14.14). In the presence of air, antioxidants, rather than food, are oxidized.

Using words rather than structural formulas, characterize the products formed when the following triacylglycerol undergoes the reactions listed. H

O

H C O

C

(18:0 fatty acid residue)

O H C O

C

(18:1 fatty acid residue)

O H C O

C

(18:2 fatty acid residue)

H

a. Complete hydrolysis c. Complete hydrogenation

b. Complete saponification using NaOH

Solution

a. When a triacylglycerol undergoes complete hydrolysis, there are four organic products: glycerol and three fatty acids. For the given triacylglycerol the products are glycerol, an 18:0 fatty acid, an 18:1 fatty acid, and an 18:2 fatty acid. Three molecules of water are also consumed. b. When a triacylglycerol undergoes complete saponification, there are four organic products: glycerol and three fatty acid salts. For the given triacylglycerol, with NaOH as the base involved in the saponification, the products are glycerol, the sodium salt of the 18:0 fatty acid, the sodium salt of the 18:1 fatty acid, and the sodium salt of the 18:2 fatty acid. c. Complete hydrogenation will change the given triacylglycerol into a triacylglycerol in which all three fatty acid residues are 18:0 fatty acid residues. That is, all of the fatty acid residues are completely saturated (there are no carbon–carbon double bonds).

Practice Exercise 19.4 Using words rather than structural formulas, characterize the organic products formed when the following triacylglycerol undergoes the reactions listed. (continued)

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Chapter 19 Lipids

H

O

H C O

C

(18:2 fatty acid residue)

O H C O

(18:1 fatty acid residue)

C

O H C O

(18:2 fatty acid residue)

C

H

a. Complete hydrolysis c. Complete hydrogenation

b. Complete saponification using NaOH

Answers: a. Four products: glycerol and three fatty acids; b. Four products: glycerol and three fatty acid salts; c. One product: a triacylglycerol in which all fatty acid residues are saturated (18:0) residues

Classification Schemes for Fatty Acid Residues Present in Triacylglycerols FATTY ACIDS Most contain an even number of carbon atoms. Carbon chain length is up to 24 carbon atoms. Classification Based on Degree of Unsaturation

SATURATED

MONOUNSATURATED

No double bonds are present in the carbon chain. Dietary effect is an increase in heart disease risk.

One double bond is present in the carbon chain. Dietary effect is a decrease in heart disease risk.

Classification Based on Configuration of Double Bond

CIS Naturally occurring fatty acids generally contain cis double bonds.

TRANS Hydrogenation converts some cis double bonds to trans double bonds. Trans fatty acids have effects on blood chemistry similar to those of saturated fatty acids.

POLYUNSATURATED Two or more double bonds are present in the carbon chain. Dietary effect is “mixed”; there have been several conflicting studies relative to heart disease risk.

Classification Based on Location of Double Bond

OMEGA-3 First double bond is three carbons away from the CH3 end of the carbon chain. Linolenic acid (18:3) is the primary member of this family.

OMEGA-6 First double bond is six carbons away from the CH3 end of the carbon chain. Linoleic acid (18:2) is the primary member of this family.

19.7 Membrane Lipids: Phospholipids

629

Perspiration generated by strenuous exercise or by “hot and muggy” climatic conditions contains numerous triacylglycerols (oils). Rapid oxidation of these oils, promoted by microorganisms on the skin, generates the body odor that accompanies most “sweaty” people (see Figure 19.12). The Chemistry at a Glance on page 628 contains a summary of the terminology used in characterizing the properties of the fatty acid residues that are part of the structure of triacylglycerols (fats and oils). Figure 19.12 The oils (triacylglycerols) present in skin perspiration rapidly undergo oxidation. The oxidation products, short-chain aldehydes and short-chain carboxylic acids, often have strong odors.

An aminodialcohol contains two hydroxyl groups, —OH, and an amino group, —NH2.

19.7 MEMBRANE LIPIDS: PHOSPHOLIPIDS All cells are surrounded by a membrane that confines their contents. Up to 80% of the mass of a cell membrane can be lipid materials; the rest is primarily protein. It is membranes that give cells their individuality by separating them from their environment. There are three common types of membrane lipids: phospholipids, sphingoglycolipids, and cholesterol. We consider phospholipids in this section and the other two types of membrane lipids in the next two sections. Phospholipids are the most abundant type of membrane lipid. A phospholipid is a lipid that contains one or more fatty acids, a phosphate group, a platform molecule to which the fatty acid(s) and the phosphate group are attached, and an alcohol that is attached to the phosphate group. The platform molecule on which a phospholipid is built may be the 3-carbon alcohol glycerol or a more complex C18 aminodialcohol called sphingosine. Glycerol-based phospholipids are called glycerophospholipids, and those based on sphingosine are called sphingophospholipids. The general block diagrams for a glycerophospholipid and a sphingophospholipid are as follows: G l y c e r o l

Fatty acid

Sphingosine

Fatty acid

Phosphate

Fatty acid

Alcohol

Glycerophospholipid

Phosphate

Alcohol

Sphingophospholipid

Glycerophospholipids A glycerophospholipid is a lipid that contains two fatty acids and a phosphate group esterified to a glycerol molecule and an alcohol esterified to the phosphate group. All attachments (bonds) between groups in a glycerophospholipid are ester linkages, a situation similar to that in triacylglycerols (Section 19.4). However, glycerophospholipids have four ester linkages as contrasted to three ester linkages in triacylglycerols. Ester linkage

Ester linkage

G l y c e r o l

Fatty acid Ester linkage

Fatty acid Ester linkage

Phosphate Glycerophospholipid (four ester linkages)

Ester linkage

Alcohol

G l y c e r o l

Fatty acid Ester linkage

Fatty acid Ester linkage

Fatty acid Triacylglycerol (three ester linkages)

Because of the ester linkages present, glycerophospholipids undergo hydrolysis and saponification reactions in a manner similar to that for triacylglycerols (Section 19.6). There will be five reaction products, however, instead of the four for triacylglycerols.

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Phosphoric acid is the parent source for the minus one charged phosphate group used in the formation of glycerophospholipids. The structures of these two entities are O B HOO P O OH A OH

O B HOO P O OH A O⫺

Phosphoric acid

Minus one charged phosphate group

Phosphoric acid structures were previously considered in Section 16.20 when esters of inorganic acids were considered. The alcohol attached to the phosphate group in a glycophospholipid is usually one of three amino alcohols: choline, ethanolamine, or serine. The structures of these three amino alcohols, given in terms of the charged forms (Sections 17.8 and 20.4) that they adopt in neutral solution, are ⫹

⫹

⫹

HOOCH2 OCH2 O N(CH3 )3

HOOCH2 OCH2 O NH3

HOO CH2 O CHONH3 A COO⫺

Choline (a quaternary ammonium ion)

Ethanolamine (positive-ion form)

Serine (two ionic groups present)

Glycerophospholipids containing these three amino alcohols are respectively known as phosphatidylcholines, phosphatidylethanolamines, and phosphatidylserines. The fatty acid, glycerol, and phosphate portions of a glycerophospholipid structure constitute a phosphatidyl group.

EXAMPLE 19.5 Drawing the Structural Formula for a Glycerophospholipid

Draw the structural formula for the glycerophospholipid that produces, upon hydrolysis, equimolar amounts of glycerol, phosphoric acid, and ethanolamine, and twice that molar amount of stearic acid, the 18:0 fatty acid. Solution

The fact that the molar amount of stearic acid produced is twice that of the other products indicates that both fatty acid residues present in the glycerophospholipid are stearic acid residues. To draw the structural formula for this lipid, arrange the component parts in the following manner. Draw on the left the structure of glycerol, the “backbone” of the structure. Then place alongside it the two stearic acid and one phosphoric acid molecules. The acid placements should be such that their acid groups are lined up alongside the hydroxyl groups of glycerol. Then place the ion form of ethanolamine alongside the phosphoric acid molecule. O CH2 OH

HO

C O

CH

OH

HO

C O +

CH2 OH

HO

P

OH

HO

CH2 CH2 NH3

O–

The five components of the overall structure are then bonded together via ester linkages. The product of the formation of each ester linkage is a molecule of water. The atoms involved in this water formation are highlighted in color in the structures at the left and the ester linkages formed are highlighted in color in the structure at the right.

19.7 Membrane Lipids: Phospholipids

O CH2

OH

HO

O

C

CH2

O

O CH

OH

HO

OH

HO

C

P

C O

4H2O + CH

O

O CH2

631

C O

OH

HO

CH2

CH2

+

NH3

CH2

O

O–

P

O

CH2

CH2

+

NH3

O–

Practice Exercise 19.5 Draw the structure formula for the glycerophospholipid that produces, upon hydrolysis, equimolar amounts of glycerol, phosphoric acid, and choline, and twice that molar amount of lauric acid, the 12:0 fatty acid. O

Answer:

CH2 O

C O

CH

O

C O

CH2

O

P

O

CH2

CH2

+

N(CH3)3

O–

Glycerophospholipids have a hydrophobic (“water-hating”) portion, the nonpolar fatty acid groups, and a hydrophilic (“water-loving”) portion, the polar head group.

Although the general structural features of glycerophospholipids are similar in many respects to those of triacylglycerols, these two types of lipids have quite different biochemical functions. Triacylglycerols serve as storage molecules for metabolic fuel. Glycerophospholipids function almost exclusively as components of cell membranes (Section 19.10) and are not stored. A major structural difference between the two types of lipids, that of polarity, is related to their differing biochemical functions. Triacylglycerols are a nonpolar class of lipids, whereas glycerophospholipids are polar. In general, membrane lipids have polarity associated with their structures. Further consideration of general glycerophospholipid structure reveals an additional structural characteristic of most membrane lipids. Let us consider a phosphatidylcholine containing stearic and oleic acids to illustrate this additional feature. The chemical structure of this molecule is shown in Figure 19.13a. A molecular model for this compound, which gives the orientation of groups in space, is illustrated in Figure 19.13b. There are two important things to notice about this model: (1) There is a “head” part, the choline and phosphate, and (2) there are two “tails,” the two fatty acid carbon chains. The head part is polar. The two tails, the carbon chains, are nonpolar. All glycerophospholipids have structures similar to that shown in Figure 19.13. All have a “head” and two “tails.” A simplified representation for this structure uses a circle to represent the polar head and two wavy lines to represent the nonpolar tails. Polar head group

Nonpolar tails

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Chapter 19 Lipids

H

O

H C O

C

Head From two fatty acids

O H C O

H C O H

From glycerol

Tails

C

O

H

H

CH3

P O

C

C

N CH3

O–

H

H

CH3

+

From choline

Choline

Glycerol

Phosphate

From phosphate Hydrogen

Carbon

(a)

Cis double bond causes a bend. Oxygen

Phosphorus

Nitrogen

(b)

Figure 19.13 (a) Structural formula and (b) molecular model showing the “head and two tails” structure of a phosphatidylcholine molecule containing stearic acid (18:0) and oleic acid (18:1).

The amino alcohol in phosphatidylcholines (pronounced fahs-fuhTIDE-ul-KOH-leens) is choline.

The polar head group of a glycerophospholipid is soluble in water. The nonpolar tail chains are insoluble in water but soluble in nonpolar substances. This dual polarity, which we previously encountered when we discussed soaps (see the Chemical Connections feature on page 625), is a structural characteristic of most membrane lipids. Phosphatidylcholines are also known as lecithins. There are a number of different phosphatidylcholines because different fatty acids may be bonded to the glycerol portion of the phosphatidylcholine structure. In general, phosphatidylcholines are waxy solids that form colloidal suspensions in water. Egg yolks and soybeans are good dietary sources of these lipids. Within the body, phosphatidylcholines are prevalent in cell membranes. Periodically, claims arise that phosphatidylcholine should be taken as a nutritive supplement; some even maintain it will improve memory. There is no evidence that these supplements are useful. The enzyme lecithinase in the intestine hydrolyzes most of the phosphatidylcholine taken orally before it passes into body fluids, so it does not reach body tissues. The phosphatidylcholine present in cell membranes is made by the liver; thus phosphatidylcholines are not essential nutrients. The food industry uses phosphatidylcholines as emulsifiers to promote the mixing of otherwise immiscible materials. Mayonnaise, ice cream, and custards are some of the products they are found in. It is the polar–nonpolar (head–tail) structure of phosphatidylcholines that enables them to function as emulsifiers. Phosphatidylethanolamines and phosphatidylserines are also known as cephalins. These compounds are found in heart and liver tissue and in high concentrations in the brain. They are important in blood clotting. Much is yet to be learned about how these compounds function within the human body.

Sphingophospholipids Sphingophospholipids have structures based on the 18-carbon monounsaturated aminodialcohol sphingosine. A sphingophospholipid is a lipid that contains one fatty acid and one phosphate group attached to a sphingosine molecule and an alcohol attached to the phosphate group. The structure of sphingosine, the platform molecule for a sphingophospholipid, is When sphingolipids were discovered over a century ago by the physician– chemist Johann Thudichum (1829– 1901), their biochemical role seemed as enigmatic as the Sphinx, for which he named them.

CH3 O (CH2 )12 O CHPCHOCHO CHO CH2 A A A OH NH2 OH Sphingosine

All phospholipids derived from sphingosine have (1) the fatty acid attached to the sphingosine —NH2 group via an amide linkage, (2) the phosphate group attached to the sphingosine

19.7 Membrane Lipids: Phospholipids

633

Sphingosine

Fatty acid Polar head (b) A sphingophospholipid

(a) Sphingosine

Figure 19.14 Molecular models for (a) sphingosine and (b) a sphingophospholipid. The particular sphingophospholipid shown has choline as the alcohol esterified to the phosphate group. Note the “head and two tails” structure for the sphingophospholipid.

terminal —OH group via an ester linkage, and (3) an additional alcohol esterified to the phosphate group. The general block diagram for a sphingophospholipid is Sphingosine Amide linkage

Fatty acid Ester linkages

Phosphate

Alcohol

Sphingophospholipid (two ester linkages and one amide linkage)

In sphingophospholipids, the first three carbon atoms at the polar end of sphingosine are analogous to the three carbon atoms of glycerol in glycerophospholipids.

Molecular models showing orientation of atoms in space for sphingosine itself and for a sphingophospholipid are given in Figure 19.14. Note that, as in glycerophospholipids, the “head and two tails” structure is present in sphingophospholipids. For sphingophospholipids, the fatty acid is one of the tails, and the long carbon chain of sphingosine itself is the other tail. The polar head is the phosphate group with its esterified alcohol. Like glycerophospholipids, sphingophospholipids participate in saponification reactions. Amide linkages behave much as ester linkages do in this type of reaction. Sphingophospholipids in which the alcohol esterified to the phosphate group is choline are called sphingomyelins. Sphingomyelins are found in all cell membranes and are important structural components of the myelin sheath, the protective and insulating coating that surrounds nerves. The molecule depicted in Figure 19.14b is a sphingomyelin. The structural formula for a sphingomyelin in which stearic acid (18:0) is the fatty acid is Sphingosine HO

CH

CH

CH

(CH2)12

CH3

O CH

NH

C

(CH2)16

CH3

Stearic acid (18:0) O CH2

O

P

O

O– Phosphate

CH2

CH2

CH3 + N CH3 CH3

Choline

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Chapter 19 Lipids

19.8 MEMBRANE LIPIDS: SPHINGOGLYCOLIPIDS The second of the three major types of membrane lipids is sphingoglycolipids. A sphingoglycolipid is a lipid that contains both a fatty acid and a carbohydrate component attached to a sphingosine molecule. A fatty acid is attached to the sphingosine through an amide linkage, and a monosaccharide or oligosaccharide (Section 18.3) is attached to the sphingosine at the terminal —OH carbon atom through a glycosidic linkage (Section 18.13). The generalized block diagram for a sphingoglycolipid is Sphingosine Amide linkage

Fatty acid Glycosidic linkage

Monosaccharide or Oligosaccharide

Sphingoglycolipids undergo saponification reactions; both the amide and the glycosidic linkages can be hydrolyzed. The simplest sphingoglycolipids, which are called cerebrosides, contain a single monosaccharide unit—either glucose or galactose. As the name suggests, cerebrosides

Terminology for and Structural Relationships Among Various Types of Fatty-Acid-Containing Lipids ENERGY-STORAGE LIPIDS

MEMBRANE LIPIDS

Glycerol

Amino alcohol

Amino alcohol

Phosphate

Phosphate

Glycerol

Carbohydrate

Sphingosine

Sphingosine

Polar head group

Alcohol (platform molecule) Fatty acid chains

Triacylglycerol

Glycerophospholipid

Sphingophospholipid

Sphingoglycolipid

Phospholipids Glycerolipids

Sphingolipids

19.9 Membrane Lipids: Cholesterol

635

occur primarily in the brain (7% of dry mass). They are also present in the myelin sheath of nerves. The specific structure for a cerebroside in which stearic acid (18:0) is the fatty acid and galactose is the monosaccharide is Sphingosine

HO O CHO CHP CHO (CH2 )12 OCH3 A O A B A Stearic acid (18:0) CHONHO C O (CH2 )16 OCH3 A A A A O CH2 O O Galactose CH2 OH OH OH OH

More complex sphingoglycolipids, called gangliosides, contain a branched chain of up to seven monosaccharide residues. These substances occur in the gray matter of the brain as well as in the myelin sheath. The Chemistry at a Glance feature on page 634 summarizes terminology and structural relationships among the types of lipids that we have considered up to this point. The common thread among all of the structures is the presence of at least one fatty acid residue.

19.9 MEMBRANE LIPIDS: CHOLESTEROL Cholesterol, the third of the three major types of membrane lipids, is a specific compound rather than a family of compounds like the phospholipids (Section 19.7) and sphingoglycolipids (Section 19.8). Cholesterol’s structure differs markedly from that of other membrane lipids in that (1) there are no fatty acid residues present and (2) neither glycerol nor sphingosine is present as the platform molecule. Cholesterol is a steroid. A steroid is a lipid whose structure is based on a fusedring system that involves three 6-membered rings and one 5-membered ring. This steroid fused-ring system, which is called the steroid nucleus, has the following structure: 11

3

A 4

13

10 5

B 6

17

C 14 D 16 15

9

1 2

12

8 7

Steroid nucleus

B

F

Besides being an important molecule in and of itself, cholesterol serves as a precursor for several other important steroid molecules including bile acids (Section 19.11), steroid hormones (Section 19.12), and vitamin D (Section 21.13).

Note that each of the rings of the steroid nucleus carries a letter designation and that a “consecutive” numbering system is used to denote individual carbon atoms. Numerous steroids have been isolated from plants, animals, and human beings. Location of double bonds within the fused-ring system and the nature and location of substituents distinguish one steroid from another. Most steroids have an oxygen functional group (PO or —OH) at carbon 3 and some kind of side chain at carbon 17. Many also have a double bond from carbon 5 to either carbon 4 or carbon 6. Cholesterol is a C27 steroid molecule that is a component of cell membranes and a precursor for other steroid-based lipids. It is the most abundant steroid in the human body. The -ol ending in the name cholesterol conveys the information that an alcohol functional group is present in this molecule; it is located on carbon 3 of the steroid nucleus. In addition, cholesterol has methyl group attachments at carbons 10 and 13, a carbon–carbon double bond between carbons 5 and 6, and an eight-carbon branched side chain at carbon 17. Figure 19.15 gives both the structural formula and a molecular model

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Chapter 19 Lipids

Figure 19.15 Structural formula and molecular model for the cholesterol molecule.

CH3 CH

CH3

CH2 CH2 CH2 CH3 13

CH

CH3

17

CH3 10 3

HO

Figure 19.16 A severely occluded artery—the result of the buildup of cholesterol-containing plaque deposits.

for cholesterol. The molecular model shows the rather compact nature of the cholesterol molecule. The “head and two tails” arrangement found in other membrane lipids is not present. The lack of a large polar head group causes cholesterol to have limited water solubility. The —OH group on carbon 3 is considered the head of the molecule. Within the human body, cholesterol is found in cell membranes (up to 25% by mass), in nerve tissue, in brain tissue (about 10% by dry mass), and in virtually all fluids. Every 100 mL of human blood plasma contains about 50 mg of free cholesterol and about 170 mg of cholesterol esterified with various fatty acids. Although a portion of the body’s cholesterol is obtained from dietary intake, most of it is biosynthesized by the liver and (to a lesser extent) the intestine. Typically, 800–1000 mg are biosynthesized each day. Ingested cholesterol decreases biosynthetic cholesterol production. However, the reduction is less than the amount ingested. Therefore, total body cholesterol levels increase with increased dietary intake of cholesterol. Biosynthetic cholesterol is distributed to cells throughout the body for various uses via the bloodstream. Because cholesterol is only sparingly soluble in water (blood), a protein carrier system is used for its distribution. These cholesterol–protein combinations are called lipoproteins. The lipoproteins that carry cholesterol from the liver to various tissues are called LDLs (low-density lipoproteins), and those that carry excess cholesterol from tissues back to the liver are called HDLs (high-density lipoproteins). If too much cholesterol is being transported by LDLs or too little by HDLs, the imbalance results in an increase in blood cholesterol levels. High blood cholesterol levels contribute to atherosclerosis, a form of cardiovascular disease characterized by the buildup of plaque along the inner walls of arteries. Plaque is a mound of lipid material mixed with smooth muscle cells and calcium. Much of the lipid material in plaque is cholesterol. Plaque deposits in the arteries that serve the heart reduce blood flow to the heart muscle and can lead to a heart attack. Figure 19.16 shows the occlusion that can occur in an artery as a result of plaque buildup. The cholesterol associated with LDLs is often called “bad cholesterol” because it contributes to increased blood cholesterol levels, and the cholesterol associated with HDLs is often called “good cholesterol” because it contributes to reduced blood cholesterol levels. The Chemical Connections feature titled “Lipoproteins and Heart Disease Risk” on page 690 in the next chapter considers this topic in further detail. Much still needs to be learned concerning the actual role played by serum cholesterol in plaque buildup within arteries. Current knowledge suggests that it makes good sense to reduce the amount of cholesterol (as well as saturated fats) taken into the body through dietary intake. People who want to reduce dietary cholesterol intake should reduce the amount of animal products they eat (meat, dairy products, etc.) and eat more fruit and vegetables. Plant foods contain negligible amounts of cholesterol; cholesterol is found primarily in foods of animal origin. Table 19.4 gives cholesterol amounts associated with selected foods.

19.10 Cell Membranes

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TABLE 19.4 The Amount of Cholesterol Found in Various Foods

Food

Cholesterol (mg)

liver (3 oz) egg (1 large) shrimp (3 oz) pork chop (3 oz) chicken (3 oz) beef steak (3 oz) fish fillet (3 oz) whole milk (1 cup) cheddar cheese (1 oz) Swiss cheese (1 oz) low-fat milk (1 cup)

410 213 166 83 75 70 54 33 30 26 22

19.10 CELL MEMBRANES Cell membranes are also commonly called plasma membranes because they separate the cytoplasm (aqueous contents) of a cell from its surroundings. B

F

The percentage of lipid and protein components in a cell membrane is related to the function of the cell. The lipid/protein ratio ranges from about 80% lipid/20% protein by mass in the myelin sheath of nerve cells to the unique 20% lipid/80% protein ratio for the inner mitochondrial membrane (Section 23.2). Red blood cell membranes contain approximately equal amounts of lipid and protein. A typical membrane also has a carbohydrate content that varies between 2% and 10% by mass.

Prior to discussing additional types of lipid molecules—emulsification lipids (Section 19.11), messenger lipids (Sections 19.12 and 19.13), and protective-coating lipids (Section 19.14)— we will extend our discussion of membrane lipids to include how these types of lipids interact with each other to form cell membranes. Living cells contain an estimated 10,000 different kinds of molecules in an aqueous environment confined by a cell membrane. A cell membrane is a lipid-based structure that separates a cell’s aqueous-based interior from the aqueous environment surrounding the cell. Besides its “separation” function, a cell membrane also controls the movement of substances into and out of the cell. Up to 80% of the mass of a cell membrane is lipid material consisting primarily of the three types of membrane lipids we have just discussed: phospholipids, glycolipids, and cholesterol. The keys to understanding the structural basis for a cell membrane are (1) the virtually insoluble nature of membrane lipids in water and (2) the “head and two tails” structure (Section 19.7) of phospholipids and sphingoglycolipids. When these lipids are placed in water, the polar heads of phospholipids and sphingoglycolipids favor contact with water, whereas their nonpolar tails interact with one another rather than with water. The result is a remarkable bit of molecular architecture called a lipid bilayer. A lipid bilayer is a two-layer-thick structure of phospholipids and glycolipids in which the nonpolar tails of the lipids are in the middle of the structure and the polar heads are on the outside surfaces of the structure. Such a bilayer is six-billionths to nine-billionths of a meter thick—that is, 6 to 9 nanometers thick. There are three distinct parts to the bilayer: the exterior polar “heads,” the interior polar “heads,” and the central nonpolar “tails,” as shown in Figure 19.17.

Figure 19.17 Cross section of a lipid bilayer. The circles represent the polar heads of the lipid components, and the wavy lines represent the nonpolar tails of the lipid components. The heads occupy “surface” positions, and the tails occupy “internal” positions.

Inside of cell (aqueous solution) Interior polar heads Central nonpolar tails Exterior polar heads

Outside of cell (aqueous solution)

Cell membrane (lipid bilayer)

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Chapter 19 Lipids

Figure 19.18 Space-filling model of a section of a lipid bilayer. The key to the structure is the “head and two tails” structure of the membrane lipids that constitute the bilayer.

B

F

The glycerophospholipids and sphingoglycolipids found in a lipid bilayer are chiral molecules with the chiral center (Section 18.4) at carbon 2 of the glycerol or sphingosine components of the molecules. The stereoconfiguration of these chiral molecules is always “left-handed,” that is, L isomers. The fact that they all have the same configuration enhances their ability to aggregate together in the lipid bilayer.

Figure 19.19 The kinks associated with cis double bonds in fatty acid chains prevent tight packing of the lipid molecules in a lipid bilayer.

Figure 19.18, which is based on space-filling models for phospholipids, gives a “close-up” view of the arrangement of lipid molecules in a section of a lipid bilayer. Note the “exterior” nature of the polar heads of these membrane lipids. A lipid bilayer is held together by intermolecular interactions, not by covalent bonds. This means each phospholipid or sphingolipid is free to diffuse laterally within the lipid bilayer. Most lipid molecules in the bilayer contain at least one unsaturated fatty acid. The presence of such acids, with the kinks in their carbon chains (Section 19.3), prevents tight packing of fatty acid chains (Figure 19.19). The open packing imparts a liquidlike character to the membrane—a necessity because numerous types of biochemicals must pass into and out of a cell. Cholesterol molecules are also components of cell membranes. They regulate membrane fluidity. Because of their compact shape (Section 19.9; Figure 19.15), cholesterol molecules fit between the fatty acid chains of the lipid bilayer (Figure 19.20), restricting movement of the fatty acid chains. Within the membrane, the cholesterol molecule orientation is “head” to the outside (the hydroxyl group) and “tail” to the inside (the steroid ring structure with its attached alkyl groups). Proteins are also components of lipid bilayers. The proteins are responsible for moving substances such as nutrients and electrolytes across the membrane, and they also act as receptors that bind hormones and neurotransmitters. There are two general types of membrane proteins: integral and peripheral. An integral membrane protein is a membrane protein that penetrates the cell membrane. Some membrane proteins penetrate only partially through the lipid bilayer while others go completely from one side to the other side of the lipid bilayer. A peripheral membrane protein is a nonpenetrating membrane protein located on the surface of the cell membrane.

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19.10 Cell Membranes

Cholesterol

Figure 19.20 Cholesterol molecules fit between fatty acid chains in a lipid bilayer.

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Intermolecular forces rather than chemical bonds govern the interactions between membrane proteins and the lipid bilayer. Figure 19.21 shows diagrammatically the relationship between membrane proteins and the overall structure of a cell membrane. Small carbohydrate molecules are also components of cell membranes. They are found on the outer membrane surface covalently bonded to protein molecules (a glycoprotein) or lipid molecules (a glycolipid). The carbohydrate portions of glycoproteins and glycolipids function as markers, substances that play key roles in the process by which different cells recognize each other.

Transport Across Cell Membranes In order for cellular processes to be maintained, molecules of various types must be able to cross cell membranes. Three common transport mechanisms exist by which molecules can enter and leave cells. They are passive transport, facilitated transport, and active transport. Passive transport is the transport process in which a substance moves across a cell membrane by diffusion from a region of higher concentration to a region of lower concentration without the expenditure of any cellular energy. Only a few types of molecules, including O2, N2, H2O, urea, and ethanol, can cross membranes in this manner. Passive transport is closely related to the process of osmosis (Section 8.9). Facilitated transport is the transport process in which a substance moves across a cell membrane, with the aid of membrane proteins, from a region of higher concentration to a region of lower concentration without the expenditure of cellular energy. The specific protein molecules involved in the process are called carriers or transporters. A carrier protein forms a complex with a specific molecule at one surface of the membrane. Formation of the complex induces a conformational change in the protein that allows the molecule to move through a “gate” to the other side of the membrane. Once the molecule is released, the protein returns to its original conformation. Glucose, chloride ion, and bicarbonate ion cross membranes in this manner. Active transport is the transport process in which a substance moves across a cell membrane, with the aid of membrane proteins, against a concentration gradient with the expenditure of cellular energy. Proteins involved in active transport are called “pumps,” because they require energy much as a water pump requires energy in order to function. The needed energy is supplied by molecules such as ATP (Section 23.3). The need for energy expenditure is related to the molecules moving against a concentration gradient— from lower to higher concentration. It is essential to life processes to have some solutes “permanently” at different concentrations on the two sides of a membrane, a situation contrary to the natural tendency (osmosis) to establish equal concentrations on both sides Figure 19.21 Proteins are important Protein with carbohydrate marker

structural components of cell membranes.

Peripheral membrane protein

Outside of cell

Protein with carbohydrate marker

Lipid bilayer

Integral membrane proteins embedded in one side of the lipid bilayer Inside of cell

Integral membrane protein that extends across the lipid bilayer Cholesterol

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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Figure 19.22 Three processes by which substances can cross plasma membranes: (a) passive transport, (b) facilitated transport, and (c) active transport.

Gate

Pump

Concentration gradient: movement with the gradient; from high to low concentration Cellular energy expenditure: none required Protein help: none required

Concentration gradient: movement with the gradient; from high to low concentration Cellular energy expenditure: none required Protein help: proteins serve as “gates”

Concentration gradient: movement against the gradient; from low to high concentration Cellular energy expenditure: energy input required Protein help: proteins serve as “pumps”

(a) Passive Transport

(b) Facilitated Transport

(c) Active Transport

of a membrane. Hence the need for active transport. Sodium, potassium, and hydronium ions cross membranes through active transport. Figure 19.22 contrasts the processes of passive transport, facilitated transport, and active transport.

19.11 EMULSIFICATION LIPIDS: BILE ACIDS An emulsifier is a substance that can disperse and stabilize water-insoluble substances as colloidal particles in an aqueous solution. Cholesterol derivatives called bile acids function as emulsifying agents that facilitate the absorption of dietary lipids in the intestine. Their mode of action is much like that of soap during washing (see the Chemical Connections feature on page 625). A bile acid is a cholesterol derivative that functions as a lipid-emulsifying agent in the aqueous environment of the digestive tract. Approximately one-third of the daily production of cholesterol by the liver is converted to bile acids. Obtained by oxidation of cholesterol, bile acids differ structurally from cholesterol in three respects: 1. They are tri- or dihydroxy cholesterol derivatives. 2. The carbon 17 side chain of cholesterol has been oxidized to a carboxylic acid. 3. The oxidized acid side chain is bonded to an amino acid (either glycine or taurine) through an amide linkage. Figure 19.23 gives structural formulas for the three major types of bile acids produced from cholesterol by biochemical oxidation: cholic acid, 7-deoxycholic acid, and 12-deoxycholic Figure 19.23 Structural formulas for cholesterol, cholic acid, and two deoxycholic acids.

COO– HO 12

12

3

7

3

HO

7

OH

HO

Cholesterol (C27)

Cholic acid (C24) COO–

COO– HO

12

3

HO

12

7

3

OH

12-Deoxycholic acid (C24)

7

HO

7-Deoxycholic acid (C24)

19.12 Messenger Lipids: Steroid Hormones

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–

Figure 19.24 The structures of

COO OH CH3

glycocholic acid and taurocholic acid. CH3

OH

HO

Cholic acid +

H3N

CH2

CH2

+

–

SO3

H3N

Taurine

C HO CH3

O –

SO3

N H

N H

–

COO

CH3

OH

Taurocholic acid

The average bile acid composition in normal human adult bile is 38% cholic acid derivatives, 34% 7-deoxycholic acid derivatives, and 28% 12-deoxycholic acid derivatives. Glycine-containing derivatives predominate over taurine-containing derivatives by a 3:1 to 4:1 ratio. Uncomplexed (free) bile acids are not present in bile.

C HO CH3

CH3

Figure 19.25 A large percentage of gallstones, the causative agent for many “gallbladder attacks,” are almost pure crystallized cholesterol that has precipitated from bile solution.

–

COO

Glycine O

HO

CH2

HO

OH

Glycocholic acid

acid. The structural formulas are those for these bile acids prior to the attachment of the amino acid to the carbon 17 side chain. Bile acids always carry an amino acid (either glycine or taurine) attached to the side-chain carboxyl group via an amide linkage. The presence of this amino acid attachment increases both the polarity of the bile acid and its water solubility. Figure 19.24 shows the structures of glycocholic acid (glycine is the amino acid) and taurocholic acid (taurine is the amino acid). The medium through which bile acids are supplied to the small intestine is bile. Bile is a fluid containing emulsifying agents that is secreted by the liver, stored in the gallbladder, and released into the small intestine during digestion. Besides bile acids, bile also contains bile pigments (breakdown products of hemoglobin; Section 26.7), cholesterol itself, and electrolytes such as bicarbonate ion. The bile acids that are present increase the solubility of the cholesterol in the bile fluid. A number of factors, including increased secretion of cholesterol and a decrease in the size of the bile pool, can upset the balance between the cholesterol present in bile and the bile acid derivatives needed to maintain cholesterol’s solubility in the bile. The result is the precipitation of crystallized cholesterol from the bile and the resulting formation of gallstones in the gallbladder. In Western countries, approximately 80% of gallstones are almost pure cholesterol (see Figure 19.25).

19.12 MESSENGER LIPIDS: STEROID HORMONES We have previously considered lipids that function as energy-storage molecules (triacylglycerols; Section 19.4), as components of cell membranes (phospholipids, sphingoglycolipids, and cholesterol; Sections 19.7 through 19.9), and as emulsifying agents (bile acids; Section 19.11). An additional role played by lipids is that of “chemical messenger.” Steroid hormones and eicosanoids are two large families of lipids that have messenger functions. In this section we consider steroid hormones, which are cholesterol derivatives. In Section 19.13 we consider eicosanoids, which are fatty acid derivatives. A hormone is a biochemical substance, produced by a ductless gland, that has a messenger function. Hormones serve as a means of communication between various tissues. Some hormones, though not all, are lipids.

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A steroid hormone is a hormone that is a cholesterol derivative. There are two major classes of steroid hormones: (1) sex hormones, which control reproduction and secondary sex characteristics, and (2) adrenocorticoid hormones, which regulate numerous biochemical processes in the body.

Sex Hormones The sex hormones can be classified into three major groups: 1. Estrogens—the female sex hormones 2. Androgens—the male sex hormones 3. Progestins—the pregnancy hormones Estrogens are a class of molecules rather than a single molecule. Statements like “the estrogen level is high” should be rephrased as “there is a high level of estrogens.”

Figure 19.26 Structures of selected sex hormones and synthetic compounds that have similar actions.

Estrogens are synthesized in the ovaries and adrenal cortex and are responsible for the development of female secondary sex characteristics at the onset of puberty and for regulation of the menstrual cycle. They also stimulate the development of the mammary glands during pregnancy and induce estrus (heat) in animals. Androgens are synthesized in the testes and adrenal cortex and promote the development of secondary male characteristics. They also promote muscle growth. Progestins are synthesized in the ovaries and the placenta and prepare the lining of the uterus for implantation of the fertilized ovum. They also suppress ovulation. Figure 19.26a gives the structure of the primary hormone in each of the three subclasses of sex hormones. Other members of these hormone families are metabolized forms of the primary hormone. Note, in Figure 19.26a how similar the structures are for these principal hormones, and yet how different their functions. The fact that seemingly minor changes in structure effect great changes in biofunction points out, again, the extreme specificity (Section 21.5) of the enzymes that control biochemical reactions. Increased knowledge of the structures and functions of sex hormones has led to the development of a number of synthetic steroids whose actions often mimic those of the natural steroid hormones. The best known types of synthetic steroids are oral contraceptives and anabolic agents.

(a) NATURAL HORMONES O

CH3 OH

CH3 OH

CH3 C

H3C

CH3

H 3C

O

HO

O

Testosterone (the primary androgen; responsible for secondary male characteristics)

Estradiol (the primary estrogen; responsible for secondary female characteristics)

Progesterone (the primary progestin; prepares the uterus for pregnancy)

(b) SYNTHETIC STEROIDS CH3OH

(CH3) 2N C

CH

O

CH3OH

OH CH3 C

C

O

Norethynodrel (a synthetic progestin)

RU-486 (mifepristone; a synthetic abortion drug)

CH3

CH3

H 3C O

Methandrostenolone (a synthetic tissue-building steroid)

19.12 Messenger Lipids: Steroid Hormones

The CqC functional group, which occurs in both norethynodrel (Enovid) and RU-486, is rarely found in biomolecules.

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Oral contraceptives are used to suppress ovulation as a method of birth control. Generally, a mixture of a synthetic estrogen and a synthetic progestin is used. The synthetic estrogen regulates the menstrual cycle, and the synthetic progestin prevents ovulation, thus creating a false state of pregnancy. The structure of norethynodrel (Enovid), a synthetic progestin, is given in Figure 19.26b. Compare its structure to that of progesterone (the real hormone); the structures are very similar. Interestingly, the controversial “morning after” pill developed in France and known as RU-486, is also similar in structure to progesterone. RU-486 interferes with gestation of a fertilized egg and terminates a pregnancy within the first 9 weeks of gestation more effectively and safely than surgical methods. The structure of RU-486 appears next to that of norethynodrel in Figure 19.26b. Anabolic agents include the illegal steroid drugs used by some athletes to build up muscle strength and enhance endurance. Anabolic agents are now known to have serious side effects on the user. The Chemical Connections feature on page 644 focuses on the use of anabolic steroids. The structure of one of the more commonly used anabolic agents, methandrostenolone, is given in Figure 19.26b. Note the similarities between its structure and that of the naturally occurring testosterone.

Adrenocorticoid Hormones The second major group of steroid hormones consists of the adrenocorticoid hormones. Produced by the adrenal glands, small organs located on top of each kidney, at least 28 different hormones have been isolated from the adrenal cortex (the outer part of the glands). There are two types of adrenocorticoid hormones. 1. Mineralocorticoids control the balance of Na⫹ and K⫹ ions in cells and body fluids. 2. Glucocorticoids control glucose metabolism and counteract inflammation. The major mineralocorticoid is aldosterone, and the major glucocorticoid is cortisol (hydrocortisone). Cortisol is the hormone synthesized in the largest amount by the adrenal glands. Cortisol and its synthetic ketone derivative cortisone exert powerful anti-inflammatory effects in the body. Both cortisone and prednisolone, a similar synthetic derivative, are used as prescription drugs to control inflammatory diseases such as rheumatoid arthritis. Figure 19.27 gives the structures of these adrenocorticoid hormones.

Figure 19.27 Structures of selected adrenocorticoid hormones and related synthetic compounds.

(a) NATURAL HORMONES O HO

CH2OH

CH C

CH2OH

O HO

CH3

CH3C

O OH

CH3

O

O

Aldosterone (a mineralocorticoid)

Cortisol (a glucocorticoid)

(b) SYNTHETIC STEROIDS CH2OH O

CH C 3

CH2OH

O OH

HO

CH3 O

Cortisone (an anti-inflammatory drug)

CH3C

O OH

CH3 O

Prednisolone (an anti-inflammatory drug)

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19.13 MESSENGER LIPIDS: EICOSANOIDS

Eicosanoids exert their effects at very low concentrations, sometimes less than one part in a billion (109).

An eicosanoid is an oxygenated C20 fatty acid derivative that functions as a messenger lipid. The term eicosanoid is derived from the Greek word eikos, which means “twenty.” The metabolic precursor for most eicosanoids is arachidonic acid, the 20:4 fatty acid. Almost all cells, except red blood cells, produce eicosanoids. These substances, like hormones, have profound physiological effects at extremely low concentrations. Eicosanoids are hormonelike molecules rather than true hormones because they are not transported in the bloodstream to their site of action as true hormones are. Instead, they exert their effects in the tissues where they are synthesized. Eicosanoids usually have a very short “life,” being broken down, often within seconds of their synthesis, to inactive residues (which are eliminated in urine). For this reason, they are difficult to study and monitor within cells. The physiological effects of eicosanoids include mediation of 1. 2. 3. 4. 5. 6.

The inflammatory response, a normal response to tissue damage The production of pain and fever The regulation of blood pressure The induction of blood clotting The control of reproductive functions, such as induction of labor The regulation of the sleep/wake cycle

There are three principal types of eicosanoids: prostaglandins, thromboxanes, and leukotrienes.

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onnections

Steroid Drugs in Sports

The steroid hormone testosterone is the principal male sex hormone. It has masculinizing (androgenic) effects and musclebuilding (anabolic) effects. Masculinizing effects of testosterone include the growth of facial and body hair, deepening of the voice, and maturation of the male sex organs. Testosterone’s anabolic effects are responsible for the muscle development that boys experience at puberty. Some of the many synthetic testosterone derivatives exert primarily androgenic effects, whereas others exert primarily anabolic effects. Androgenic compounds can be used to correct hormonal imbalances in the body. Anabolic steroids can be used to prevent the withering of muscle in persons recovering from major surgery or serious injuries. Anabolic steroids have also been “discovered” by athletes, who have found that these compounds can be used to help build muscle mass and reduce the healing time for muscle injuries. Often the net result of anabolic hormone use by an athlete is enhanced athletic performance. The International Olympic Committee, as well as the NBA and NFL, prohibits steroid use and tests for it. Recently, major league baseball adopted a policy regarding the use of steroids. There are two reasons for steroid prohibition in athletics: (1) Their use is considered a form of cheating because it confers an unfair advantage, and (2) their “beneficial effects” are far outweighed by serious negative side effects.

Current medical evidence indicates that using anabolic steroids is dangerous. Steroid abuse is associated with a wide range of adverse side effects ranging from some that are physically unattractive, such as acne and breast development in men, to others that are life-threatening, such as heart attacks and liver problems. Most of these alarming effects are reversible if the abuser stops taking the drugs, but some are permanent. Steroid abuse disrupts the normal production of hormones in the body, causing both reversible and irreversible change. The male reproductive system is altered, causing testicular shrinkage and decreased sperm production. Both of these effects are reversible, but breast development is an irreversible change. In the female body, steroid abuse causes masculinization. Breast size and body fat decrease, the skin becomes coarse, and the voice deepens. Some women may experience excessive growth of body hair but lose hair from the scalp. A definite link exists between steroid abuse and cardiovascular diseases, including heart attacks and strokes, even in persons younger than 30. Steroids, particularly the oral types, increase the level of low-density lipoprotein (LDL) and decrease the level of high-density lipoprotein (HDL). High LDL and low HDL levels increase the risk of atherosclerosis. Steroids also increase the risk that blood clots will form in blood vessels.

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19.13 Messenger Lipids: Eicosanoids

Figure 19.28 Relationship of the structures of various eicosanoids to their precursor, arachidonic acid.

(b) PROSTAGLANDIN E2

(a) ARACHIDONIC ACID 9

8

6

5 4

7

3

2

COOH

11

18

16

13 12

14

17

15

20 19

13

OH

(d) LEUKOTRIENE B4

OH

OH 8

6

5

COOH

13 14

O

COOH

15

12

HO

(c) THROMBOXANE B2

HO

5

6

8

1

10

The capital letter–numerical subscript designations for individual eicosanoids is based on selected structural characteristics of the molecules. The numerical subscript indicates the number of carbon–carbon double bonds present. The letters denote subgroups of molecules. The prostaglandin E group, for example, has a carbonyl group on carbon 9.

O

12

12 15

OH 11

10

8 9

7

6

5

COOH

16

OH

Prostaglandins A prostaglandin is a messenger lipid that is a C20-fatty-acid derivative that contains a cyclopentane ring and oxygen-containing functional groups. Twenty-carbon fatty acids are converted into a prostaglandin structure when the eighth and twelfth carbon atoms of the fatty acid become connected to form a five-membered ring (Figure 19.28b). Prostaglandins are named after the prostate gland, which was first thought to be their only source. Today, more than 20 prostaglandins have been discovered in a variety of tissues in both males and females. Within the human body, prostaglandins are involved in many regulatory functions, including raising body temperature, inhibiting the secretion of gastric juices, increasing the secretion of a protective mucus layer into the stomach, relaxing and contracting smooth muscle, directing water and electrolyte balance, intensifying pain, and enhancing inflammation responses. Aspirin reduces inflammation and fever because it inactivates the enzyme needed for prostaglandin synthesis. Naturally occurring fatty acids are normally found in the form of fatty acid residues in such molecules as triacylglycerols, phospholipids, and sphingolipids, substances previously considered in this chapter. In eicosanoids the fatty acids are not esterified and carry out their biochemical roles in the form of the free acids, that is, free fatty acid derivatives.

Thromboxanes A thromboxane is a messenger lipid that is a C20-fatty-acid derivative that contains a cyclic ether ring and oxygen-containing functional groups. As with prostaglandins, the cyclic structure involves a bond between carbons 8 and 12 (Figure 19.28c). An important function of thromboxanes is to promote the formation of blood clots. Thromboxanes are produced by blood platelets and promote platelet aggregation.

Leukotrienes A leukotriene is a messenger lipid that is a C20-fatty-acid derivative that contains three conjugated double bonds and hydroxy groups. Fatty acids and their derivatives do not normally contain conjugated double bonds (see the Chemical Connections feature “Carotenoids: A Source of Color” on page 374 in Chapter 13), as is the case in leukotrienes (Figure 19.28d). Leukotrienes are found in leukocytes (white blood cells). Their source and the presence of the three conjugated double bonds account for their name. Various inflammatory and hypersensitivity (allergy) responses are associated with elevated levels of leukotrienes. The development of drugs that inhibit leukotriene synthesis has been an active area of research.

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The Mode of Action for Anti-Inflammatory Drugs

Injury or damage to bodily tissue is associated with the process of inflammation. This inflammation response is mediated by prostaglandin molecules (Section 19.13). The mode of action for most anti-inflammatory drugs now in use involves decreasing prostaglandin synthesis within the body by inhibiting the action of one or more of the enzymes (biochemical catalysts; Chapter 21) needed for prostaglandin synthesis. Prostaglandin molecules are derivatives of arachidonic acid, a 20:4 fatty acid (Section 19.13). Anti-inflammatory steroid drugs such as cortisone (Section 19.12) inhibit the action of the enzyme phospholipase A2, the enzyme that facilitates the breakdown of complex arachidonic acid-containing lipids to produce free arachidonic acid. Inhibiting arachidonic acid release stops the prostaglandin synthesis process, which in turn prevents (or diminishes) inflammation. Besides anti-inflammatory steroid drugs, many nonsteroidal anti-inflammatory drugs (NSAIDs) are also available for inflammation control. The most frequently used NSAIDs are the over-the-counter pain relievers aspirin, ibuprofen (Advil), and naproxen (Aleve). These substances, which have anti-pain, antifever, and anti-inflammatory properties, prevent prostaglandin synthesis by inhibiting the enzyme needed for the ring closure reaction at carbons 8 and 12 in arachidonic acid, a necessary step in prostaglandin synthesis (Section 19.13). The enzyme that NSAIDs inhibit is called cyclooxygenase, an enzyme known by the acronym COX. There are actually two forms of the COX enzyme: COX-1 and COX-2. The COX-1 enzyme is involved in the normal physiological production of prostaglandin molecules (a desirable situation) and the COX-2 enzyme is responsible for the prostaglandin production associated with the inflammation re-

sponse (a situation that is desirable to control). NSAIDs such as aspirin, ibuprofen, and naproxen inhibit both the COX-1 and COX-2 enzymes (the good and the bad). A new generation of prescription anti-inflammatory agents are now available that are COX-2 inhibitors but not COX-1 inhibitors. They have been touted by some as “super aspirins.” The best known of the COX-2 inhibitors are Vioxx and Celebrex, whose chemical structures are O

O O

H2N

O S N

H3C

N CF3

S O

O

H3C

Vioxx

Celebrex

Like almost all anti-inflammatory drugs, these drugs have ulcercausing side effects. In 2004, Vioxx was withdrawn from the market because of concerns relative to heart attacks and strokes. A study indicated that patients taking Vioxx were twice as likely to suffer a heart attack or stroke as a control group involved in the study who were taking a placebo. The actual risk was 3.5% in the Vioxx group, compared with 1.9% in the control group, according to the FDA. The difference became apparent after 18 months of Vioxx use. The use of COX-2 inhibitors is now a topic under intense scrunity.

19.14 PROTECTIVE-COATING LIPIDS: BIOLOGICAL WAXES A biological wax is a lipid that is a monoester of a long-chain fatty acid and a long-chain alcohol. Biological waxes are monoesters, unlike fats and oils (Section 19.4), which are triesters. The fatty acids found in biological waxes generally are saturated and contain from 14 to 36 carbon atoms. The alcohols found in biological waxes may be saturated or unsaturated and may contain from 16 to 30 carbon atoms. The block diagram for a biological wax is Long-chain fatty acid —— Long-chain alcohol

with the fatty acid and alcohol linked through an ester linkage. An actual structural formula for a biological wax that bees secrete and use as a structural material is The term wax derives from the old English word weax, which means “the material of the honeycomb.”

Fatty acid residue

Ester

O linkage B CH3 O (CH2 )14O C OOO (CH2 )29OCH3 A component of beeswax

Alcohol residue

19.14 Protective-Coating Lipids: Biological Waxes

Figure 19.29 A biological wax has a structure with a small, weakly polar “head” and two long, nonpolar “tails.” The polarity of the small “head” is not sufficient to impart any degree of water solubility to the molecule.

Stearic acid

647

O C

Oleoyl alcohol

O

(a)

(b)

Note that the general structural formula for a biological wax is the same as that for a simple ester (Section 16.10). O B ROCOOOR⬘

Figure 19.30 Plant leaves often have a biological wax coating to prevent excessive loss of water.

When aquatic birds are caught in an oil spill, the oil dissolves the wax coating on their feathers. This causes the birds to lose their buoyancy (they cannot swim properly) and compromises their protection against the effects of cold water.

However, for waxes both R and R⬘ must be long carbon chains (usually 20–30 carbon atoms). The water-insoluble, water-repellent properties of biological waxes result from the complete dominance of the nonpolar nature of the long hydrocarbon chains present (from the alcohol and the fatty acid) over the weakly polar nature of the ester functional group that links the two carbon chains together (see Figure 19.29). In living organisms biological waxes have numerous functions, all of which are related directly or indirectly to their water-repellent properties. Both humans and animals possess skin glands that secrete biological waxes to protect hair and skin and to keep it pliable and lubricated. With animal fur, waxes impart water repellency to the fur. Birds, particularly aquatic birds, rely on waxes secreted from preen glands to keep their feathers water repellent. Such wax coatings also help minimize loss of body heat when the bird is in cold water. Many plants, particularly those that grow in arid regions, have leaves that are coated with a thin layer of biological waxes, which serve to prevent excessive evaporation of water and to protect against parasite attack (see Figure 19.30). Similarly, insects with a high surface-area-to-volume ratio are often coated with a protective biological wax. Biological waxes find use in the pharmaceutical, cosmetics, and “polishing” industries. Carnauba wax (obtained from a species of Brazilian palm tree) is a particularly hard wax whose uses involve high-gloss finishes: automobile wax, boat wax, floor wax, and shoe wax. O B CH3 O (CH2 )28O C OOO (CH2 )31OCH3 A component of carnauba wax

Naturally occuring waxes, such as beeswax, are usually mixtures of several monoesters rather than being a single monoester. This parallels the situation for fats and oils, which are mixtures of numerous triesters (triacylglycerols).

Lanolin, a mixture of waxes obtained from sheep wool, is used as a base for skin creams and ointments intended to enhance retention of water (which softens the skin). Many synthetic materials are now available with properties that closely match—and even improve on—the properties of biological waxes. Such synthetic materials, which are generally polymers, have now replaced biological waxes in many cosmetics, ointments, and the like. The synthetic carbowax, for example, is a polyether. Throughout this discussion, we have used the term biological wax rather than just wax. This is because the everyday meaning of the term wax is broader in scope than the chemical definition of the term biological wax. In general discussions, a wax is a pliable, water-repelling substance used particularly in protecting surfaces and producing polished surfaces. This broadened definition for waxes includes not only biological waxes

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Types of Lipids in Terms of How They Function ENERGY-STORAGE LIPIDS Lipids stored for use when energy demand is high

Fats Triacylglycerols Oils Glycerophospholipids Phospholipids

MEMBRANE LIPIDS Lipids that are structural components of cell membranes

Lecithins Cephalins Sphingophospholipids

Cholesterol

Sphingomyelins Cerebrosides

Sphingoglycolipids Gangliosides EMULSIFICATION LIPIDS Lipids that stabilize and disperse water-insoluble materials in aqueous solution

Cholic acid Bile acids Deoxycholic acids Sex hormones Steroid hormones

MESSENGER LIPIDS

Estrogens Androgens Progestins Adrenocorticoids

Regulatory lipids that act in the tissue where they are synthesized or at other locations after transport via the bloodstream

Mineralocorticoids Glucocorticoids Prostaglandins Eicosanoids

Thromboxanes Leukotrienes

PROTECTIVE-COATING LIPIDS Water-insoluble, water-repellent lipids with protective-coating and lubricant functions

Human ear wax, which acts as a protective barrier against infection by capturing airborne particles, is not a true biological wax—that is, it is not a mixture of simple esters. Human ear wax is a yellow waxy secretion that is a mixture of triacylglycerols, phospholipids, and esters of cholesterol. Its medical name is cerumen.

Biological waxes

but also mineral waxes. A mineral wax is a mixture of long-chain alkanes obtained from the processing of petroleum. (How mineral waxes are obtained from petroleum was considered in Section 12.15.) Mineral waxes, which are also called paraffin waxes, resist moisture and chemicals and have no odor or taste. They serve as a waterproof coating for such paper products as milk cartons and waxed paper. Most candles are made from mineral waxes. Some “wax products” are a blend of biological and mineral waxes. For example, beeswax is sometimes a component of candle wax. The Chemistry at a Glance feature above summarizes the function-based lipid classifications we have considered in this chapter. Subclassifications within each function classification are also given in this summary.

Key Reactions and Equations

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Lipids. Lipids are a structurally heterogeneous group of compounds of biochemical origin that are soluble in nonpolar organic solvents and insoluble in water. Lipids are divided into five major types on the basis of biochemical function: energy-storage lipids, membrane lipids, emulsification lipids, messenger lipids, and protective-coating lipids (Section 19.1). Types of fatty acids. Fatty acids are monocarboxylic acids that contain long, unbranched carbon chains. The carbon chain may be saturated, monounsaturated, or polyunsaturated. Length of carbon chain, degree of unsaturation, and location of the unsaturation influence the properties of fatty acids. Omega-3 and omega-6 fatty acids are unsaturated fatty acids with the endmost double bond three and six carbons, respectively, away from the methyl end of the carbon chain (Section 19.2). Triacylglycerols. Triacylglycerols are energy-storage lipids formed by esterification of three fatty acids to a glycerol molecule. Fats are triacylglycerol mixtures that are solids or semi-solids at room temperature; they contain a relatively high percentage of saturated fatty acid residues. Oils are triacylglycerol mixtures that are liquids at room temperature; they contain a relatively high percentage of unsaturated fatty acid residues (Section 19.4). Phospholipids. Phospholipids are membrane lipids that contain one or more fatty acids, a phosphate group, a platform molecule to which the fatty acid(s) and phosphate group are attached, and an alcohol attached to the phosphate group. The platform molecule is either glycerol (glycerophospholipids) or sphingosine (sphingophospholipids). Phospholipids have a “head and two tails” structure. Lecithins, cephalins, and sphingomyelins are types of phospholipids (Section 19.7). Sphingoglycolipids. Sphingoglycolipids are membrane lipids in which a fatty acid and a mono- or oligosaccharide are attached to the platform molecule sphingosine. Cerebrosides and gangliosides are types of sphingoglycolipids (Section 19.8).

k

Cholesterol. Cholesterol is a membrane lipid whose structure con-

tains a steroid nucleus. It is the most abundant type of steroid. Besides its membrane functions, it also serves as a precursor for several other types of lipids (Section 19.9). Lipid bilayer. A lipid bilayer is the fundamental structure associated with a cell membrane. It is a two-layer structure of lipid molecules (mostly phospholipids and glycolipids) in which the nonpolar tails of the lipids are in the interior and the polar heads are on the outside surfaces (Section 19.10). Membrane transport mechanisms. The transport mechanisms by which molecules enter and leave cells include passive transport, facilitated transport, and active transport. Passive and facilitated transport follow a concentration gradient and do not involve cellular energy expenditure. Active transport involves movement against a concentration gradient and requires the expenditure of cellular energy (Section 19.10). Bile acids. Bile acids are cholesterol derivatives that function as emsulsification lipids. They cause dietary lipids to be soluble in the aqueous environment of the digestive tract. Cholic acid and deoxycholic acids are the major types of bile acids (Section 19.11). Steroid hormones. Steroid hormones are cholesterol derivatives that function as messenger lipids. The two major types of steroid hormones are sex hormones and adrenocorticoid hormones (Section 19.12). Eicosanoids. Eicosanoids are fatty acid derivatives that function as messenger lipids. The major classes of eicosanoids are prostaglandins, thromboxanes, and leukotrienes (Section 19.13). Biological waxes. Biological waxes are protective-coating lipids formed through the esterification of a long-chain fatty acid to a longchain alcohol (Section 19.14).

EY R E A C T I O N S A N D E Q U AT I O N S 3. Saponification of a triacylglycerol to produce glycerol and fatty acid salts (Section 19.6)

1. Formation of a triacylglycerol (Section 19.6)

Glycerol + 3 fatty acids

Enzymes

G l y c e r o l

Fatty acid Fatty acid

+ 3H2O

Fatty acid

2. Hydrolysis of a triacylglycerol to produce glycerol and fatty acids (Section 19.6) G l y c e r o l

649

Fatty acid Fatty acid Fatty acid

+ 3H2O

H+ or enzymes

Glycerol + 3 fatty acids

G l y c e r o l

Fatty acid Fatty acid

+ 3OH

–

Glycerol + 3 fatty acid salts

Fatty acid

4. Hydrogenation of a triacylglycerol to reduce the unsaturation of its fatty acid components (Section 19.6) G l y c e r o l

Monounsaturated fatty acid Saturated fatty acid Monounsaturated fatty acid

+ 2H2

G l y c e r o l

Saturated fatty acid Saturated fatty acid Saturated fatty acid

650

Chapter 19 Lipids

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Structure and Classification of Lipids (Section 19.1) 19.1 What characteristic do all lipids have in common? 19.2 What structural feature, if any, do all lipid molecules have in common? Explain your answer. 19.3 Would you expect lipids to be soluble or insoluble in each of

the following solvents? a. H2O (polar) b. CH3—CH2—O—CH2—CH3 (nonpolar) c. CH3—OH (polar) d. CH3—CH2—CH2—CH2—CH3 (nonpolar) 19.4 Would you expect lipids to be soluble or insoluble in each of the following solvents? a. CH3—(CH2)7—CH3 (nonpolar) b. CH3—Cl (polar) c. CCl4 (nonpolar) d. CH3—CH2—OH (polar) 19.5 In terms of biochemical function, what are the five major

categories of lipids? 19.6 What is the biochemical function of each of the following types of lipids? a. Triacylglycerols b. Bile acids c. Sphingoglycolipids d. Eicosanoids Types of Fatty Acids (Section 19.2) 19.7 Classify each of the following fatty acids as long-chain, medium-chain, or short-chain. a. Myristic (14:0) b. Caproic (6:0) c. Arachidic (20:0) d. Capric (10:0) 19.8 Classify each of the following fatty acids as long-chain, medium-chain, or short-chain. a. Lauric (12:0) b. Oleic (18:1) c. Butyric (4:0) d. Stearic (18:0) 19.9 Classify each of the following fatty acids as saturated, mono-

unsaturated, or polyunsaturated. a. Stearic (18:0) b. Linolenic (18:3) c. Docosahexaenoic (22:6) d. Oleic (18:1) 19.10 Classify each of the following fatty acids as saturated, monounsaturated, or polyunsaturated. a. Palmitic (16:0) b. Linoleic (18:2) c. Arachidonic (20:4) d. Palmitoleic (16:1) 19.11 Structurally, what is the difference between a SFA and a

MUFA?

19.12 Structurally, what is the difference between a MUFA and a

PUFA?

19.13 With the help of Table 19.1, classify each of the acids in

Problem 19.9 as an omega-3 acid, an omega-6 acid, or neither an omega-3 nor an omega-6 acid. 19.14 With the help of Table 19.1, classify each of the acids in Problem 19.10 as an omega-3 acid, an omega-6 acid, or neither an omega-3 nor an omega-6 acid. 19.15 Draw the condensed structural formula for the fatty acid whose

numerical shorthand designation is 18:2 (⌬9,12). 19.16 Draw the condensed structural formula for the fatty acid whose numerical shorthand designation is 20:4 (⌬5,8,11,14).

19.17 Using the structural information given in Table 19.1, assign an

IUPAC name to each of the following fatty acids. a. Myristic acid b. Palmitoleic acid 19.18 Using the structural information given in Table 19.1, assign an IUPAC name to each of the following fatty acids. a. Stearic acid b. Linolenic acid Physical Properties of Fatty Acids (Section 19.3) 19.19 What is the relationship between carbon chain length and melting point for fatty acids? 19.20 What is the relationship between degree of unsaturation and melting point for fatty acids? 19.21 Why does the introduction of a cis double bond into a fatty acid

lower its melting point?

19.22 Why does increasing carbon chain length decrease water solu-

bility for fatty acids?

19.23 In each of the following pairs of fatty acids, select the fatty acid

that has the lower melting point. a. 18:0 acid and 18:1 acid b. 18:2 acid and 18:3 acid c. 14:0 acid and 16:0 acid d. 18:1 acid and 20:0 acid 19.24 In each of the following pairs of fatty acids, select the fatty acid that has the higher melting point. a. 14:0 acid and 18:0 acid b. 20:4 acid and 20:5 acid c. 18:3 acid and 20:3 acid d. 16:0 acid and 16:1 acid Triacylglycerols (Section 19.4) 19.25 What are the four structural subunits that contribute to the structure of a triacylglycerol? 19.26 Draw the general block diagram for a triacylglycerol. 19.27 How many different kinds of functional groups are present in a

triacylglycerol in which all three fatty acid residues come from saturated fatty acids? 19.28 How many different kinds of functional groups are present in a triacylglycerol in which all three fatty acid residues come from unsaturated fatty acids? 19.29 Draw the condensed structural formula of a triacylglycerol

formed from glycerol and three molecules of palmitic acid. 19.30 Draw the condensed structural formula of a triacylglycerol formed from glycerol and three molecules of stearic acid. 19.31 Draw block diagram structures for the four different triacyl-

glycerols that can be produced from glycerol, stearic acid, and linolenic acid. 19.32 Draw block diagram structures for the three different triacylglycerols that can be produced from glycerol, palmitic acid, stearic acid, and linolenic acid. 19.33 Identify the fatty acids present in each of the following

triacylglycerols. a. O B CH2 OOOCO (CH2 )14 O CH3 A O A B A CHOOO CO(CH2 )12 O CH3 A O A B A CH2 OOOCO(CH2 )7 O CHP CHO (CH2 )7 OCH3

Exercises and Problems

b.

O B CH2 OOOC A O A B A CHOOO C A O A B A CH2 OOOC

19.34 Identify the fatty acids present in each of the following

triacylglycerols.

a.

O B CH2 OOOC O (CH2 )16 OCH3 A O A B A CHOOOC O(CH2 )7 O CHPCHO (CH2 )7 OCH3 A O A B A CH2 OOOC O(CH2 )12 OCH3 b. O B CH2 OOOC A O A B A CHOOO C A O A B A CH2 OOOC 19.35 For each of the acyl groups present in the triacylglycerol of

Problem 19.33a, indicate how many carbon atoms are present and how many oxygen atoms are present. 19.36 For each of the acyl groups present in the triacylglycerol of Problem 19.34a, indicate how many carbon atoms are present and how many oxygen atoms are present. 19.37 What is the difference in meaning, if any, between the members

of each of the following pairs of terms? a. Triacylglycerol and triglyceride b. Triacylglycerol and fat c. Triacylglycerol and mixed triacylglycerol d. Fat and oil 19.38 What is the difference in meaning, if any, between the members of each of the following pairs of terms? a. Triacylglycerol and oil b. Triacylglycerol and simple triacylglycerol c. Simple triacylglycerol and mixed triacylglycerol d. Triglyceride and fat Dietary Considerations and Triacylglycerols (Section 19.5) 19.39 In a dietary context, indicate whether each of the following pairings of concepts is correct. a. “Saturated fat” and “good fat” b. “Polyunsaturated fat” and “bad fat” 19.40 In a dietary context, indicate whether each of the following pairings of concepts is correct. a. “Monounsaturated fat” and “good fat” b. “Saturated fat” and “good and bad fat” 19.41 In a dietary context, which of the following pairings of concepts

is correct? a. “Cold-water fish” and “high in omega-3 fatty acids” b. “Fatty fish” and “low in omega-3 fatty acids”

651

19.42 In a dietary context, which of the following pairings of concepts

is correct? a. “Warm-water fish” and “low in omega-3 fatty acids” b. “Fish and chips” and “high in omega-3 fatty acids”

19.43 In a dietary context, classify each of the following fatty acids as

an essential fatty acid or as a nonessential fatty acid. a. Lauric acid (12:0) b. Linoleic acid (18:2) c. Myristic acid (14:0) d. Palmitoleic (16:1) 19.44 In a dietary context, classify each of the following fatty acids as an essential fatty acid or as a nonessential fatty acid. a. Stearic acid (18:0) b. Linolenic acid (18:3) c. Oleic acid (18:1) d. Arachidic acid (20:0) Chemical Reactions of Triacylglycerols (Section 19.6) 19.45 Name, in general terms, the organic products of the complete

a. hydrolysis of a fat b. saponification of an oil 19.46 Name, in general terms, the organic products of the complete a. saponification of a fat b. hydrolysis of an oil 19.47 Draw condensed structural formulas for all products you

would obtain from the complete hydrolysis of the following triacylglycerol.

O B CH2 OOOCO (CH2 )14 O CH3 A O A B A CHOOO CO(CH2 )12 O CH3 A O A B A CH2 OOOCO(CH2 )7 O CHP CHO (CH2 )7 OCH3 19.48 Draw condensed structural formulas for all products you

would obtain from the complete hydrolysis of the following triacylglycerol.

O B CH2 OOOCO (CH2 )16 OCH3 A O A B A CHOOO CO(CH2 )12 O CH3 A O A B A CH2 OOOCO(CH2 )6 O (CH2 OCHP CH)3 O CH2 OCH3 19.49 With the help of Table 19.1, determine the names of each of the

organic products obtained in Problem 19.47.

19.50 With the help of Table 19.1, determine the names of each of the

organic products obtained in Problem 19.48.

19.51 Draw condensed structural formulas for all products you would

obtain from the saponification with NaOH of the triacylglycerol in Problem 19.47. 19.52 Draw condensed structural formulas for all products you would obtain from the saponification with KOH of the triacylglycerol in Problem 19.48. 19.53 With the help of Table 19.1, name each of the products obtained

in Problem 19.51.

652

Chapter 19 Lipids

19.54 With the help of Table 19.1, name each of the products obtained

in Problem 19.52.

19.55 Why can only unsaturated triacylglycerols undergo

hydrogenation? 19.56 A food package label lists an oil as “partially hydrogenated.” What does this mean? 19.57 How many molecules of H2 will react with one molecule of the

following triacylglycerol?

O B CH2 OOOC O(CH2 )6 O (CH2 O CHP CH)2 O(CH2 )4 O CH3 A O A B A CHOOO CO(CH2 )7 O CHP CHO(CH2 )7 OCH3 A O A B A CH2 OOOC O(CH2 )6 O(CH2 O CHP CH)3 O CH2 OCH3 19.58 How many molecules of H2 will react with one molecule of the

following triacylglycerol?

O B CH2 OOOCO(CH2 )7 OCHP CHO(CH2 )7 OCH3 A O A B A CHOOO CO (CH2 )16 OCH3 A O A B A CH2 OOOCO(CH2 )6 O(CH2 OCHP CH)3 O CH2 OCH3 19.59 Draw block diagram structures for all possible products of the

partial hydrogenation, with two molecules of H2, of the following molecules. a. G b. G 18:1 Fatty acid 18:0 Fatty acid l l y y c c 18:1 Fatty acid 18:2 Fatty acid e e r r o o 16:1 Fatty acid 16:1 Fatty acid l l

19.60 Draw block diagram structures for all possible products of the

partial hydrogenation, with two molecules of H2, of the following molecules. a. G b. G l X 20:1 Fatty acid l X 20:1 Fatty acid y y c c e X 18:1 Fatty acid e X 18:0 Fatty acid r r o X 18:1 Fatty acid o X 18:2 Fatty acid l l

19.65 Draw the general block diagram for a glycerophospholipid. 19.66 Draw the general block diagram for a sphingophospholipid. 19.67 Draw the structures of the three amino alcohols commonly

esterified to the phosphate group in a glycerophospholipid.

19.68 What structural subunits are present in a phosphatidyl group? 19.69 Sphingophospholipids have a “head and two tails” structure.

Give the chemical identity of the head and of each of the two tails. 19.70 Glycerophospholipids have a “head and two tails” structure. Give the chemical identity of the head and of each of the two tails. 19.71 Which portion of the structure of a phospholipid has

hydrophobic characteristics?

19.72 Which portion of the structure of a phospholipid has

hydrophilic characteristics?

19.73 Indicate how many ester linkages are present in the structure of a

a. glycerophospholipid b. sphingophospholipid 19.74 Indicate how many amide linkages are present in the structure of a a. glycerophospholipid b. sphingophospholipid 19.75 Structurally, what is the difference between a lecithin and a

phosphatidylserine?

19.76 Structurally, what is the difference between a lecithin and a

sphingomyelin?

Sphingoglycolipids (Section 19.8) 19.77 Draw the general block diagram for a sphingoglycolipid. 19.78 How many of each of the following types of linkages are

present in a sphingoglycolipid? a. Ester linkages b. Amide linkages c. Glycosidic linkages

19.79 How does the general structure of a sphingoglycolipid differ

from that of a sphingophospholipid? 19.80 Structurally, what is the difference between a cerebroside and a ganglioside? Cholesterol (Section 19.9) 19.81 Draw and number the fused hydrocarbon ring system characteristic of all steroids. 19.82 What positions in the steroid nucleus are particularly likely to bear substituents? 19.83 Describe the structure of cholesterol in terms of substituents

attached to the steroid nucleus.

19.84 Structurally, what is considered the “head” of a cholesterol

molecule?

19.85 In a dietary context, what is the difference between “good

cholesterol” and “bad cholesterol”?

19.86 In a dietary context, how do HDL and LDL differ in function?

19.61 Why do animal fats and vegetable oils become rancid when

Cell Membranes (Section 19.10) 19.87 What are the three major types of lipids present in cell membranes? 19.88 What is the structural characteristic common to all the nonsteroid lipids present in cell membranes?

Phospholipids (Section 19.7) 19.63 What are the two common types of platform molecules for a phospholipid? 19.64 How many fatty acid residues are present in a phospholipid?

19.89 What is a lipid bilayer?

exposed to moist, warm air? 19.62 Why are the compounds BHA and BHT often added to foods that contain fats and oils?

19.90 What is the basic structure of a cell membrane? 19.91 What is the function of unsaturation in the hydrocarbon tails of

membrane lipids?

Additional Problems

19.92 What function does cholesterol serve when it is present in cell

membranes?

19.93 What is an integral membrane protein? 19.94 What is a peripheral membrane protein? 19.95 What is the difference between passive transport and facilitated

653

Steroid Hormones (Section 19.12) 19.109 What are the two major classes of steroid hormones? 19.110 Describe the general function of each of the following types of

steroid hormones. a. Estrogens c. Progestins

b. Androgens d. Mineralocorticoids

transport? 19.96 What is the difference between facilitated transport and active transport?

19.111 How do the sex hormones estradiol and testosterone differ in

19.97 Match each of the following statements related to membrane

19.112 What functional groups are present in each of the following

transport processes to the appropriate term: passive transport, facilitated transport, active transport. More than one term may apply in a given situation. a. Movement across the membrane is against the concentration gradient. b. Proteins serve as “gates.” c. Expenditure of cellular energy is required. d. Movement across the membrane is from a high to a low concentration. 19.98 Match each of the following statements related to membrane transport processes to the appropriate term: passive transport, facilitated transport, active transport. More than one term may apply in a given situation. a. Movement across the membrane is with the concentration gradient. b. Proteins serve as “pumps.” c. Expenditure of cellular energy is not required. d. Movement across the membrane is from a low to a high concentration. Bile Acids (Section 19.11) 19.99 What is an emulsifier? 19.100 How do bile acids aid in the digestion of lipids? 19.101 Describe the structural differences between a bile acid and

cholesterol.

19.102 Describe the structural differences between cholic acid and a

deoxycholic acid.

19.103 Describe the structural differences between glycocholic acid

and taurocholic acid. 19.104 Describe the structural differences between glycocholic acid and glyco-7-deoxycholic acid. 19.105 What is the medium through which bile acids are supplied to

the small intestine? 19.106 What is the chemical composition of bile?

19.107 At what location in the body are bile acids stored until

needed? 19.108 What is the chemical composition of the majority of gallstones?

structure?

steroid hormones or synthetic steroids? a. Estradiol b. Testosterone c. Progesterone d. Cortisone

19.113 Indicate whether or not each of the following is an adrenal

corticoid hormone or a sex hormone. a. Aldosterone b. Testosterone c. Cortisol d. Estradiol 19.114 Indicate whether each of the following is a natural steroid hormone or a synthetic steroid. a. Cortisone b. Progesterone c. Prednisolone d. Norethynodrel

19.115 What is the biochemical function for each of the steroids listed

in Problem 19.113?

19.116 What is the biochemical function for each of the steroids listed

in Problem 19.114?

Eicosanoids (Section 19.13) 19.117 What is the major structural difference between a prostaglan-

din and its parent fatty acid?

19.118 What is the major structural difference between a leukotriene

and its parent fatty acid?

19.119 What structural feature distinguishes a prostaglandin from a

leukotriene?

19.120 What structural feature distinguishes a thromboxane from a

leukotriene?

19.121 List six physiological processes that are regulated by eicosanoids. 19.122 What is the biochemical basis for the effectiveness of aspirin

in decreasing inflammation?

Biological Waxes (Section 19.14) 19.123 Draw the general block diagram for a biological wax. 19.124 Draw the condensed structural formula of a wax formed

from palmitic acid (Table 19.1) and cetyl alcohol, CH3—(CH2)14—CH2—OH.

19.125 What is the difference between a biological wax and a mineral

wax?

19.126 Biological waxes have a “head and two tails” structure. Give

the chemical identity of the head and of the two tails.

A DD D ITIO NA L P R O BL L EMS 19.127 Classify each of the following types of lipids as (1) glycerol-

based, (2) sphingosine-based, or (3) neither glycerol-based nor sphingosine-based. a. Bile acids b. Fats c. Waxes d. Leukotrienes 19.128 Indicate whether each of the lipid types in Problem 19.127 has a “head and two tails” structure.

19.129 Identify the type of lipid that fits each of the following

“structural component” characterizations. a. Sphingosine ⫹ fatty acid ⫹ phosphoric acid ⫹ choline b. Fused-ring system with three 6-membered rings and one 5-membered ring c. 20-carbon fatty acid ⫹ cyclopentane ring d. Sphingosine ⫹ fatty acid ⫹ monosaccharide

654

Chapter 19 Lipids

19.130 Classify each of the following types of lipids as (1) an energy-

storage lipid, (2) a membrane lipid, (3) an emulsification lipid, (4) a messenger lipid, or (5) a protective-coating lipid. a. Fats b. Estrogens c. Sphingomyelins d. Prostaglandins 19.131 Which of the terms glycerolipid, sphingolipid, and phospholipid apply to each of the following lipids? More than one term may apply in a given situation. a. Triacylglycerol b. Sphingoglycolipid c. Glycerophospholipid d. Sphingophospholipid

19.132 Specify the numbers of ester linkages, amide linkages, and gly-

cosidic linkages present in each of the following types of lipids. a. Oils b. Sphinogomyelins c. Cerebrosides d. Phosphatidylcholines 19.133 Indicate whether each of the following types of lipids contain a “steroid nucleus” as part of its structure. a. Prostaglandins b. Cortisone c. Bile acids d. Leukotrienes

multiple-Choice Practice Test 19.134 Which of the following statements concerning fatty acids is

19.135

19.136

19.137

19.138

correct? a. They are naturally occurring dicarboxylic acids. b. They are rarely found in the free state in nature. c. Their carbon chains always contain at least two double bonds. d. They almost always contain an odd number of carbon atoms. Which of the following is a distinguishing characteristic between fats and oils? a. Physical state at room temperature b. Identity of the alcohol component present c. Number of structural subunits present d. Number of fatty acid residues present Partial hydrogenation of a fat or an oil does which of the following? a. Produces fatty acid salts b. Decreases the degree of fatty acid unsaturation c. Decreases the melting point d. Increases the number of fatty acid residues present In the oxidation of fats and oils, which part of the molecule is attacked by the oxidizing agent? a. Carbon–carbon double bonds b. Ester linkages c. Hydroxyl groups d. Carboxyl groups In which of the following pairs of lipids are both members of the pair membrane lipids? a. Triacylglycerols and cholesterol b. Triacylglycerols and sphingophospholipids c. Sphingophospholipids and sphingoglycolipids d. Eicosanoids and bile salts

19.139 Which of the following types of lipids does not have a “head

19.140

19.141

19.142

19.143

and two tails” structure? a. Glycerophospholipids b. Sphingophospholipids c. Sphingoglycolipids d. Triacylglycerols The “steroid nucleus” of steroid lipids involves a fused-ring system that has how many rings? a. Two b. Three c. Four d. Five Which of the following polarity-based descriptions is correct for a lipid bilayer? a. Both the outer and inner surfaces contain polar “heads.” b. Both the outer and inner surfaces contain nonpolar “heads.” c. Both the outer and the inner surfaces contain polar “tails.” d. Both the outer and the inner surfaces contain nonpolar “tails.” Based on function, eicosanoids are classified as which of the following? a. Membrane lipids b. Emulsification lipids c. Messenger lipids d. Protective-coating lipids How many structural subunits are present in the “block diagram” for a biological wax? a. Two b. Three c. Four d. Five

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20

Proteins Chapter Outline 20.1

Characteristics of Proteins 655

20.2 Amino Acids: The Building Blocks for Proteins 656 20.3 Chirality and Amino Acids 658 20.4 Acid–Base Properties of Amino Acids 659 20.5 Cysteine: A Chemically Unique Amino Acid 663 20.6 Peptides 663 20.7 Biochemically Important Small Peptides 667 20.8 General Structural Characteristics of Proteins 668 20.9 Primary Structure of Proteins 670 20.10 Secondary Structure of Proteins 671 20.11 Tertiary Structure of Proteins 674 20.12 Quaternary Structure of Proteins 677 20.13 Protein Classification Based on Shape 679 20.14 Protein Classification Based on Function 682

CHEMISTRY AT A GLANCE: Protein Structure 678 20.15 Protein Hydrolysis 683 20.16 Protein Denaturation 684 20.17 Glycoproteins 685 20.18 Lipoproteins 689

The fibrous protein alpha-keratin is the major structural element present in sheep's wool.

I

n this chapter we consider the third of the bioorganic classes of molecules (Section 18.1), the compounds called proteins. An extraordinary number of different proteins, each with a different function, exist in the human body. A typical human cell contains about 9000 different kinds of proteins, and the human body contains about 100,000 different proteins. Proteins are needed for the synthesis of enzymes, certain hormones, and some blood components; for the maintenance and repair of existing tissues; for the synthesis of new tissue; and sometimes for energy.

CHEMICAL CONNECTIONS The Essential Amino Acids 658 Substitutes for Human Insulin 671 Protein Structure and the Color of Meat 682 Denaturation and Human Hair 686 Cyclosporine: An Antirejection Drug 688 Lipoproteins and Heart Disease Risk 690

20.1 CHARACTERISTICS OF PROTEINS Next to water, proteins are the most abundant substances in nearly all cells — they account for about 15% of a cell’s overall mass (Section 18.1) and for almost half of a cell’s dry mass. All proteins contain the elements carbon, hydrogen, oxygen, and nitrogen; most also contain sulfur. The presence of nitrogen in proteins sets them apart from carbohydrates and lipids, which most often do not contain nitrogen. The average nitrogen content of proteins is 15.4% by mass. Other elements, such as phosphorus and iron, are essential constituents of certain specialized proteins. Casein, the main protein of milk, contains phosphorus, an element very important in the diet of infants and children. Hemoglobin, the oxygen-transporting protein of blood, contains iron. A protein is a naturally occurring, unbranched polymer in which the monomer units are amino acids. Thus the starting point for a discussion of proteins is an understanding of the structures and chemical properties of amino acids.

655 Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

656

Chapter 20 Proteins

The word protein comes from the Greek proteios, which means “of first importance.” This reflects the key role that proteins play in life processes.

In an a-amino acid, the carboxyl group and the amino group are attached to the same carbon atom. The nature of the side chain (R group) distinguishes -amino acids from each other, both physically and chemically.

The nonpolar amino acid proline has a structural feature not found in any other standard amino acid. Its side chain, a propyl group, is bonded to both the a-carbon atom and the amino nitrogen atom, giving a cyclic side chain. H2C HN

CH2 CH2 C COOH H Proline

B

F

A variety of functional groups are present in the side chains of the 20 standard amino acids: six have alkyl groups (Section 12.8), three have aromatic groups (Section 13.11), two have sulfur-containing groups (Section 14.20), two have hydroxyl (alcohol) groups (Section 14.2), three have amino groups (Section 17.2), two have carboxyl groups (Section 16.1), and two have amide groups (Section 17.12).

20.2 AMINO ACIDS: THE BUILDING BLOCKS FOR PROTEINS An amino acid is an organic compound that contains both an amino (! NH2) group and a carboxyl (! COOH) group. The amino acids found in proteins are always a-amino acids. An ␣-amino acid is an amino acid in which the amino group and the carboxyl group are attached to the -carbon atom. The general structural formula for an -amino acid is a-Carbon atom Amino group

R Side chain A H2NOCO COOH A H

Carboxyl group

The R group present in an a-amino acid is called the amino acid side chain. The nature of this side chain distinguishes a-amino acids from each other. Side chains vary in size, shape, charge, acidity, functional groups present, hydrogen-bonding ability, and chemical reactivity. Over 700 different naturally occurring amino acids are known, but only 20 of them, called standard amino acids, are normally present in proteins. A standard amino acid is one of the 20 a-amino acids normally found in proteins. The structures of the 20 standard amino acids are given in Table 20.1. Within Table 20.1, amino acids are grouped according to side-chain polarity. In this system there are four categories: (1) nonpolar amino acids, (2) polar neutral amino acids, (3) polar acidic amino acids, and (4) polar basic amino acids. This classification system gives insights into how various types of amino acid side chains help determine the properties of proteins (Section 20.11). A nonpolar amino acid is an amino acid that contains one amino group, one carboxyl group, and a nonpolar side chain. When incorporated into a protein, such amino acids are hydrophobic (“water-fearing”); that is, they are not attracted to water molecules. They are generally found in the interior of proteins, where there is limited contact with water. There are nine nonpolar amino acids. Tryptophan is a borderline member of this group because water can weakly interact through hydrogen bonding with the NH ring location on tryptophan’s side-chain ring structure. Thus, some textbooks list tryptophan as a polar neutral amino acid. The three types of polar amino acids have varying degrees of affinity for water. Within a protein, such amino acids are said to be hydrophilic (“water-loving”). Hydrophilic amino acids are often found on the surfaces of proteins. A polar neutral amino acid is an amino acid that contains one amino group, one carboxyl group, and a side chain that is polar but neutral. In solution at physiological pH, the side chain of a polar neutral amino acid is neither acidic nor basic. There are six polar neutral amino acids. These amino acids are more soluble in water than the nonpolar amino acids as, in each case, the R group present can hydrogen bond to water. A polar acidic amino acid is an amino acid that contains one amino group and two carboxyl groups, the second carboxyl group being part of the side chain. In solution at physiological pH, the side chain of a polar acidic amino acid bears a negative charge; the side-chain carboxyl group has lost its acidic hydrogen atom. There are two polar acidic amino acids: aspartic acid and glutamic acid. A polar basic amino acid is an amino acid that contains two amino groups and one carboxyl group, the second amino group being part of the side chain. In solution at physiological pH, the side chain of a polar basic amino acid bears a positive charge; the nitrogen atom of the amino group has accepted a proton (basic behavior; Section 17.6). There are three polar basic amino acids: lysine, arginine, and histidine. The names of the standard amino acids are often abbreviated using three-letter codes. Except in four cases, these abbreviations are the first three letters of the amino acid’s name. In addition, a new one-letter code for amino acid names is currently gaining popularity (particularly in computer applications). Both sets of abbreviations are used extensively in specifying the amino acid make-up of protein. Both sets of abbreviations are given in Table 20.1.

TABLE 20.1 The 20 Standard Amino Acids, Grouped According to Side-Chain Polarity Below each amino acid’s structure are its name (with pronunciation), its three-letter abbreviation, and its one-letter abbreviation. Nonpolar Amino Acids

CH3 CH3 CH

CH3 H2N C

H2N C

COOH

H2N C

COOH

Glycine (Gly, G) GLY-seen

H2N C

COOH

Alanine (Ala, A) AL-ah-neen

CH3 CH

Valine (Val, V) VAY-leen

COOH

H

Leucine (Leu, L) LOO-seen CH3

Isoleucine (Ile, I) eye-so-LOO-seen NH

S CH2

CH2 CH2 H2C HN C

H2 N C

COOH

H

H

H

H

CH2

CH2

CH3 CH

CH3

H

CH3

CH2

CH2 H2N C

COOH

H2N C

COOH

COOH

H2N C

H

H

H

Proline (Pro, P) PRO-leen

CH2

Phenylalanine (Phe, F) fen-il-AL-ah-neen

COOH

H

Methionine (Met, M) me-THIGH-oh-neen

Tryptophan (Trp, W) TRIP-toe-fane

Polar Neutral Amino Acids

OH

SH

CH3

CH2

CH2

CH

H2N C

COOH

H2N C H

H

Serine (Ser, S) SEER-een

NH2

C

NH2

COOH

Asparagine (Asn, N) ah-SPAR-ah geen Polar Acidic Amino Acids

Threonine (Thr, T) THREE-oh-neen OH

CH2

H2N C

COOH

H2N C

COOH

H

H

H

COOH

CH2

CH2

CH2 H2N C

C

H2N C

H

Cysteine (Cys, C) SIS-teh-een O

O

COOH

OH

Glutamine (Gln, Q) GLU-tah-meen

Tyrosine (Tyr, Y) (TIE-roe-seen)

Polar Basic Amino Acids

NH2

O O

OH

OH C

C

CH2

CH2

CH2

H2N C

COOH

H

Aspartic acid (Asp, D) ah-SPAR-tic acid

H2N C

HN N CH2

COOH

H

Glutamic acid (Glu, E) glu-TAM-ic acid

H2N C

COOH

H

Histidine (His, H) HISS-tuh-deen

NH2

C

CH2

NH

CH2

CH2

CH2

CH2

CH2

CH2

H2N C

COOH

H

Lysine (Lys, K) LYE-seen

H2N C

NH

COOH

H

Arginine (Arg, R) ARG-ih-neen

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Chapter 20 Proteins

c

HEMICAL

onnections

The Essential Amino Acids

All of the amino acids in Table 20.1 are necessary constituents of human protein. Adequate amounts of 11 of the 20 amino acids can be synthesized from carbohydrates and lipids in the body if a source of nitrogen is also available. Because the human body is incapable of producing 9 of these 20 acids fast enough or in sufficient quantities to sustain normal growth, these 9 amino acids, called essential amino acids, must be obtained from food. An essential amino acid is an amino acid needed in the human body that must be obtained from dietary sources because it cannot be synthesized within the body from other substances in adequate amounts. The following table lists the essential amino acids for humans. The Essential Amino Acids for Humans arginine* histidine isoleucine leucine lysine

methionine phenylalanine threonine tryptophan valine

*Arginine is required for growth in children but is not required by adults.

The human body can synthesize small amounts of some of the essential amino acids, but not enough to meet its needs, especially in the case of growing children.

A complete dietary protein is a protein that contains all the essential amino acids in approximately the same relative amounts in which the human body needs them. A complete dietary protein may or may not contain all the nonessential amino acids. Most animal proteins, including casein from milk and proteins found in meat, fish, and eggs, are complete proteins, although gelatin is an exception (it lacks tryptophan). Proteins from plants (vegetables, grains, and legumes) have quite diverse amino acid patterns and some tend to be limited in one or more essential amino acids. Some plant proteins (for example, corn protein) are far from complete. Others (for example, soy protein) are complete. Thus vegetarians must eat a variety of plant foods to obtain all of the essential amino acids in appropriate quantities. The following table lists the essential amino acid deficiencies associated with selected vegetables and grains. Amino Acids Missing in Selected Vegetables and Grains Food Source

Amino Acid Deficiency

soy wheat, rice, oats corn beans peas almonds, walnuts

none lysine lysine, tryptophan methionine, tryptophan methionine lysine, tryptophan

20.3 CHIRALITY AND AMINO ACIDS Glycine, the simplest of the standard amino acids, is achiral. All of the other standard amino acids are chiral.

Because only L amino acids are constituents of proteins, the enantiomer designation of L or D will be omitted in subsequent amino acid and protein discussions. It is understood that it is the L isomer that is always present.

Four different groups are attached to the a-carbon atom in all of the standard amino acids except glycine, where the R group is a hydrogen atom. R A H2NO CO COOH A H

This means that the structures of 19 of the 20 standard amino acids possess a chiral center (Section 18.4) at this location, so enantiomeric forms (left- and right-handed forms; Section 18.5) exist for each of these amino acids. With few exceptions (in some bacteria), the amino acids found in nature and in proteins are L isomers. Thus, as is the case with monosaccharides (Section 18.8), nature favors one mirror-image form over the other. Interestingly, for amino acids the L isomer is the preferred form, whereas for monosaccharides the D isomer is preferred. The rules for drawing Fischer projection formulas (Section 18.6) for amino acid structures follow. 1. The —COOH group is put at the top of the projection, the R group at the bottom. This positions the carbon chain vertically. 2. The —NH2 group is in a horizontal position. Positioning it on the left denotes the L isomer, and positioning it on the right denotes the D isomer.

20.4 Acid–Base Properties of Amino Acids Mirror

Figure 20.1 Designation of handedness in standard amino acid structures involves aligning the carbon chain vertically and looking at the position of the horizontally aligned !NH2 group. The L form has the !NH2 group on the left, and the D form has the !NH2 group on the right.

659

COOH

COOH NH2

H

NH2

H

R

R

L-Amino

acid

D-Amino

acid

Figure 20.1 shows molecular models that illustrate the use of these rules. Fischer projection formulas for both enantiomers of the amino acids alanine and serine follow. Two of the 19 chiral standard amino acids, isoleucine and threonine, possess two chiral centers (see Table 20.1). With two chiral centers present, four stereoisomers are possible for these amino acids. However, only one of the L isomers is found in proteins.

COOH H2N

H

COOH

COOH H

CH3

NH2

H2N

H

CH3

L-Alanine

CH2 A OH

D-Alanine

L -Serine

COOH H

NH2 CH2 A OH D-Serine

20.4 ACID–BASE PROPERTIES OF AMINO ACIDS In pure form, amino acids are white crystalline solids with relatively high decomposition points. (Most amino acids decompose before they melt.) Also, most amino acids are not very soluble in water because of strong intermolecular forces within their crystal structures. Such properties are those often exhibited by compounds in which charged species are present. Studies of amino acids confirm that they are charged species both in the solid state and in solution. Why is this so? Both an acidic group (9COOH) and a basic group (9NH2) are present on the same carbon in an a-amino acid. In drawing amino acid structures, where handedness designation is not required, the placement of the four groups about the a-carbon atom is arbitrary. From this point on in the text, we will draw amino acid structures such that the 9COOH group is on the right, the 9NH2 group is on the left, the R group points down, and the H atom points up. Drawing amino acids in this “arrangement” makes it easier to draw structures where amino acids are linked together to form longer amino acid chains.

Basic group

H A H2NOCO COOH A R

Acidic group

In Section 16.8, we learned that in neutral solution, carboxyl groups have a tendency to lose protons (H⫹), producing a negatively charged species: OCOOH ¡ OCOO 2 1 H1

In Section 17.6, we learned that in neutral solution, amino groups have a tendency to accept protons (H⫹), producing a positively charged species: O NH2 ⫹ H⫹

⫹

O NH3

Consistent with the behavior of these groups, in neutral solution, the 9COOH group of an amino acid donates a proton to the 9NH2 of the same amino acid. We can characterize this behavior as an internal acid–base reaction. The net result is that in neutral solution, amino acid molecules have the structure H A H3NOCO COO⫺ A R ⫹

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Chapter 20 Proteins

Strong intermolecular forces between the positive and negative centers of zwitterions are the cause of the high melting points of amino acids.

Such a molecule is known as a zwitterion, from the German term meaning “double ion.” A zwitterion is a molecule that has a positive charge on one atom and a negative charge on another atom, but which has no net charge. Note that the net charge on a zwitterion is zero even though parts of the molecule carry charges. In solution and also in the solid state, -amino acids exist as zwitterions. Zwitterion structure changes when the pH of a solution containing an amino acid is changed from neutral either to acidic (low pH) by adding an acid such as HCl or to basic (high pH) by adding a base such as NaOH. In an acidic solution, the zwitterion accepts a proton (H) to form a positively charged ion.

From this point on in the text, the structures of amino acids will be drawn in their zwitterion form unless information given about the pH of the solution indicates otherwise.

H A H3NOCO COO  H3O A R

H A H3NOCO COOH  H2O A R





Zwitterion (no net charge)

Positively charged ion



In basic solution, the O N H3 of the zwitterion loses a proton, and a negatively charged species is formed. H A H3NOCO COO  OH A R

H A  H2NOCO COO  H2O A R



B

Zwitterion (no net charge)

F

The ability of amino acids to react with both H3O and OH ions means that amino acid solutions can function as buffers (Section 10.12). The same is true for proteins, which are amino acid polymers (Section 20.1). The buffering action of proteins present in blood is a major function of such proteins.

Negatively charged ion

Thus, in solution, three different amino acid forms can exist (zwitterion, negative ion, and positive ion). The three species are actually in equilibrium with each other, and the equilibrium shifts with pH change. The overall equilibrium process can be represented as follows: H A H3NOCO COOH A R 

OH H3O

Acidic solution (low pH)

H A H3NOCO COO A R 

H A H2NOCO COO A R

OH H3O

Neutral solution (pH  7.0)

Basic solution (high pH)

In acidic solution, the positively charged species on the left predominates; nearly neutral solutions have the middle species (the zwitterion) as the dominant species; in basic solution, the negatively charged species on the right predominates.

EXAMPLE 20.1 Determining Amino Acid Form in Solutions of Various pH

Draw the structural form of the amino acid alanine that predominates in solution at each of the following pH values. a. pH  1.0 b. pH  7.0 c. pH  11.0 Solution

At low pH, both amino and carboxyl groups are protonated. At high pH, both groups have lost their protons. At neutral pH, the zwitterion is present.

a.

H A H3NOCO COOH A CH3 

pH  1.0 (net charge of 1)

b.

H A H3NOC O COO A CH3 

pH  7.0 (no net charge)

c.

H A H2NOC O COO A CH3 pH  11.0 (net charge of 1)

20.4 Acid–Base Properties of Amino Acids

Practice Exercise 20.1

Guidelines for amino acid form as a function of solution pH follow. Low pH:

High pH:

Draw the structural form of the amino acid valine that predominates in solution at each of the following pH values.

All acid groups are protonated (!COOH). All amino groups ⫹ are protonated (! N H3).

a. pH ⫽ 7.0 Answers: a.

All acid groups are deprotonated (!COO⫺). All amino groups are deprotonated (!NH2).

Neutral pH: All acid groups are deprotonated (!COO⫺). All amino groups are protonated ⫹ (!N H3).

The term protonated denotes gain of a H⫹ ion, and the term deprotonated denotes loss of a H⫹ ion.

Side-chain carboxyl groups are weaker acids than a-carbon carboxyl groups.

Isoelectric Points for the 20 Amino Acids Commonly Found in Proteins

Name

alanine arginine asparagine aspartic acid cysteine glutamic acid glutamine glycine histidine isoleucine leucine lysine methionine phenylalanine proline serine threonine tryptophan tyrosine valine

Isoelectric Point

6.01 10.76 5.41 2.77 5.07 3.22 5.65 5.97 7.59 6.02 5.98 9.74 5.74 5.48 6.48 5.68 5.87 5.88 5.66 5.97

b. pH ⫽ 12.0

H A H3NOCO COO⫺ A CH O CH3 A CH3

c. pH ⫽ 2.0

b.

⫹

H A H2NOC O COO⫺ A CH O CH3 A CH3

c.

H A H3NOC O COOH A CH O CH3 A CH3 ⫹

The previous discussion assumed that the side chain (R group) of an amino acid remains unchanged in solution as the pH is varied. This is the case for neutral amino acids but not for acidic or basic ones. For these latter compounds, the side chain can also acquire a charge because it contains an amino or a carboxyl group that can, respectively, gain or lose a proton. Because of the extra site that can be protonated or deprotonated, acidic and basic amino acids have four charged forms in solution. These four forms for aspartic acid, one of the acidic amino acids, are H A H3NOCO COOH A CH2 A COOH ⫹

Low-pH form (⫹1 charge)

TABLE 20.2

661

OH⫺ H3O⫹

H A H3NOCOCOO⫺ A CH2 A COOH ⫹

OH ⫺ H3O⫹

Moderately-low-pH form (no net charge) (zwitterion)

H A H3NOCOCOO⫺ A CH2 A COO⫺ ⫹

Intermediate-pH form (⫺1 net charge)

OH⫺ H3O⫹

H A H2NOCOCOO⫺ A CH2 A COO⫺ High-pH form (⫺2 net charge)

The existence of two low-pH forms for aspartic acid results from the two carboxyl groups being deprotonated at different pH values. For basic amino acids, two high-pH forms exist because deprotonation of the amino groups does not occur simultaneously. The side-chain amino group deprotonates before the a-amino group for histidine, but the opposite is true for lysine and arginine.

Isoelectric Points and Electrophoresis The amounts of the various forms of an amino acid — zwitterion, negative ion(s), and positive ion(s) — that are present in an aqueous solution of the amino acid vary with solution pH. There is no pH at which ionic amino acid forms are absent, but there is a pH at which there is an equal number of positive and negative charges present, which produces a “no net charge” situation. The “no net charge” pH value for an amino acid solution is called its isoelectric point. An isoelectric point is the pH at which an amino acid solution has no net charge because an equal number of positive and negative charges are present. At the isoelectric point, almost all amino acid molecules in a solution (more than 99%) are present in their zwitterion form. Every amino acid has a different isoelectric point. Fifteen of the 20 amino acids, those with nonpolar or polar neutral side chains (Table 20.1), have isoelectric points in the range of 4.8–6.3. The three basic amino acids have higher isoelectric points and the two acidic amino acids have lower ones. Table 20.2 lists the isoelectric points for the 20 standard amino acids. The isoelectric point of an amino acid is measured by observing its behavior in an electric field. In an electric field, a charged molecule is attracted to (migrates toward) the electrode of opposite charge. At a high pH, an amino acid has a net negative charge and migrates toward the positive electrode. At a low pH, the opposite is true; with a net positive charge, the amino acid migrates toward the negative electrode. At the isoelectric point, migration does not occur because the zwitterions present have no net charge.

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Chapter 20 Proteins

Figure 20.2 Separation, at a pH of

Lys (moves toward negative electrode)

Mix of Lys, Phe, Glu on moistened paper

5.5, of the three amino acids Lys, Phe, and Glu using electrophoresis.

Power source off

Phe (no Glu (moves toward movement) positive electrode)

Power source on

Negative electrode

Positive electrode

Positive electrode

Negative electrode

Mixtures of amino acids in solution can be separated by using their different migration patterns at various pH values. This type of analytical separation is called electrophoresis. Electrophoresis is the process of separating charged molecules on the basis of their migration toward charged electrodes associated with an electric field. Figure 20.2 schematically shows the separation of the amino acids Lys, Phe, and Glu by electrophoresis. At a pH of 5.5, these amino acids exist in the following forms: 

NH3 COO



COO

H3N



H3N

COO

Phe (no net charge)

Lys (l charge)



COO

H3N

Glu (l charge)

When a current is applied, Phe does not move (it has no net charge); Lys, because of its positive charge, migrates toward the negative electrode; and Glu, with a negative charge, moves toward the positive electrode. Proteins, which are amino acid polymers (Section 20.8), also have isoelectric points and also can be separated via electrophoresis techniques.

EXAMPLE 20.2 Migration Patterns of Amino Acids at Various pH Values in an Electric Field

Predict the direction of migration (if any) toward the positively or negatively charged electrode for the following amino acids in solutions of the specified pH. Write “isoelectric” if no migration occurs. a. Lysine at pH  7.0 b. Glutamic acid at pH  7.0 c. Serine at pH  1.0 Solution

a. Lysine at pH  7.0

H A H3NOC O COO A CH2 A CH2 A CH2 A CH2 A  NH3 

Net positive charge (2 “” and 1 “”) Migrates toward negatively charged electrode

20.6 Peptides

b. Glutamic acid at pH  7.0

H A H3NOC O COO A CH2 A CH2 A COO

Net negative charge (1 “” and 2 “”)



c. Serine at pH  1.0

663

Migrates toward positively charged electrode

H A H3NOC O COOH A CH2 A OH

One positive charge



Migrates toward negatively charged electrode

Practice Exercise 20.2 Predict the direction of migration (if any) toward the positively or negatively charged electrode for the following amino acids in solutions of the specified pH. Write “isoelectric” if no migration occurs. a. Lysine at pH  12.0

b. Glutamic acid at pH  2.0

c. Serine at pH  5.68

Answers: a. Toward positively charged electrode; b. Toward negatively charged electrode; c. Isoelectric

20.5 CYSTEINE: A CHEMICALLY UNIQUE AMINO ACID Cysteine is the only standard amino acid (Table 20.1) that has a side chain that contains a sulfhydryl group (9SH group; Section 14.20). The presence of this sulfhydryl group imparts to cysteine a chemical property that is unique among the standard amino acids. Cysteine, in the presence of mild oxidizing agents, readily dimerizes, that is, reacts with another cysteine molecule to form a cystine molecule. (A dimer is a molecule that is made up of two like subunits.) In cystine, the two cysteine residues are linked via a covalent disulfide bond. Cystine contains two cysteine residues linked by a disulfide bond.



H3N

CH



COO  H3N

CH2 SH Cysteine

CH

COO

CH2

CH2

C 

SH

Disulfide bond

COO S

S

CH2

C 

NH3

Cysteine

COO

NH3

Cystine

The covalent disulfide bond of cystine is readily broken, using reducing agents, to regenerate two cysteine molecules. This oxidation–reduction behavior involving sulfhydryl groups and disulfide bonds was previously encountered in Section 14.20 when the reactions of thioalcohols were considered. SH  HS

Oxidation Reduction

S

S

 2H

As we shall see in Section 20.10, the formation of disulfide bonds between cysteine residues present in protein molecules has important consequences relative to protein structure and protein shape.

20.6 PEPTIDES Under proper conditions, amino acids can bond together to produce an unbranched chain of amino acids. The length of the amino acid chain can vary from a few amino acids to many amino acids. Representative of such chains is the following five-amino-acid chain.

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Chapter 20 Proteins

Amino acid O Amino acid O Amino acid O Amino acid O Amino acid

Such a chain of covalently linked amino acids is called a peptide. A peptide is an unbranched chain of amino acids, each joined to the next by a peptide bond. Peptides are further classified by the number of amino acids present in the chain. A compound containing two amino acids is specifically called a dipeptide; three amino acids joined together in a chain constitute a tripeptide; and so on. The name oligopeptide is loosely used to refer to peptides with 10 to 20 amino acid residues, and the name polypeptide is used to refer to longer peptides. A polypeptide is a long unbranched chain of amino acids, each joined to the next by a peptide bond.

Nature of the Peptide Bond The bonds that link amino acids together in a peptide chain are called peptide bonds. There are four peptide bonds present in a pentapeptide. Amino acid O Amino acid O Amino acid O Amino acid O Amino acid Peptide bond

Peptide bond

Peptide bond

Peptide bond

The nature of the peptide bond becomes apparent by reconsidering a chemical reaction previously encountered. In Section 17.16, we learned that a carboxylic acid and an amine can react to produce an amide. The general equation for this reaction is O H B A RO CO OH  HO NOR Acid

O H B A RO C O NO R  H2O

Amine

Amide

Two amino acids can combine in a similar way — the carboxyl group of one amino acid interacts with the amino group of the other amino acid. The products are a molecule of water and a molecule containing the two amino acids linked by an amide bond. Amide bond formation is an example of a condensation reaction.

H H A A   H3NO CO COO  H3NO COCOO A A R1 R2 

H O H H A B A A H3NO COCONO CO COO  H2O A A R2 R1 

Amide bond

Removal of the elements of water from the reacting carboxyl and amino groups and the ensuing formation of the amide bond are better visualized when expanded structural formulas for the reacting groups are used. O H B A O CO O  H ONO A H Carboxyl group (O COO)

A peptide chain has directionality because its two ends are different. There is an N-terminal end and a C-terminal end. By convention, the direction of the peptide chain is always N-terminal end S C-terminal end The N-terminal end is always on the left, and the C-terminal end is always on the right.

Amino group  (H3NO)

O H B A O C ON O  H2O Amide bond

In amino acid chemistry, amide bonds that link amino acids together are given the specific name of peptide bond. A peptide bond is a covalent bond between the carboxyl group of one amino acid and the amino group of another amino acid. In all peptides, long or short, the amino acid at one end of the amino acid sequence 1 has a free H3N group, and the amino acid at the other end of the sequence has a free 1 COO group. The end with the free H3N group is called the N-terminal end, and the end with the free COO group is called the C-terminal end. By convention, the sequence of amino acids in a peptide is written with the N-terminal end amino acid on the left. The individual amino acids within a peptide chain are called amino acid residues. An

20.6 Peptides

665

amino acid residue is the portion of an amino acid structure that remains, after the release of H2O, when an amino acid participates in peptide bond formation as it becomes part of a peptide chain. The structural formula for a peptide may be written out in full, or the sequence of amino acids present may be indicated by using the standard three-letter amino acid abbreviations. The abbreviated formula for the tripeptide H O H H O H H A B A A B A A H3NOCO CONO COCONO CO COO A A A H CH2 CH3 A OH 

N-terminal end

Glycine

Alanine

C-terminal end

Serine

which contains the amino acids glycine, alanine, and serine, is Gly–Ala–Ser. When we use this abbreviated notation, by convention, the amino acid at the N-terminal end of the peptide is always written on the left. The repeating sequence of peptide bonds and a-carbon 9CH groups in a peptide is referred to as the backbone of the peptide. O CH R1

C

O NH

CH

C

O NH

R2

CH

C

R3

NH

CH R4

Backbone of peptide (in color)

The R group side chains are considered substituents on the backbone rather than part of the backbone. Thus, structurally, a peptide has a regularly repeating part (the backbone) and a variable part (the sequence of R groups). It is the variable R group sequence that distinguishes one peptide from another.

EXAMPLE 20.3 Converting an Abbreviated Peptide Formula to a Structural Peptide Formula

Draw the structural formula for the tripeptide Ala–Gly–Val. Solution

Step 1: The N-terminal end of the peptide involves alanine. Its structure is written first.

H A H3NO C OCOO A CH3 

Step 2: The structure of glycine is written to the right of the alanine structure, and a peptide bond is formed between the two amino acids by removing the elements of H2O and bonding the N of glycine to the carboxyl C of alanine.

H H A A  H3NO CO COO  H3NO CO COO A A CH3 H 

H O H H A B A A H3NOC OC ONOC O COO  H2O A A H CH3 

(continued)

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Chapter 20 Proteins

Step 3: To the right of the just-formed dipeptide, draw the structure of valine. Then repeat Step 2 to form the desired tripeptide.

H H O H H A A B A A ⫹ ⫺ H3NO COC ONO CO COO ⫹ H3NO CO COO⫺ A A A CH3 H CH O CH3 ⫹

A

CH3 H O H H O H H A B A A B A A H3NOC OCO NOC OC O NO CO COO⫺ ⫹ H2O A A A CH O CH3 H CH3 ⫹

A

CH3

Practice Exercise 20.3 Draw the structural formula for the tripeptide Cys–Ala–Gly. Answer:

H O H H O H H A B A A B A A H3NOC OCO NOC OC O NOCO COO⫺ A A A H CH3 CH2 A SH ⫹

Peptide Nomenclature IUPAC rules for naming small peptides are as follows: The C-terminal amino acid residue (located at the far right of the structure) keeps its full amino acid name. Rule 2: All of the other amino acid residues have names that end in -yl. The -yl suffix replaces the -ine or -ic acid ending of the amino acid name, except for tryptophan (tryptophyl), cysteine (cysteinyl), glutamine (glutaminyl), and asparagine (asparaginyl). Rule 3: The amino acid naming sequence begins at the N-terminal amino acid residue. Rule 1:

EXAMPLE 20.4 Determining IUPAC Names for Small Peptides

Assign IUPAC names to each of the following small peptides. a. Glu–Ser–Ala b. Gly–Tyr–Leu–Val Solution

a. The three amino acids present are glutamic acid, serine, and alanine. Alanine, the C-terminal residue (on the far right), keeps its full name. The other amino acid residues in the peptide receive “shortened” names that end in -yl. The -yl replaces the -ine or -ic acid ending of the amino acid name. Thus glutamic acid becomes glutamyl serine becomes seryl alanine remains alanine The IUPAC name, which lists the amino acids in the sequence from N-terminal residue to C-terminal residue, becomes glutamylserylalanine.

20.7 Biochemically Important Small Peptides

667

b. The four amino acids present are glycine, tyrosine, leucine, and valine. Proceeding as in part a, we note that glycine becomes glycyl tyrosine becomes tyrosyl leucine becomes leucyl valine remains valine Combining these individual names gives the IUPAC name glycyltyrosylleucylvaline. The complete name for a small peptide should actually include a handedness designation (L-designation; Section 20.3) before the name of each residue. For example the dipeptide serylglycine (Ser–Gly) should actually be L-seryl–L-glycine (L-Ser–L-Gly). The L-handedness designation is, however, usually not included because it is understood that all amino acids present in a peptide, unless otherwise noted, are L enantiomers.

Practice Exercise 20.4 Assign IUPAC names to each of the following small peptides. a. Gly–Ala–Leu

b. Gly–Tyr–Ser–Ser

Answers: a. Glycylalanylleucine; b. Glycyltyrosylserylserine

Isomeric Peptides Peptides that contain the same amino acids but in different order are different molecules (constitutional isomers) with different properties. For example, two different dipeptides can be formed from one molecule of alanine and one molecule of glycine. Amino acid sequence in a peptide has biochemical importance. Isomeric peptides give different biochemical responses; that is, they have different biochemical specificities.

For a peptide containing one each of n different kinds of amino acids, the number of constitutional isomers is given by n! (n factorial). 5!  5  4  3  2  1  120

H O H H A B A A H3NOCO CONO CO COO A A CH3 H AlaGly 

H O H H A B A A H3NOCO CONOCO COO A A CH3 H Gly  Ala 

In the first dipeptide, the alanine is the N-terminal residue, and in the second molecule, it is the C-terminal residue. These two compounds are isomers with different chemical and physical properties. The number of isomeric peptides possible increases rapidly as the length of the peptide chain increases. Let us consider the tripeptide Ala–Ser–Cys as another example. In addition to this sequence, five other arrangements of these three components are possible, each representing another isomeric tripeptide: Ala–Cys–Ser, Ser–Ala–Cys, Ser– Cys–Ala, Cys–Ala–Ser, and Cys–Ser–Ala. For a pentapeptide containing 5 different amino acids, 120 isomers are possible.

20.7 BIOCHEMICALLY IMPORTANT SMALL PEPTIDES Many relatively small peptides have been shown to be biochemically active. Functions for them include hormonal action, neurotransmission, and antioxidant activity.

Small Peptide Hormones The two best-known peptide hormones, both produced by the pituitary gland, are oxytocin and vasopressin. Each hormone is a nonapeptide (nine amino acid residues) with six of the residues held in the form of a loop by a disulfide bond formed from the interaction of two

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Chapter 20 Proteins

Oxytocin plays a role in stimulating the flow of milk in a nursing mother. The baby’s suckling action sends nerve signals to the mother’s brain, triggering the release of oxytocin, via the blood, to the mammary glands. The oxytocin causes muscle contraction in the mammary gland, forcing out milk. As suckling continues, more oxytocin is released and more milk is available for the baby.

cysteine residues (Section 20.5). Structurally, these nonapeptides differ in the amino acid present in positions 3 and 8 of the peptide chain. In both structures an amide group replaces the C terminal single-bonded oxygen atom. O 1 Cys 2

S

6 Cys

S

5

Tyr Ile 3 Phe

4

7 Pro

8

Leu Arg

9 Gly

C

NH2

Asn Oxytocin Vasopressin

Gln

Oxytocin regulates uterine contractions and lactation. Vasopressin regulates the excretion of water by the kidneys; it also affects blood pressure.

Small Peptide Neurotransmitters Enkephalins are pentapeptide neurotransmitters produced by the brain itself that bind at receptor sites in the brain to reduce pain. The two best-known enkephalins are Metenkephalin and Leu-enkephalin, whose structures are Met-enkephalin: Tyr–Gly–Gly–Phe–Met Leu-enkephalin: Tyr–Gly–Gly–Phe–Leu The two enkephalins differ structurally only in the amino acid at the end of the chain. The pain-reducing effects of enkephalin action play a role in the “high” reported by long-distance runners, in the competitive athlete’s managing to finish the game despite being injured, and in the pain-relieving effects of acupuncture. The action of the prescription painkillers morphine and codeine is based on their binding at the same receptor sites in the brain as the naturally occurring enkephalins.

Small Peptide Antioxidants B

F

Other antioxidants previously considered are BHA and BHT (Section 14.13) and -carotene (Section 13.7).

The tripeptide glutathione (Glu–Cys–Gly) is present in significant concentrations in most cells and is of considerable physiological importance as a regulator of oxidation–reduction reactions. Specifically, glutathione functions as an antioxidant (Section 14.13), protecting cellular contents from oxidizing agents such as peroxides and superoxides (highly reactive forms of oxygen often generated within the cell in response to bacterial invasion) (Section 23.11). The tripeptide structure of glutathione has an unusual feature. The amino acid Glu, an acidic amino acid, is bonded to Cys through the side-chain carboxyl group rather than through its a-carbon carboxyl group. O 

H3N

CH

CH2

COO Glu

CH2

C

O NH

CH CH2 SH Cys

C

NH

CH

COO

H Gly

20.8 GENERAL STRUCTURAL CHARACTERISTICS OF PROTEINS B

F

Proteins are the second type of biochemical polymer we have encountered; the other was polysaccharides (Section 18.14). Protein monomers are amino acids, whereas polysaccharide monomers are monosaccharides.

In Section 20.1, we defined a protein simply as a naturally occurring, unbranched polymer in which the monomer units are amino acids. A more specific protein definition is now in order. A protein is a peptide in which at least 40 amino acid residues are present. The defining line governing the use of the term protein — 40 amino acid residues — is an arbitrary line. The terms polypeptide and protein are often used interchangeably; a protein is a relatively long polypeptide. The key point is that the term protein is reserved for

20.8 General Structural Characteristics of Proteins

669

peptides with a large number of amino acids; it is not correct to call a tripeptide a protein. Over 10,000 amino acid residues are present in several proteins; 400–500 amino acid residues are common in proteins; small proteins contain 40–100 amino acid residues. More than one peptide chain may be present in a protein. On this basis, proteins are classified as monomeric or multimeric. A monomeric protein is a protein in which only one peptide chain is present. Large proteins, those with many amino acid residues, usually are multimeric. A multimeric protein is a protein in which more than one peptide chain is present. The peptide chains present in multimeric proteins are called protein subunits. The protein subunits within a multimeric protein may all be identical to each other or different kinds of subunits may be present. Proteins with up to 12 subunits are known. The small protein insulin, which functions as a hormone in the human body, is a multimeric protein with two protein subunits; one subunit contains 21 amino acid residues and the other 30 amino acid residues. The structure of insulin is considered in more detail in Section 20.11. Proteins, on the basis of chemical composition, are classified as simple or complex. A simple protein is a protein in which only amino acid residues are present. More than one protein subunit may be present in a simple protein, but all subunits contain only amino acids. A conjugated protein is a protein that has one or more nonamino acid entities present in its structure in addition to one or more peptide chains. These non-amino acid components, which may be organic or inorganic, are called prosthetic groups. A prosthetic group is a non-amino acid group present in a conjugated protein. Conjugated proteins may be further classified according to the nature of the prosthetic group(s) present. Lipoproteins contain lipid prosthetic groups, glycoproteins contain carbohydrate groups, metalloproteins contain a specific metal, and so on (see Table 20.3). Some proteins contain more than one type of prosthetic group. In general, prosthetic groups have important roles in the biochemical functions for conjugated proteins. Several examples of glycoproteins and lipoproteins are discussed in Sections 20.17 and 20.18, respectively. In general, the three-dimensional structures of proteins, even those with just a single peptide chain, are more complex than those of carbohydrates and lipids — the biomolecules discussed in the two previous chapters. Our approach to describing and understanding this complexity in protein structure involves considering this structure at four levels. These four protein structural levels, listed in order of increasing complexity, are primary structure, secondary structure, tertiary structure, and quaternary structure. They are the subject matter for the next four sections of this chapter. TABLE 20.3 Types of Conjugated Proteins Class

Prosthetic Group

Specific Example

Function of Example

hemoproteins

heme unit

hemoglobin myoglobin

carrier of O2 in blood oxygen binder in muscles

lipoproteins

lipid

low-density lipoprotein (LDL) high-density lipoprotein (HDL)

lipid carrier lipid carrier

glycoproteins

carbohydrate

gamma globulin mucin interferon

antibody lubricant in mucous secretions antiviral protection

phosphoproteins

phosphate group

glycogen phosphorylase

enzyme in glycogen phosphorylation

nucleoproteins

nucleic acid

ribosomes viruses

site for protein synthesis in cells self-replicating, infectious complex

metalloproteins

metal ion

iron–ferritin zinc–alcohol dehydrogenase

storage complex for iron enzyme in alcohol oxidation

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Chapter 20 Proteins

20.9 PRIMARY STRUCTURE OF PROTEINS

Figure 20.3 The British biochemist Frederick Sanger (1918– ) determined the primary structure of the protein hormone insulin in 1953. His work is a landmark in biochemistry because it showed for the first time that a protein has a precisely defined amino acid sequence. Sanger was awarded the Nobel Prize in chemistry in 1958 for this work. Later, in 1980, he was awarded a second Nobel Prize in chemistry, this time for work that involved the sequencing of units in nucleic acids (Chapter 22).

Primary protein structure is the order in which amino acids are linked together in a protein. Every protein has its own unique amino acid sequence. Primary protein structure always involves more than just the numbers and kinds of amino acids present; it also involves the order of attachment of the amino acids to each other through peptide bonds. Insulin, the hormone that regulates blood-glucose levels, was the first protein for which primary structure was determined; the “sequencing” of its 51 amino acids was completed in 1953, after 8 years of work by the British biochemist Frederick Sanger (see Figure 20.3). Today, primary structures are known for many thousands of proteins, and the sequencing procedures involve automated methods that require relatively short periods of time (days). Figure 20.4 shows the primary structure of myoglobin, a protein involved in oxygen transport in muscles; it contains 153 amino acids assembled in the particular, definite order shown in this diagram. The primary structure of a specific protein is always the same regardless of where the protein is found within an organism. The structures of certain proteins are even similar +

Lys

NH3

Asp

Gln Ala

Phe

Leu Glu

Ser

Phe

Gly

Phe

Lys

Leu

His

Leu

Arg

Leu

Lys

His

Pro

Ala

Ala

Lys

Ser

Glu

Leu

Lys

Thr

Lys

Asp

Asp

Leu

Lys

Ile

Lys

Asp

Met

Gly

Thr

Ser

Glu

His

Met

Ala

Glu

Glu

Glu

Ala

Lys

Ala

Ser

Trp

Pro

Asp

Glu

Ile

Gly

Asn

Gln

His

Glu

His

Pro

Gln

Tyr

Leu

Gly

Met

His

Val

Ala

Lys

Val

Lys

Lys

Gly

Lys

Asp

Glu

Leu

Phe

Ala

Lys

Tyr

Ala

Leu

Asn

Leu

Ser

Lys

Leu

Gly

Gly

Val

Arg

Glu

Lys

Glu

Phe

Phe

Trp

Ile

Asp

Leu

Phe

Asp

Gln

Gly

Leu

Leu

Ile

Ile

Gly

Gly

Lys

Val

Lys

Gly

Ser

Pro

Val

Glu

Lys

Gly

Glu

His

Glu

Gln

His

Leu

Cys

Lys

Ala

Gly

Gly

Ala

Ile

Ser

Asp

His

Ala

Thr

Ile

Gln

Ile

Gly Pro

Leu

Thr Val

COO–

Leu

Gln Val

Figure 20.4 The primary structure of human myoglobin. This diagram gives only the sequence of the amino acids present and conveys no information about the actual threedimensional shape of the protein. The “wavy” pattern for the 153 amino acid sequence was chosen to minimize the space used to present the needed information. The actual shape of the protein is determined by secondary and tertiary levels of protein structure, levels yet to be discussed.

20.10 Secondary Structure of Proteins

c

671

HEMICAL

onnections

Substitutes for Human Insulin

In humans, an insufficient production of insulin results in the disease diabetes mellitus. Treatment of this disease often involves giving the patient extra insulin via subcutaneous injection. For many years, because of the limited availability of human insulin, most insulin used by diabetics was obtained from the pancreases of slaughter-house animals. Such animal insulin, primarily from cows and pigs, was used by most diabetics without serious side effects because it is structurally very similar to human insulin. Immunological reactions gradually do increase over time, however, because the animal insulin is foreign to the human body. A comparison of the primary structure of human insulin with pig and cow insulins shows differences at only 4 of the 51 amino acid positions: positions 8, 9, and 10 on chain A and position 30 on chain B (see Figure 20.11 and the following table).

The primary structure of a protein is the sequence of amino acids in a protein chain — that is, the order in which the amino acids are connected to each other.

Chain A

Chain B

Species

#8

#9

#10

#30

human pig (porcine) cow (bovine)

Thr Thr Ala

Ser Ser Ser

Ile Ile Val

Thr Ala Ala

The dependence of diabetics on animal insulin has declined because of the availability of human insulin produced by genetically engineered bacteria (Section 22.14). These bacteria carry a gene that directs the synthesis of human insulin. Such bacteria-produced insulin is fully functional. All diabetics now have the choice of using human insulin or using animal insulin. Many still continue to use the animal insulin because it is cheaper.

among different species of animals. For example, the primary structures of insulin in cows, pigs, sheep, and horses are very similar both to each other and to human insulin. Until recently, this similarity was particularly important for diabetics who required supplemental injections of insulin. (See the Chemical Connections feature above.) An analogy is often drawn between the primary structure of proteins and words. Words, which convey information, are formed when the 26 letters of the English alphabet are properly sequenced. Proteins are formed from proper sequences of the 20 standard amino acids. Just as the proper sequence of letters in a word is necessary for it to make sense, the proper sequence of amino acids is necessary to make biochemically active protein. Furthermore, the letters that form a word are written from left to right, as are amino acids in protein formulas. As any dictionary of the English language will document, a tremendous variety of words can be formed by different letter sequences. Imagine the number of amino acid sequences possible for a large protein. There are 1.55  1066 sequences possible for the 51 amino acids found in insulin! From these possibilities, the body reliably produces only one, illustrating the remarkable precision of life processes. From the simplest bacterium to the human brain cell, only those amino acid sequences needed by the cell are produced. The fascinating process of protein biosynthesis and the way in which genes in DNA direct this process will be discussed in Chapter 22.

20.10 SECONDARY STRUCTURE OF PROTEINS Secondary protein structure is the arrangement in space adopted by the backbone portion of a protein. The two most common types of secondary structure are the alpha helix ( helix) and the beta pleated sheet (  pleated sheet). The type of interaction responsible for both of these types of secondary structure is hydrogen bonding (Section 7.13) between a carbonyl oxygen atom of a peptide linkage and the hydrogen atom of an amino group of another peptide linkage farther along the backbone. Information about the geometry associated with these peptide linkages is helpful in understanding how hydrogen bonding interactions occur between peptide linkages of a protein backbone. Important geometrical considerations are: 1. The peptide linkages are essentially planar. This means that for two amino acids linked through a peptide linkage, six atoms lie in the same plane: the -carbon atom and the C " O group from the first amino acid and the N–H group and the -carbon atom from the second amino acid.

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Chapter 20 Proteins

N-terminal end

C-terminal end

O

H

C

O R

R

H

O

O

H

R

R

N N

Cα

H R

R

N

Plane of peptide bond

H

R

N

Cα

H

O

N

C-terminal end

R

N

N

O

H

H

R

R H

O

N-terminal end

Figure 20.5 The hydrogen bonding between the carbonyl oxygen atom of one peptide linkage and the amide hydrogen atom of another peptide linkage.

2. The planar peptide linkage structure has considerable rigidity, which means that rotation of groups about the C 9 N bond is hindered, and cis–trans isomerism is possible about this bond. The trans isomer orientation is the preferred orientation, as shown in the preceding diagram. The O atom of the C " O group and the H atom of the N 9 H group are positioned trans to each other. Figure 20.5 shows the hydrogen bonding possibilities that exist between carbonyl oxygen atoms and amide hydrogen atoms associated with different peptide linkages in a protein backbone. The protein backbone segments shown can be two segments of the same backbone or two segments from different backbones. We consider both of these situations in further detail in this section.

The Alpha Helix

The hydrogen bonding present in an a helix is intramolecular. In a b pleated sheet, the hydrogen bonding can be intermolecular (between two different chains) or intramolecular (a single chain folding back on itself).

An alpha helix structure is a protein secondary structure in which a single protein chain adopts a shape that resembles a coiled spring (helix), with the coil configuration H H maintained by hydrogen bonds. The hydrogen bonds are between ENOH and ECPO groups of every fourth amino acid, as is shown diagrammatically in Figure 20.6. Proteins have varying amounts of a-helical secondary structure, ranging from a few percent to nearly 100%. In an a helix, all of the amino acid side chains (R groups) lie outside the helix; there is not enough room for them in the interior. Figure 20.6d illustrates this situation.

The Beta Pleated Sheet A beta pleated sheet structure is a protein secondary structure in which two fully extended protein chain segments in the same or different molecules are held together by

Figure 20.6 Four representations of the a helix protein secondary structure. (a) Arrangement of protein backbone with no detail shown. (b) Backbone arrangement with hydrogen-bonding interactions shown. (c) Backbone atomic detail shown, as well as hydrogen-bonding interactions. (d) Top view of an a helix showing that amino acid side chains (R groups) point away from the long axis of the helix.

C

Carbon Nitrogen Hydrogen Oxygen Side group

O C C

O

H O C

H

N C

O

H O H

N

C

N

O

N C O

H N

H

H N

N

(a)

(b)

(c)

(d)

673

20.10 Secondary Structure of Proteins

hydrogen bonds. Hydrogen bonds form between oxygen and hydrogen peptide linkage atoms that are either in different parts of a single chain that folds back on itself (intrachain bonds) or between atoms in different peptide chains in those proteins that contain more than one chain (interchain bonds). In molecules where the  pleated sheet involves a single molecule, several U-turns in the protein chain arrangement are needed in order to form the structure. C-terminal end

N-terminal end

The  pleated sheet is found extensively in the protein of silk. Because such proteins are already fully extended, silk fibers cannot be stretched. When wool, which has an  helix structure, becomes wet, it stretches as hydrogen bonds of the helix are broken. The wool returns to its original shape as it dries. Wet stretched wool, dried under tension, maintains its stretched length because it has assumed a  pleated sheet configuration.

This “U-turn structure” is the most frequently encountered type of  pleated sheet structure. Figure 20.7a shows a representation of the  pleated sheet structure that occurs when portions of two different peptide chains are aligned parallel to each other (interchain bonds). The term pleated sheet arises from the repeated zigzag pattern in the structure (Figure 20.7b). Note how in a pleated sheet structure the amino acid side chains are positioned above and below the plane of the sheet. Very few proteins have entirely a helix or  pleated sheet structures. Instead, most proteins have only certain portions of their molecules in these conformations. The rest of the molecule consists of “unstructured segments.” It is possible to have both a helix and  pleated sheet structures within the same protein. Figure 20.8 is a diagram of a protein chain where both helical and pleated sheet segments, as well as unstructured segments, are present within a single peptide chain. The  pleated sheet segment involves a single peptide chain folding back on itself (intrachain bonds). Helical structure and pleated sheet structure are found only in portions of a protein where the amino acid R groups present are relatively small; large R groups tend to disrupt both of these types of secondary structure. The term unstructured used in describing portions of a protein structure is somewhat of a misnomer, because all molecules of a given protein exhibit identical unstructured segments. An active area of protein research at present involves learning more about the biochemical functions for the unstructured portions of proteins. A growing number of researchers now believe that some “unstructure” is essential to the functioning of many proteins. It confers flexibility to proteins, thereby allowing them to interact with several different substances, an important mechanism for rapid response to changing cellular

R R

R

R

R

R

R R R

Carbon Nitrogen Hydrogen Oxygen

R

R R R

R

R R

R R

R

R group (a)

(b)

Figure 20.7 Two representations of the b pleated sheet protein structure. (a) A representation emphasizing the hydrogen bonds between protein chains. (b) A representation emphasizing the pleats and the location of the R groups.

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Chapter 20 Proteins

Figure 20.8 The secondary structure of a single protein often shows areas of a helix and b pleated sheet configurations, as well as areas of “unstructure.”

 Pleated sheet

 Helix

“Unstructured segment”  Helix

conditions. Often unstructured regions of a protein have the flexibility to bind to several different protein partners, allowing the same amino acid sequence to multitask. The act of binding to another protein does bring added structure to the unstructured portion of the protein, but the added structure is lost when the binding interaction ceases.

20.11 TERTIARY STRUCTURE OF PROTEINS Tertiary protein structure is the overall three-dimensional shape of a protein that results from the interactions between amino acid side chains (R groups) that are widely separated from each other within a peptide chain. A good analogy for the relationships among the primary, secondary, and tertiary structures of a protein is that of a telephone cord (Figure 20.9). The primary structure is the long, straight cord. The coiling of the cord into a helical arrangement gives the secondary structure. The supercoiling arrangement the cord adopts after you hang up the receiver is the tertiary structure.

Interactions Responsible for Tertiary Structure Four types of attractive interactions contribute to the tertiary structure of a protein: (1) covalent disulfide bonds, (2) electrostatic attractions (salt bridges), (3) hydrogen bonds, and (4) hydrophobic attractions. All four of these interactions are interactions between amino acid R groups. This is a major distinction between tertiary-structure interactions and secondary-structure interactions. Tertiary-structure interactions involve the R groups of amino acids; secondary-structure interactions involve the peptide linkages between amino acid residues.

Figure 20.9 A telephone cord has three levels of structure. These structural levels are a good analogy for the first three levels of protein structure. 4

*

7 0

8 #

1 5

2

3

6

9

Primary structure

Secondary structure

Tertiary structure

20.11 Tertiary Structure of Proteins

Figure 20.10 Disulfide bonds involving cysteine residues can form in two different ways: (a) between two 9SH groups on the same chain or (b) between two 9SH groups on different chains.

Cysteine is the only a-amino acid that contains a sulfhydryl group ( — SH).

(a) Between two 9SH groups on the same chain

675

(b) Between two 9SH groups on different chains

CH2

SH

CH2

S

CH2

SH

CH2

SH

CH2

S

HS

CH2

CH2

S S

CH2

Disulfide bonds, the strongest of the tertiary-structure interactions, result from the 9SH groups of two cysteine residues reacting with each other to form a covalent disulfide bond (Section 20.5). This type of interaction is the only one of the four tertiary-structure interactions that involves a covalent bond. Disulfide bond formation may involve two cysteine units in the same peptide chain (an intramolecular disulfide bond; see Figure 20.10a) or two cysteine units in different chains (an intermolecular disulfide bond; see Figure 20.10b). Figure 20.11 gives the structure of the protein hormone insulin, a protein that has two peptide chains and a total of 51 amino acid residues; both inter- and intramolecular disulfide bonds are present in its structure. Electrostatic interactions, also called salt bridges, always involve the interaction between an acidic side chain (R group) and a basic side chain (R group). The side chains of acidic and basic amino acids, at the appropriate pH, carry charges, with the acidic side chain being negatively charged and the basic side chain being positively charged. Such side chain charges occur when a — COOH group becomes a 9COO group and  when a 9NH2 group becomes a O NH3 group. The interaction that occurs between the two types of side chains is a positive–negative ion–ion attraction. Figure 20.12b shows an electrostatic interaction. Hydrogen bonds can occur between amino acids with polar R groups. A variety of polar side chains can be involved, especially those that possess the following functional groups: OOH

O B O C O OH

O NH2

O B O C O NH2

Hydrogen bonds are relatively weak and are easily disrupted by changes in pH and temperature. Figure 20.12c shows the hydrogen-bonding interactions between the R groups of glutamine and serine. Figure 20.11 Human insulin, a small two-chain protein, has both intrachain and interchain disulfide linkages as part of its tertiary structure.

Chain B +

1 Phe Val Chain A Asn H3N

+

H3N 1 Gly Ile

5 Gln His

10 Leu Cys Gly Ser His Leu

Val Glu

5 Val Glu Gln Cys Cys Thr 8 Intrachain disulfide Ser 9 linkage IIe Cys 10 Ser Leu Tyr

Ala Leu Tyr 15 Leu Val

20 25 Cys Gly Glu Arg Gly Phe Phe Tyr Thr

Interchain disulfide linkage Gln Leu Glu Asn Tyr Cys Asn COO– 15 20

COO– 30 Thr Lys Pro

2880T_ch20_655-697.indd Page 676 10/16/08 9:12:11 PM user-s131 /Volumes/MHSF/MH-SANFRAN/MHSF027/MHS...

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Chapter 20 Proteins

Figure 20.12 Four types of interactions between amino acid R groups produce the tertiary structure of a protein. (a) Disulfide bonds. (b) Electrostatic interactions (salt bridges). (c) Hydrogen bonds. (d) Hydrophobic interactions.

CH2 CH2 CH2

S

(a)

␣ Helix

Figure 20.13 A schematic diagram showing the tertiary structure of the single-chain protein myoglobin.

EXAMPLE 20.5 Drawing Structural Representations for Amino Acid Side Chain Interactions Associated with Protein Tertiary Structure

H

+

Cys

NH2

O

–

H3C

Lys

NH3

O

CH3 CH

Ser

(CH2)4

CH2

CH2

(b)

(c)

(d)

Leu

Hydrophobic interactions result when two nonpolar side chains are close to each other. In aqueous solution, many proteins have their polar R groups outward, toward the aqueous solvent (which is also polar), and their nonpolar R groups inward (away from the polar water molecules). The nonpolar R groups then interact with each other. The attractive forces are London forces (Section 7.13) resulting from the momentary uneven distribution of electrons within the side chains. Hydrophobic interactions are common between phenyl rings and alkyl side chains. Although hydrophobic interactions are weaker than hydrogen bonds or electrostatic interactions, they are a significant force in some proteins because there are so many of them; their cumulative effect can be greater in magnitude than the effects of hydrogen bonding. Figure 20.12d shows the hydrophobic interactions between the R groups of phenylalanine and leucine. In 1959, a protein tertiary structure was determined for the first time. The determination involved myoglobin, a conjugated protein (Section 20.8) whose function is oxygen storage in muscle tissue. Figure 20.13 shows myoglobin’s tertiary structure. It involves

Identify the type of noncovalent interaction that occurs between the side chains of the following amino acids and show the interaction using structural representations for the side chains. a. Serine and asparagine b. Glutamic acid and lysine Solution

a. Both serine and asparagine are polar neutral amino acids (see Table 20.1). The side chains of such amino acids interact through hydrogen bonding. A structural representation for this hydrogen bonding interaction is:

..

OCH2O O

H... O

..

D

C O CH2O H2N D

B

+

H3N

Heme

O

Phe

C

C O

S

CH2

COO–

Cys

CH2

Asp

CH2

Gln

Asn

Ser

b. Glutamic acid and lysine have, respectively, acidic and basic side chains (see Table 20.1). Such side chains carry a charge, in solution, as the result of proton transfer. The interaction between the negatively charged acidic side chain and the positively charged basic side chain is an electrostatic interaction. A structural representation for this electrostatic interaction is:

B

O(CH2)2 O C

O⫺ D

Glu

O

⫹

H3NO (CH2)4 O Lys

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

20.12 Quaternary Structure of Proteins

677

Practice Exercise 20.5 Identify the type of noncovalent interaction that occurs between the side chains of the following amino acids and show the interaction using structural representations for the side chains. a. Threonine and asparagine b. Aspartic acid and arginine Answers:

a. Hydrogen bonding;

OH . . . O

CH3 H N D C O CH2O 2

B

D OCHD Thr

Asn

b. Electrostatic interaction;

B

O O



H3ND

C ONHO (CH2)3O

B

OCH2O C

D

HN

Asp

Arg

a single peptide chain of 153 amino acids with numerous a helix segments within the chain. The structure also contains a prosthetic heme group, an iron-containing group with the ability to bind molecular oxygen. A comparison of Figure 20.13 (myoglobin’s tertiary structure) with Figure 20.4 (myoglobin’s primary structure) shows how different the perspectives of primary and tertiary structure are for a protein.

20.12 QUATERNARY STRUCTURE OF PROTEINS Quaternary structure is the highest level of protein organization. It is found only in multimeric proteins (Section 20.8). Such proteins have structures involving two or more peptide chains that are independent of each other — that is, are not covalently bonded to each other. Quaternary protein structure is the organization among the various peptide chains in a multimeric protein. Most multimeric proteins contain an even number of subunits (two subunits  a dimer, four subunits  a tetramer, and so on). The subunits are held together mainly by hydrophobic interactions between amino acid R groups. The noncovalent interactions that contribute to tertiary structure (electrostatic interactions, hydrogen bonds, and hydrophobic interactions) are also responsible for the maintenance of quaternary structure. The noncovalent interactions that contribute to quaternary structure are, however, more easily disrupted. For example, only small changes in cellular conditions can cause a tetrameric protein to fall apart, dissociating into dimers or perhaps four separate subunits, with a resulting temporary loss of protein activity. As original cellular conditions are restored, the tertiary structure automatically re-forms, and normal protein function is restored. An example of a protein with quaternary structure is hemoglobin, the oxygencarrying protein in blood (Figure 20.14). It is a tetramer in which there are two identical a chains and two identical  chains. Each chain enfolds a heme group, the site where oxygen binds to the protein. The Chemistry at a Glance feature on page 678 reviews what we have said about protein structural levels.

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Protein Structure

PRIMARY STRUCTURE

The sequence of amino acids present in a protein’s peptide chain or chains

SECONDARY STRUCTURE

The regularly repeating ordered spatial arrangements of amino acids near each other in the protein chain, which result from hydrogen bonds between carbonyl oxygen atoms and amino hydrogen atoms

Alpha Helix Hydrogen bonds between every fourth amino acid R

Beta Pleated Sheet Hydrogen bonds between two side-by-side chains, or a single chain that is folded back on itself

R

R

R

R

R

R R R

R

R R R

R

R R

R R

TERTIARY STRUCTURE

QUATERNARY STRUCTURE

The overall three-dimensional shape that results from the attractive forces between amino acid side chains (R groups) that are not near each other in the protein chain

The three-dimensional shape of a protein consisting of two or more independent peptide chains, which results from noncovalent interactions between R groups

Figure 20.14 A schematic diagram showing the tertiary and quaternary structure of the oxygen-carrying protein hemoglobin.

Disulfide bonds Electrostatic interactions Hydrogen bonds Hydrophobic interactions

Electrostatic interactions Hydrogen bonds Hydrophobic interactions

␤ Chain

␣ Chain

␤ Chain

␣ Chain Heme group

R

20.13 Protein Classification Based on Shape

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20.13 PROTEIN CLASSIFICATION BASED ON SHAPE Based on molecular shape, which is determined primarily by tertiary and quaternary structural features, there are three main types of proteins: fibrous, globular, and membrane. A fibrous protein is a protein whose molecules have an elongated shape with one dimension much longer than the others. Fibrous proteins tend to have simple, regular, linear structures. There is a tendency for such proteins to aggregate together to form macromolecular structures. A globular protein is a protein whose molecules have peptide chains that are folded into spherical or globular shapes. The folding in such proteins is such that most of the amino acids with hydrophobic side chains (nonpolar R groups) are in the interior of the molecule and most of the hydrophilic side chains (polar R groups) are on the outside of the molecule. Generally, globular proteins are water-soluble substances. A membrane protein is a protein that is found associated with a membrane system of a cell. Membrane protein structure is somewhat opposite that of globular proteins, with most of the hydrophobic amino acid side chains oriented outward. Thus, such proteins tend to be waterinsoluble and they usually have fewer hydrophobic amino acids than globular proteins. Further discussion of proteins in this section is limited to fibrous and globular proteins, as membrane proteins were considered in the previous chapter in relation to cell membrane structure (Section 19.10). Table 20.4 gives examples of selected fibrous and globular proteins. Comparison of fibrous and globular proteins in terms of general properties shows the following differences. 1. Fibrous proteins are generally water-insoluble, whereas globular proteins dissolve in water. This enables globular proteins to travel through the blood and other body fluids to sites where their activity is needed. 2. Fibrous proteins usually have a single type of secondary structure, whereas globular proteins often contain several types of secondary structure. 3. Fibrous proteins generally have structural functions that provide support and external protection, whereas globular proteins are involved in metabolic chemistry, performing functions such as catalysis, transport, and regulation. 4. The number of different kinds of globular protein far exceeds the number of different kinds of fibrous protein. However, because the most abundant proteins in the human body are fibrous proteins rather than globular proteins, the total mass of fibrous proteins present exceeds the total mass of globular proteins present. We will now more closely examine the characteristics of two fibrous proteins (a keratin and collagen) and two globular proteins (hemoglobin and myoglobin) as representatives of their types.

TABLE 20.4 Some Common Fibrous and Globular Proteins

Name

Occurrence and Function

Fibrous proteins (insoluble)

keratins collagens elastins myosins fibrin

found in wool, feathers, hooves, silk, and fingernails found in tendons, bone, and other connective tissue found in blood vessels and ligaments found in muscle tissue found in blood clots

Globular proteins (soluble)

insulin myoglobin hemoglobin transferrin immunoglobulins

regulatory hormone for controlling glucose metabolism involved in oxygen storage in muscles involved in oxygen transport in blood involved in iron transport in blood involved in immune system responses

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␣ Keratin

Figure 20.15 The tail feathers of a peacock contain the fibrous protein a keratin. Natural silk (silkworm silk) and spider silk (spider webs) are made of fibroin, a fibrous protein that exists mainly in a beta pleated sheet form. The great strength and toughness of silk fibers, which exceed those of many synthetic fibers, is related to the close stacking of the beta sheets. A high percentage of the amino acid residues (primary structure) in silk are either glycine (R ⫽ H) or alanine (R ⫽ CH3). It is the smallness of these two R groups that makes the close stacking possible.

Collagen, pronounced “KAHL-uhjen,” is the most abundant protein in the human body.

The fibrous protein ␣ keratin is particularly abundant in nature, where it is found in protective coatings for organisms. It is the major protein constituent of hair, feathers (Figure 20.15), wool, fingernails and toenails, claws, scales, horns, turtle shells, quills, and hooves. The structure of a typical ␣ keratin, that of hair, is depicted in Figure 20.16. The individual molecules are almost wholly ␣ helical (Figure 20.16a). Pairs of these helices twine about one another to produce a coiled coil (Figure 20.16b). In hair, two of the coiled coils then further twist together to form a protofilament (Figure 20.16c). Protofilaments then coil together in groups of four to form microfilaments (Figure 20.16d), which become the “core” unit in the structure of the ␣ keratin of hair. These microfilaments in turn coil at even higher levels. This coiling at higher and higher levels is what produces the strength associated with ␣-keratin-containing proteins. All levels of coiling organization are stabilized by attractive forces of the types previously considered in the discussion of generalized secondary and tertiary protein structure (Sections 20.10 and 20.11). Particularly important are intercoil disulfide bridges that form between cysteine residues. Introduction of disulfide bridges within the several levels of coiling structure determines the “hardness” of an ␣ keratin. “Hard” keratins, such as those found in horns and nails, have considerably more disulfide bridges than their softer counterparts found in hair, wool, and feathers.

Collagen Collagen, the most abundant of all proteins in humans (30% of total body protein), is a major structural material in tendons, ligaments, blood vessels, and skin; it is also the organic component of bones and teeth. Table 20.5 gives the collagen content of selected body tissues. The predominant structural feature within collagen molecules is a triple helix formed when three chains of amino acids wrap around each other to give a ropelike arrangement of polypeptide chains (see Figure 20.17). The rich content of the amino acid proline (up to 20%) in collagen is one reason why it has a triple-helix conformation rather than the simpler ␣ helix structure (Section 20.10). Proline amino acid residues do not fit into regular ␣ helices because of the cyclic nature of the side chain present and its accompanying different “geometry.” H O O H O B B A B A ONO CHOCON CHOCONOCHOCO A A R R CH2 CH2 CH2 Portion of a collagen chain

Figure 20.16 The coiled-coil structure of the fibrous protein a keratin.

(a) ␣ Helix

(b) Coiled coil of two ␣ helices

(c) Protofilament (pair of coiled coils)

(d) Microfilament (four coiled protofilaments)

20.13 Protein Classification Based on Shape

Figure 20.17 A schematic diagram emphasizing how three helical polypeptide chains intertwine to form a triple helix. The chains are partially unwound and cut away to show their structure.

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Polypeptide chains Helical polypeptide chain

TABLE 20.5 The Collagen Content of Selected Body Tissues

Tissue

Achilles tendon aorta bone (mineral-free) cartilage cornea ligament skin

Collagen (% dry mass)

86 12–24 88 46–63 68 17 72

The hemoglobin of a fetus is slightly different in structure from adult hemoglobin. Called fetal hemoglobin, this hemoglobin has a greater affinity for oxygen than the mother’s hemoglobin. This ensures a steady flow of oxygen to the fetus. Shortly after birth, a baby’s body ceases to produce fetal hemoglobin, and its production of “adult” hemoglobin begins.

Collagen molecules (triple helices) are very long, thin, and rigid. Many such molecules, lined up alongside each other, combine to make collagen fibrils. Cross-linking between helices gives the fibrils extra strength. The greater the number of cross links, the more rigid the fibril is. The stiffening of skin and other tissues associated with aging is thought to result, at least in part, from an increasing amount of cross-linking between collagen molecules. The process of tanning, which converts animal hides to leather, involves increasing the degree of cross-linking. Figure 20.18 shows an electron micrograph of collagen fibers.

Hemoglobin The globular protein hemoglobin transports oxygen from the lungs to tissue. Its tertiary structure was shown in Figure 20.14. It is a tetramer (four peptide chains) with each subunit also containing a heme group, the entity that binds oxygen. With four heme groups present, a hemoglobin molecule can transport four oxygen molecules at the same time. The structure of a heme group is H3C H 3C

OOC

CH2 ⫺

OOC

CH2

Fe2⫹ N N

CH2 CH2

CH2 CH3

N N

⫺

CH

CH

CH2

CH3

Heme

It is the iron atom at the center of the heme molecule that actually interacts with the O2.

Myoglobin

Figure 20.18 Electron micrograph of collagen fibers.

The function of hemoglobin is oxygen transfer, and the function of myoglobin is oxygen storage.

The globular protein myoglobin functions as an oxygen storage molecule in muscles. Its tertiary structure was shown in Figure 20.13. Myoglobin is a monomer, whereas hemoglobin is a tetramer. That is, myoglobin consists of a single peptide chain and a heme unit, and hemoglobin has four peptide chains and four heme units. Thus only one O2 molecule can be carried by a myoglobin molecule. The tertiary structure of the single peptide chain of myoglobin is almost identical to the tertiary structure of each of the subunits of hemoglobin. Myoglobin has a higher affinity for oxygen than does hemoglobin. Thus the transfer of oxygen from hemoglobin to myoglobin occurs readily. Oxygen stored in myoglobin molecules serves as a reserve oxygen source for working muscles when their demand for oxygen exceeds that which can be supplied by hemoglobin. The Chemical Connections feature on page 682 considers how the amount of myoglobin present in muscle tissue is related to the color of the meats that humans eat.

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Protein Structure and the Color of Meat

The meat that humans eat is composed primarily of muscle tissue. The major proteins present in such muscle tissue are myosin and actin, which lie in alternating layers and which slide past each other during muscle contraction. Contraction is temporarily maintained through interactions between these two types of proteins. Structurally, myosin consists of a rodlike coil of two alpha helices (fibrous protein) with two globular protein heads. It is the “head portions” of myosin that interact with the actin. Myosin tail

Myosin head

Structurally, actin has the appearance of two filaments spiraling about one another (see diagram below). Each circle in this structural diagram represents a monomeric unit of actin (called globular actin). The monomeric actin units associate to form a long polymer (called fibrous actin). Each identical monomeric actin unit is a globular protein containing many amino acid residues. The chemical process associated with muscle contraction (interaction between myosin and actin) requires molecular oxygen. The oxygen storage protein myoglobin (Section 20.13) is the oxygen source. The amount of myoglobin present in a

muscle is determined by how the muscle is used. Heavily used muscles require larger amounts of myoglobin than infrequently used muscles require. The amount of myoglobin present in muscle tissue is a major determiner of the color of the muscle tissue. Myoglobin molecules have a red color when oxygenated and a purple color when deoxygenated. Thus, heavily worked muscles have a darker color than infrequently used muscles. The different colors of meat reflect the concentration of myoglobin in the muscle tissue. In turkeys and chickens, which walk around a lot but rarely fly, the leg meat is dark, the breast meat is white. On the other hand, game birds that do fly a lot have dark breast meat. In general, game animals (which use all of their muscles regularly) tend to have darker meat than domesticated animals. All land animals and birds need to support their own weight. Fish, on the other hand, are supported by water as they swim, which reduces the need for myoglobin oxygen support. Hence fish tend to have lighter flesh. Fish that spend most of their time lying at the bottom of a body of water have the lightest (whitest) flesh of all. Salmon flesh contains additional pigments that give it its characteristic “orange-pink” color. Meat, when cooked, turns brown as the result of changes in myoglobin structure caused by the heat; the iron atom in the heme unit of myoglobin (Section 20.13) becomes oxidized. When meat is heavily salted with preservatives (NaCl, NaNO2, or the like), as in the preparation of ham, the myoglobin picks up nitrite ions, and its color changes to pink.

20.14 PROTEIN CLASSIFICATION BASED ON FUNCTION Proteins play crucial roles in almost all biochemical processes. The diversity of functions exhibited by proteins far exceeds that of other major types of biochemical molecules. The functional versatility of proteins stems from (1) their ability to bind small molecules specifically and strongly to themselves, (2) their ability to bind other proteins, often other like proteins, to form fiber-like structures, and (3) their ability to bind to, and often become integrated into, cell membranes. The following list gives a number of the major categories of proteins based on function. The order is not to be taken as an indication of relative functional importance. The list is also to be considered a selective list with a number of functions not included because of space considerations. 1. Catalytic proteins. Proteins are probably best known for their role as catalysts. Proteins with the role of biochemical catalyst are called enzymes. An entire chapter in this text, Chapter 21, is devoted to this most important role for proteins. Enzymes participate in almost all of the metabolic reactions that occur in cells. The chemistry of human genetics, to be discussed in detail in Chapter 22, is very dependent on the presence of enzymes.

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

20.15 Protein Hydrolysis

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2. Defense proteins. These proteins, also called immunoglobulins or antibodies (Section 20.17), are central to the functioning of the body’s immune system. They bind to foreign substances, such as bacteria and viruses, to help combat invasion of the body by foreign particles. 3. Transport proteins. These proteins bind to particular small biomolecules and transport them to other locations in the body and then release the small molecules as needed at the destination location. The most well-known example of a transport protein is hemoglobin (Section 20.12), which carries oxygen from the lungs to other organs and tissues. Another transport protein is transferrin, which carries iron from the liver to the bone marrow. High- and low-density lipoproteins (Section 20.18) are carriers of cholesterol in the bloodstream. 4. Messenger proteins. These proteins transmit signals to coordinate biochemical processes between different cells, tissues, and organs. A number of hormones (Section 19.12) that regulate body processes are messenger proteins, including insulin and glucagon (Section 24.9). Human growth hormone is another example of a messenger protein. 5. Contractile proteins. These proteins are necessary for all forms of movement. Muscles are composed of filament-like contractile proteins that, in response to nerve stimuli, undergo conformation changes that involve contraction and extension. Actin and myosin (Section 20.13) are examples of such proteins. Human reproduction depends on the movement of sperm. Sperm can “swim” because of long flagella made up of contractile proteins. 6. Structural proteins. These proteins confer stiffness and rigidity to otherwise fluidlike biochemical systems. Collagen (Section 20.13) is a component of cartilage and a keratin (Section 20.13) gives mechanical strength as well as protective covering to hair, fingernails, feathers, hooves, and some animal shells. 7. Transmembrane proteins. These proteins, which span a cell membrane (Section 19.10) help control the movement of small molecules and ions through the cell membrane. Many such proteins have channels through which molecules can enter and exit a cell. Such protein channels are very selective, often allowing passage to just one type of molecule or ion. 8. Storage proteins. These proteins bind (and store) small molecules for future use. During degradation of hemoglobin (Section 26.7) the iron atoms present are released and become part of ferritin, an iron-storage protein, which saves the iron for use in the biosynthesis of new hemoglobin molecules. Myoglobin (Section 20.13) is an oxygen-storage protein present in muscle; the oxygen so stored is a reserve oxygen source for working muscle. 9. Regulatory proteins. These proteins are often found “embedded” in the exterior surface of cell membranes. They act as sites at which messenger molecules, including messenger proteins such as insulin, can bind and thereby initiate the effect that the messenger “carries.” Regulatory proteins are often the molecules that bind to enzymes (catalytic proteins), thereby turning them “on” and “off,” and thus controlling enzymatic action (Section 21.8). 10. Nutrient proteins. These proteins are particularly important in the early stages of life, from embryo to infant. Casein, found in milk, and ovalbumin, found in egg white, are two examples of such proteins. The role of milk in nature is to nourish and provide immunological protection for mammalian young. Three-fourths of the protein in milk is casein. Over 50% of the protein in egg white is ovalbumin.

20.15 PROTEIN HYDROLYSIS When a protein or smaller peptide in a solution of strong acid or strong base is heated, the peptide bonds of the amino acid chain are hydrolyzed and free amino acids are produced. The hydrolysis reaction is the reverse of the formation reaction for a peptide bond. Amine and carboxylic acid functional groups are regenerated.

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Let us consider the hydrolysis of the tripeptide Ala–Gly–Cys under acidic conditions. Complete hydrolysis produces one unit each of the amino acids alanine, glycine, and cysteine. The equation for the hydrolysis is H O H H O H H A B A A B A A H3NO COCONO CO CONO COCOOH A A A H CH3 CH2 A SH ⫹

H2O, H⫹ heat

Ala᎐Gly᎐Cys

Protein hydrolysis produces free amino acids. This process is the reverse of protein synthesis, where free amino acids are combined.

H H H A A A ⫹ ⫹ H3NOCO COOH ⫹ H3NO COCOOH ⫹ H3NO COCOOH A A A CH3 H CH2 A SH ⫹

Ala

Gly

Cys

Note that the product amino acids in this reaction are written in positive-ion form because of the acidic reaction conditions. Protein digestion (Section 26.1) is simply enzyme-catalyzed hydrolysis of ingested protein. The free amino acids produced from this process are absorbed through the intestinal wall into the bloodstream and transported to the liver. Here they become the raw materials for the synthesis of new protein. Also, the hydrolysis of cellular proteins to amino acids is an ongoing process, as the body resynthesizes needed molecules and tissue.

20.16 PROTEIN DENATURATION A consequence of protein denaturation, the partial or complete loss of a protein’s three-dimensional structure, is loss of biochemical activity for the protein.

Protein denaturation is the partial or complete disorganization of a protein’s characteristic three-dimensional shape as a result of disruption of its secondary, tertiary, and quaternary structural interactions. Because the biochemical function of a protein depends on its three-dimensional shape, the result of denaturation is loss of biochemical activity. Protein denaturation does not affect the primary structure of a protein. Although some proteins lose all of their three-dimensional structural characteristics upon denaturation (Figure 20.19), most proteins maintain some three-dimensional structure. Often, for limited denaturation changes, it is possible to find conditions under which the effects of denaturation can be reversed; this restoration process, in which the protein is “refolded,” is called renaturation. However, for extensive denaturation changes, the process is usually irreversible. Loss of water solubility is a frequent physical consequence of protein denaturation. The precipitation out of biochemical solution of denatured protein is called coagulation. A most dramatic example of protein denaturation occurs when egg white (a concentrated solution of the protein albumin) is poured onto a hot surface. The clear albumin solution immediately changes into a white solid with a jelly-like consistency (see Figure 20.20). A similar process occurs when hamburger juices encounter a hot surface. A brown jelly-like solid forms.

Figure 20.19 Protein denaturation involves loss of the protein’s threedimensional structure. Complete loss of such structure produces an "unstructured" protein strand.

Denaturation ␣ Helix

“Unstructured” protein strand

20.17 Glycoproteins

Figure 20.20 Heat denatures the protein in egg white, producing a white jellylike solid. The primary structure of the protein remains intact, but all higher levels of protein structure are disrupted.

Globular proteins denature more readily than fibrous proteins because of weaker secondary and tertiary attractive forces.

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When protein-containing foods are cooked, protein denaturation occurs. Such “cooked” protein is more easily digested because it is easier for digestive enzymes to “work on” denatured (unraveled) protein. Cooking foods also kills microorganisms through protein denaturation. For example, ham and bacon can harbor parasites that cause trichinosis. Cooking the ham or bacon denatures parasite protein. In surgery, heat is often used to seal small blood vessels. This process is called cauterization. Small wounds can also be sealed by cauterization. Heat-induced denaturation is used in sterilizing surgical instruments and in canning foods; bacteria are destroyed when the heat denatures their protein. The body temperature of a patient with fever may rise to 102⬚F, 103⬚F, or even 104⬚ without serious consequences. A temperature above 106⬚F (41⬚C) is extremely dangerous, for at this level the enzymes of the body begin to be inactivated. Enzymes, which function as catalysts for almost all body reactions, are protein. Inactivation of enzymes, through denaturation, can have lethal effects on body chemistry. The effect of ultraviolet radiation from the sun, an ionizing radiation (Section 11.7), is similar to that of heat. Denatured skin proteins cause most of the problems associated with sunburn. A curdy precipitate of casein, the principal protein in milk, is formed in the stomach when the hydrochloric acid of gastric juice denatures the casein. The curdling of milk that takes place when milk sours or cheese is made (see Figure 20.21) results from the presence of lactic acid, a by-product of bacterial growth. Yogurt is prepared by growing lactic-acid-producing bacteria in skim milk. The coagulated denatured protein gives yogurt its semi-solid consistency. Serious eye damage can result from eye tissue contact with acids or bases, when irreversibly denatured and coagulated protein causes a clouded cornea. This reaction is part of the basis for the rule that students wear protective eyewear in the chemistry laboratory. Alcohols are an important type of denaturing agent. Denaturation of bacterial protein takes place when isopropyl or ethyl alcohol is used as a disinfectant — hence the common practice of swabbing the skin with alcohol before giving an injection. Interestingly, pure isopropyl or ethyl alcohol is less effective than the commonly used 70% alcohol solution. Pure alcohol quickly denatures and coagulates the bacterial surface, thereby forming an effective barrier to further penetration by the alcohol. The 70% solution denatures more slowly and allows complete penetration to be achieved before coagulation of the surface proteins takes place. The process of giving a person a “hair permanent” involves protein denaturation through the use of reducing agents and oxidizing agents (see the Chemical Connections feature on page 686). Table 20.6 is a listing of selected physical and chemical agents that cause protein denaturation. The effectiveness of a given denaturing agent depends on the type of protein upon which it is acting.

20.17 GLYCOPROTEINS

Figure 20.21 Storage room for cheese; during storage cheese “matures” as bacteria and enzymes ferment the cheese, giving it a stronger flavor.

A glycoprotein is a protein that contains carbohydrates or carbohydrate derivatives in addition to amino acids (Section 18.18). The carbohydrate content of glycoproteins is variable (from a few percent up to 85%), but it is fixed for any specific glycoprotein. Glycoproteins include a number of very important substances; two of these, collagen and immunoglobulins, are considered in this section. Many of the proteins in cell membranes (lipid bilayers; see Section 19.10) are actually glycoproteins. The blood group markers of the ABO system (see the Chemical Connections feature on page 580 in Chapter 18) are also glycoproteins in which the carbohydrate content can reach 85%.

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Denaturation and Human Hair

The process used in waving hair — that is, in a hair permanent — involves reversible denaturation. Hair is protein in which many disulfide ( — S — S — ) linkages occur as part of its tertiary structure; 16%–18% of hair is the amino acid cysteine. It is these disulfide linkages that give hair protein its overall shape. When a permanent is administered, hair is first treated with a reducing agent (ammonium thioglycolate) that breaks the disulfide linkages in the hair, producing two sulfhydryl ( — SH) groups:

Disulfide bridges S

S

S

S

S

Reducing agents

Finally, the reduced and rearranged hair is treated with an oxidizing agent (potassium bromate) to form disulfide linkages at new locations within the hair: Sulfhydryl groups

SH SH

S

S

S

S

S

S

S

S

S

S

S

SH SH

SH SH

S

S

S

S

S

S

S

S

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

SH SH

re-formed disulfide bridges S

SH SH

sulfhydryl groups

SH SH

Oxidizing agents

SH SH

SH SH

SH SH

SH SH

S

S

SH SH

SH SH

SH SH

S S S S

S

S

S

S

S

S

S

S

S

S

S S

S

S S

S

S

The new shape and curl of the hair are maintained by the newly formed disulfide bonds and the resulting new tertiary structure accompanying their formation. Of course, as new hair grows in, the “permanent” process has to be repeated.

The “reduced” hair, whose tertiary structure has been disrupted, is then wound on curlers to give it a new configuration.

TABLE 20.6 Selected Physical and Chemical Denaturing Agents

Disulfide bridges, which involve covalent bonds, impart considerable resistance to denaturation because they are much stronger than the noncovalent interactions otherwise present.

Denaturing Agent

Mode of Action

heat

disrupts hydrogen bonds by making molecules vibrate too violently; produces coagulation, as in the frying of an egg

microwave radiation

causes violent vibrations of molecules that disrupt hydrogen bonds

ultraviolet radiation

operates very similarly to the action of heat (e.g., sunburning)

violent whipping or shaking

causes molecules in globular shapes to extend to longer lengths, which then entangle (e.g., beating egg white into meringue)

detergent

affects R-group interactions

organic solvents (e.g., ethanol, 2-propanol, acetone)

interfere with R-group interactions because these solvents also can form hydrogen bonds; quickly denature proteins in bacteria, killing them (e.g., the disinfectant action of 70% ethanol)

strong acids and bases

disrupt hydrogen bonds and salt bridges; prolonged action leads to actual hydrolysis of peptide bonds

salts of heavy metals (e.g., salts of Hg2, Ag, Pb2)

metal ions combine with 9SH groups and form poisonous salts

reducing agents

reduce disulfide linkages to produce 9SH groups

20.17 Glycoproteins

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Collagen Nonstandard amino acids consist of amino acid residues that have been chemically modified after their incorporation into a protein (as is the case with 4-hydroxyproline and 5-hydroxylysine) and amino acids that occur in living organisms but are not found in proteins.

The fibrous protein collagen, whose structure was first considered in Section 20.13, qualifies as a glycoprotein because carbohydrate units are present in its structure. This structural feature of collagen, not considered previously, involves the presence of the nonstandard amino acids 4-hydroxyproline (5%) and 5-hydroxylysine (1%) — derivatives of the standard amino acids proline and lysine (Table 20.1). ⫹

H2N

O B CHO COO⫺

CH2 CH2 CHO OH 4-Hydroxyproline

A primary biochemical function of vitamin C involves the hydroxylation of proline and lysine during collagen formation. These hydroxylation processes require the enzymes proline hydroxylase and lysine hydroxylase. These enzymes can function only in the presence of vitamin C.

O B H3NO CHO COO⫺ A CH2 A CH2 A CHO OH A CH2 A ⫹ NH3 ⫹

5-Hydroxylysine

The presence of carbohydrate units (mostly glucose, galactose, and their disaccharides) attached by glycosidic linkages (Section 18.13) to collagen at its 5-hydroxylysine residues causes collagen to be classified as a glycoprotein. The function of the carbohydrate groups in collagen is related to cross-linking; they direct the assembly of collagen triple helices into more complex aggregations called collagen fibrils. When collagen is boiled in water, under basic conditions, it is converted to the water-soluble protein gelatin. This process involves both denaturation (Section 20.15) and hydrolysis (Section 20.14). Heat acts as a denaturant, causing rupture of the hydrogen bonds supporting collagen’s triple-helix structure. Regions in the amino acid chains where proline and hydroxyproline concentrations are high are particularly susceptible to hydrolysis, which breaks up the polypeptide chains. Meats become more tender when cooked because of the conversion of some collagen to gelatin. Tougher cuts of meat (more cross-linking), such as stew meat, need longer cooking times.

Immunoglobulins Immunoglobulins are among the most important and interesting of the soluble proteins in the human body. An immunoglobulin is a glycoprotein produced by an organism as a protective response to the invasion of microorganisms or foreign molecules. Different classes of immunoglobulins, identified by differing carbohydrate content and molecular mass, exist. Immunoglobulins serve as antibodies to combat invasion of the body by antigens. An antigen is a foreign substance, such as a bacterium or virus, that invades the human body. An antibody is a biochemical molecule that counteracts a specific antigen. The immune system of the human body has the capability to produce immunoglobulins that respond to several million different antigens. All types of immunoglobulin molecules have much the same basic structure, which includes the following features: 1. Four polypeptide chains are present: two identical heavy (H) chains and two identical light (L) chains. 2. The H chains, which usually contain 400–500 amino acid residues, are approximately twice as long as the L chains. 3. Both the H and L chains have constant and variable regions. The constant regions have the same amino acid sequence from immunoglobulin to immunoglobulin, and the variable regions have a different amino acid sequence in each immunoglobulin. 4. The carbohydrate content of various immunoglobulins varies from 1% to 12% by mass.

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Cyclosporine: An Antirejection Drug

The following diagram shows the amino acid sequence within the cyclosporine ring. Seven of the amino acid units,

Val*

10

11

R* = 7C

R = ethyl

1

2

8

7

6

5

3 4

Ala

Ala

Leu*

Val

Leu*

y*

OCHO CHO CH2 O CHPCHOCH3 A A OH CH3

u* Le 9

Leu*

Gl

The survival rate for patients undergoing human organ transplant operations such as heart, liver, or kidney replacement has risen dramatically since the late 1980s. This increased success coincides with the introduction of new drugs for controlling transplant rejection by a patient’s own immune system. One of the best known of these immunosuppressive agents (antirejection drugs) is cyclosporine, a substance obtained from a particular type of soil fungus. The primary structure of cyclosporine is that of a cyclic peptide containing 11 amino acid units. Ten of these are amino acids, which have simple side chains (four or fewer carbon atoms). The eleventh amino acid, which is the key to cyclosporine’s pharmacological activity, is very unusual, having not been previously encountered. It has a 7-carbon branched, unsaturated, hydroxylated side chain with the structure

denoted by asterisks, have their nitrogen atom methylated; that is, a methyl group has replaced the hydrogen atom. This unique structural feature makes cyclosporine water-insoluble but fat-soluble. The fat solubility of cyclosporine allows it to cross cell membranes readily and to be widely distributed in the body. It is administered either intravenously or orally. Because of its low water solubility, the drug is supplied in olive oil for oral administration. Cyclosporine has a narrow therapeutic index. When the blood concentration is too low, inadequate immunosuppression occurs. On the other hand, a high cyclosporine concentration can lead to kidney problems.

5. The secondary and tertiary structures are similar for all immunoglobulins. They involve a Y-shaped conformation (Figure 20.22) with disulfide linkages between H and L chains stabilizing the structure. The interaction of an immunoglobulin molecule with an antigen occurs at the “tips” (uppermost part) of the Y structure. These tips are the variable-composition region of the immunoglobulin structure. It is here that the antigen binds specifically, and it is here that the amino acid sequence differs from one immunoglobulin to another. Each immunoglobulin has two identical active sites and can thus bind to two molecules of the antigen it is “designed for.” The action of many such immunoglobulins of a given type in concert with each other creates an antigen–antibody complex

Figure 20.22 This schematic diagram shows the structure of an immunoglobulin. Two heavy (H) polypeptide chains and two light (L) polypeptide chains are cross-linked by disulfide bridges. The purple areas are the constant amino acid regions, and the areas shown in red are the variable amino acid regions of each chain. Carbohydrate molecules attached to the heavy chains aid in determining the destinations of immunoglobulins in the tissues.

Antigen binding site

Amino end

Amino end

H

Antigen binding site

H Amino end

Amino end

L

S

S

S

Carboxyl end

S S S S

Carboxyl ends

S

Carboxyl end

L

20.18 Lipoproteins

689

Figure 20.23 In this immunoglobulin–antigen complex, note that more than one immunoglobulin molecule can attach itself to a given antigen. Also, any given immunoglobulin has only two sites where antigen can bind.

Antigen

Immunoglobin molecule

that precipitates from solution (Figure 20.23). Eventually, an invading antigen can be eliminated from the body through such precipitation. The bonding of an antigen to the variable region of an immunoglobulin occurs through hydrophobic interactions, dipole– dipole interactions, and hydrogen bonds rather than covalent bonds. The importance of immunoglobulins is amply and tragically demonstrated by the effects of AIDS (acquired immunodeficiency syndrome). The AIDS virus upsets the body’s normal production of immunoglobulins and leaves the body susceptible to what would otherwise not be debilitating and deadly infections. Individuals who receive organ transplants must be given drugs to suppress the production of immunoglobulins against foreign proteins in the new organ, thus preventing rejection of the organ. The major reason for the increasing importance of organ transplants is the successful development of drugs that can properly manipulate the body’s immune system (see the Chemical Connections feature on cyclosporine on page 688). Many reasons exist for a mother to breast-feed a newborn infant. One of the most important is immunoglobulins. During the first two or three days of lactation, the breasts produce colostrum, a premilk substance containing immunoglobulins from the mother’s blood. Colostrum helps protect the newborn infant from those infections to which the mother has developed immunity. These diseases are the ones in her environment — precisely those the infant needs protection from. Breast milk, once it is produced, is a source of immunoglobulins for the infant for a short time. (After the first week of nursing, immunoglobulin concentrations in the milk decrease rapidly.) Infant formula used as a substitute for breast milk is almost always nutritionally equivalent, but it does not contain immunoglobulins.

20.18 LIPOPROTEINS A lipoprotein is a conjugated protein that contains lipids in addition to amino acids. The major function of such proteins is to help suspend lipids and transport them through the bloodstream. Lipids, in general, are insoluble in blood (an aqueous medium) because of their nonpolar nature (Section 19.1). A plasma lipoprotein is a lipoprotein that is involved in the transport system for lipids in the bloodstream. These proteins have a spherical structure that involves a central core of lipid material (triacylglycerols and cholesterol esters) surrounded by a shell (membrane structure) of phospholipids, cholesterol, and proteins. In the blood, cholesterol exists primarily in the form of cholesterol esters formed from the esterification of cholesterol’s hydroxyl group with a fatty acid.

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Chapter 20 Proteins

O B D COO Fatty acid

Ester linkage

Cholesterol

Figure 20.24 is a depiction of such a spherical lipoprotein structure. There are four major classes of plasma lipoproteins: 1. Chylomicrons. Their function is to transport dietary triacylglycerols from the intestine to the liver and to adipose tissue. 2. Very-low-density lipoproteins (VLDL). Their function is to transport triacylglycerols synthesized in the liver to adipose tissue. 3. Low-density lipoproteins (LDL). Their function is to transport cholesterol synthesized in the liver to cells throughout the body. 4. High-density lipoproteins (HDL). Their function is to collect excess cholesterol from body tissues and transport it back to the liver for degradation to bile acids.

c

HEMICAL

onnections

Lipoproteins and Heart Disease Risk

In the United States, heart disease is the number-one health problem for both men and women. There are many risk factors associated with heart disease, some of which are controllable and some of which are not. You can’t change your age, race, or family history (genetics). But you can control (manage) factors such as your weight, whether or not you smoke, and your cholesterol level. Relative to high cholesterol as a risk factor for heart disease, studies now indicate that just focusing on the numerical value of cholesterol present in the blood is an oversimplification of the problem. Consideration of the “form” in which the cholesterol is present is as important as the total amount. Much of the research concerning the “form” of cholesterol present relates to the lipoproteins LDL and HDL present in the blood. Both LDLs and HDLs are involved in cholesterol transport (Section 20.18). LDLs carry approximately 80% of the cholesterol and HDLs the remainder. Of significance, LDLs and HDLs carry cholesterol for different purposes. LDLs carry cholesterol to cells for their use, whereas HDLs carry excess cholesterol away from cells to the liver for processing and excretion from the body. Studies show that LDL levels correlate directly with heart disease, whereas HDL levels correlate inversely with heart disease risk. Thus HDL is sometimes referred to as “good” cholesterol (HDL  Healthy) and LDL as “bad” cholesterol (LDL  Less healthy). The goal of dietary measures to slow the advance of atherosclerosis is to reduce LDL cholesterol levels. Reduction in the dietary intake of saturated fat appears to be a key action (Section 19.5). High HDL levels are desirable because they give the body an efficient means of removing excess cholesterol. Low HDL

levels can result in excess cholesterol depositing within the circulatory system. In general, women have higher HDL levels than men — an average of 55 mg per 100 mL of blood serum versus 45 mg per 100 mL. This may explain in part why proportionately fewer women have heart attacks than men. Nonsmokers have uniformly higher HDL levels than smokers. Exercise on a regular basis tends to increase HDL levels. This discovery has increased the popularity of walking and running exercise. Genetics also plays a role in establishing HDL as well as other lipoprotein concentrations in the blood. A person’s total blood cholesterol level does not necessarily correlate with that individual’s real risk for heart and blood vessel disease. A better measure is the cholesterol ratio, which is defined as Cholesterol ratio 

total cholesterol HDL cholesterol

For example, if a person’s total cholesterol is 200 and his or her HDL is 45, then the cholesterol ratio would be 4.4. According to the accompanying guidelines for interpreting cholesterol ratio values, this indicates an average risk for heart disease. What Your Cholesterol Ratio Means Ratio 6.0 5.0 4.5 4.0 3.0

Heart Disease Risk high above average average below average low

2880T_ch20_655-697.indd Page 691 10/16/08 9:16:21 PM user-s131 /Volumes/MHSF/MH-SANFRAN/MHSF027/MHS...

20.18 Lipoproteins

691

Figure 20.24 A model for the structure of a plasma lipoprotein.

Cholesterol Cholesterol esters Protein

Triacylglycerols

Phospholipid

The density of a lipoprotein is related to the fractions of protein and lipid material present. The greater the amount of protein in the lipoprotein, the higher the density. Figure 20.25 characterizes the major plasma lipoprotein types in terms of density as well as lipid–protein composition. The presence or absence of various types of lipoproteins in the blood appears to have implications for the health of the heart and blood vessels. Lipoprotein levels in the blood are now used as an indicator of heart disease risk (see the Chemical Connections feature on page 689). Figure 20.25 Densities and relative amounts of proteins, phospholipids, cholesterol, and triacylglycerols present in the four major classes of plasma lipoproteins.

Chylomicron Density = less than 0.95 g/mL

Very-low-density Lipoprotein Density = 0.95 to 1.02 g/mL

Protein 1% Cholesterol 5% Phospholipid 4%

Protein 8% Phospholipid 18%

Cholesterol 14%

Triacylglycerol 90%

Triacylglycerol 60%

Low-density Lipoprotein Density = 1.02 to 1.06 g/mL

High-density Lipoprotein Density = 1.06 to 1.21 g/mL

Phospholipid 20%

Phospholipid 30%

Protein 25% Triacylglycerol 10% Cholesterol 45%

Protein 45% Cholesterol 20%

Triacylglycerol 5%

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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c

O N C E P TS TO R E M E M B E R

k

EY R E A C T I O N S A N D E Q U AT I O N S

Protein. A protein is a polymer in which the monomer units are amino acids (Section 20.1). A-Amino acid. An -amino acid is an amino acid in which the amino group and the carboxyl group are both attached to the -carbon atom (Section 20.2). Standard amino acid. A standard amino acid is one of the 20 -amino acids that are normally present in protein (Section 20.2). Amino acid classifications. Amino acids are classified as nonpolar, polar neutral, polar basic, or polar acidic depending on the nature of the side chain (R group) present (Section 20.2). Chirality of amino acids. Amino acids found in proteins are always left-handed (L isomer) (Section 20.3). Zwitterion. A zwitterion is a molecule that has a positive charge on one atom and a negative charge on another atom. In neutral solution and in the solid state, amino acids exist as zwitterions. For amino acids in solution, the isoelectric point is the pH at which the solution has no net charge because an equal number of positive and negative charges are present (Section 20.4). Disulfide bond formation. The amino acid cysteine readily dimerizes; the 9SH groups of two cysteine molecules interact to form a covalent disulfide bond (Section 20.5). Peptide bond. A peptide bond is an amide bond involving the carboxyl group of one amino acid and the amino group of another amino acid. In a protein, the amino acids are linked to each other through peptide bonds (Section 20.6). Biochemically important peptides. Numerous small peptides are biochemically active. Their functions include hormonal action, neurotransmission functions, and antioxidant activity (Section 20.7). General characteristics of proteins. Proteins are peptides with at least 40 amino acid residues. A single peptide chain is present in a monomeric protein and two or more peptide chains are present in a multimeric protein. A simple protein contains only one or more peptide chains. A conjugated protein contains one or more additional chemical components, called prosthetic groups, in addition to peptide chains (Section 20.8).

1. Formation of a zwitterion at pH 7 (Section 20.4)

H2NOCHO COOH A R

4. Formation of a peptide bond (Section 20.6)

⫹

H3NOCHO COO⫺ A R

2. Conversion of a zwitterion to a positive ion in acidic solution (Section 20.4) ⫹

H3NOCHO COO⫺ ⫹ H3O⫹ A R

⫹

H3NOCHO COOH ⫹ H2O A R

3. Conversion of a zwitterion to a negative ion in basic solution (Section 20.4) ⫹

⫺

⫺

H3NOCHO COO ⫹ OH A R

Primary protein structure. The primary structure of a protein is the sequence of amino acids present in the peptide chain or chains of the protein (Section 20.9). Secondary protein structure. The secondary structure of a protein is the arrangement in space of the backbone portion of the protein. The two major types of protein secondary structure are the a helix and the  pleated sheet (Section 20.10). Tertiary protein structure. The tertiary structure of a protein is the overall three-dimensional shape that results from the attractive forces among amino acid side chains (R groups) (Section 20.11). Quaternary protein structure. The quaternary structure of a protein involves the associations among the peptide chains present in a multimeric protein (Section 20.12). Fibrous and globular proteins. Fibrous proteins are generally insoluble in water and have a long, thin, fibrous shape.  Keratin and collagen are important fibrous proteins. Globular proteins are generally soluble in water and have a roughly spherical or globular overall shape. Hemoglobin and myoglobin are important globular proteins (Section 20.13). Protein hydrolysis. Protein hydrolysis is a chemical reaction in which peptide bonds within a protein are broken through reaction with water. Complete hydrolysis produces free amino acids (Section 20.15). Protein denaturation. Protein denaturation is the partial or complete disorganization of a protein’s characteristic three-dimensional shape as a result of disruption of its secondary, tertiary, and quaternary structural interactions (Section 20.16). Glycoproteins. Glycoproteins are conjugated proteins that contain carbohydrates or carbohydrate derivatives in addition to amino acids. Collagen and immunoglobulins are important glycoproteins (Section 20.17). Lipoproteins. Lipoproteins are conjugated proteins that are composed of both lipids and amino acids. Lipoproteins are classified on the basis of their density (Section 20.18).

⫺

H2NOCHO COO ⫹ H2O A R

⫹

⫹

H 3NOCHOCOO ⫺ ⫹ H 3N OCHO COO ⫺ A A R R⬘

O H B A H3NOCHO CONOCHO COO ⫺ ⫹ H2O A A R R⬘ 5. Hydrolysis of a protein in acidic solution (Section 20.15) ⫹

H⫹

H⫹

Protein ⫹ H2O ¡ smaller peptides ¡ amino acids 6. Denaturation of a protein (Section 20.16) Protein with 1°, 2°, and 3° structure

Denaturing

88888888n agent

Protein with 1° structure only

Exercises and Problems

693

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Characteristics of Proteins (Section 20.1) 20.1 What is the general name for the building blocks (monomers) from which a protein (polymer) is made? 20.2 What element is always present in proteins that is seldom present in carbohydrates and lipids? 20.3 What percent of a cell’s overall mass is accounted for by proteins? 20.4 Approximately how many different proteins are present in a

typical human cell?

20.18 What are the three-letter abbreviations for the three polar basic

amino acids?

20.19 Classify each of the following amino acids as nonpolar, polar

neutral, polar acidic, or polar basic. a. Asn b. Glu c. Pro d. Ser 20.20 Classify each of the following amino acids as nonpolar, polar neutral, polar acidic, or polar basic. a. Gly b. Thr c. Tyr d. His Chirality and Amino Acids (Section 20.3)

Amino Acid Structural Characteristics (Section 20.2) 20.5 Which of the following structures represent ␣-amino acids? H H COOH a. b. A A A H2NO C O CH2 H2NOC O COOH A A CH3 CH3 c.

H d. H A A H2NOC O COOH H2NOCH2 OC O COOH A A CH2 H A CH3

20.6 What is the significance of the prefix ␣ in the designation

␣-amino acid?

20.7 What is the major structural difference among the various

standard amino acids?

20.8 On the basis of polarity, what are the four types of side chains

found in the standard amino acids?

20.9 With the help of Table 20.1, determine which of the standard

amino acids have a side chain with the following characteristics. a. Contains an aromatic group b. Contains the element sulfur c. Contains a carboxyl group d. Contains a hydroxyl group 20.10 With the help of Table 20.1, determine which of the standard amino acids have a side chain with the following characteristics. a. Contains only carbon and hydrogen b. Contains an amino group c. Contains an amide group d. Contains more than four carbon atoms 20.11 What is the distinguishing characteristic of a polar basic amino

acid? 20.12 What is the distinguishing characteristic of a polar acidic amino acid?

20.21 To which family of mirror-image isomers do nearly all naturally

occurring amino acids belong?

20.22 In what way is the structure of glycine different from that of the

other 19 common amino acids?

20.23 Draw Fischer projection formulas for the following amino acids.

b. D-Serine a. L-Serine d. L-Leucine c. D-Alanine 20.24 Draw Fischer projection formulas for the following amino acids. b. D-Cysteine a. L-Cysteine d. L-Valine c. D-Alanine Acid–Base Properties of Amino Acids (Section 20.4)

20.25 At room temperature, amino acids are solids with relatively

high decomposition points. Explain why.

20.26 Amino acids exist as zwitterions in the solid state. Explain why. 20.27 Draw the zwitterion structure for each of the following amino

acids. a. Leucine b. Isoleucine c. Cysteine d. Glycine 20.28 Draw the zwitterion structure for each of the following amino acids. a. Serine b. Methionine c. Threonine d. Phenylalanine 20.29 Draw the structure of serine at each of the following pH values.

a. 5.68

b. 1.0

c. 12.0

d. 3.0

20.30 Draw the structure of glycine at each of the following pH

values. a. 5.97

b. 13.0

c. 2.0

d. 11.0

20.31 Explain what is meant by the term isoelectric point. 20.32 Most amino acids have isoelectric points between 5.0 and 6.0,

but the isoelectric point of lysine is 9.7. Explain why lysine has such a high value for its isoelectric point.

20.33 Glutamic acid exists in two low-pH forms instead of the usual

from that of the other 19 standard amino acids? 20.14 Which two of the standard amino acids are constitutional isomers?

one. Explain why. 20.34 Arginine exists in two high-pH forms instead of the usual one. Explain why.

20.15 What amino acids do these abbreviations stand for?

20.35 Predict the direction of movement of each of the following

20.13 In what way is the structure of the amino acid proline different

a. Ala b. Leu c. Met d. Trp 20.16 What amino acids do these abbreviations stand for? a. Asp b. Cys c. Phe d. Val 20.17 Which four standard amino acids have three-letter abbreviations

that are not the first three letters of their common names?

amino acids in a solution at the pH value specified under the influence of an electric field. Indicate the direction as toward the positive electrode or toward the negative electrode. Write “isoelectric” if no net movement occurs. a. Alanine at pH ⫽ 12.0 b. Valine at pH ⫽ 5.97 c. Aspartic acid at pH ⫽ 1.0 d. Arginine at pH ⫽ 13.0

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Chapter 20 Proteins

20.36 Predict the direction of movement of each of the following

amino acids in a solution at the pH value specified under the influence of an electric field. Indicate the direction as toward the positive electrode or toward the negative electrode. Write “isoelectric” if no net movement occurs. a. Alanine at pH  2.0 b. Valine at pH  12.0 c. Aspartic acid at pH  13.0 d. Arginine at pH  1.0

20.37 A direct current was passed through a solution containing va-

line, histidine, and aspartic acid at a pH of 6.0. One amino acid migrated to the positive electrode, one migrated to the negative electrode, and one did not migrate to either electrode. Which amino acids went where? 20.38 A direct current was passed through a solution containing alanine, arginine, and glutamic acid at a pH of 6.0. One amino acid migrated to the positive electrode, one migrated to the negative electrode, and one did not migrate to either electrode. Which amino acids went where? Cysteine and Disulfide Bonds (Section 20.5) 20.39 When two cysteine molecules dimerize, what happens to the R groups present? 20.40 What chemical reaction involving the cysteine molecule produces a disulfide bond? Peptides (Section 20.6) 20.41 What two functional groups are involved in the formation of a

peptide bond?

20.42 What is meant by the N-terminal end and the C-terminal end of

a peptide?

20.43 Write out the full structure of the tripeptide Val–Phe–Cys. 20.44 Write out the full structure of the tripeptide Glu–Ala–Leu. 20.45 Explain why the notations Ser–Cys and Cys–Ser represent two

different molecules rather than the same molecule. 20.46 Explain why the notations Ala–Gly–Val–Ala and Ala–Val– Gly–Ala represent two different molecules rather than the same molecule.

20.47 There are a total of six different amino acid sequences for a

tripeptide containing one molecule each of serine, valine, and glycine. Using three-letter abbreviations for the amino acids, draw the six possible sequences of amino acids. 20.48 There are a total of six different amino acid sequences for a tetrapeptide containing two molecules each of serine and valine. Using three-letter abbreviations for the amino acids, draw the six possible sequences of amino acids. 20.49 Identify the amino acids contained in each of the following

tripeptides. a.

O H O H B A B A H3NOCHOC ONOCHO C ONOCHO COO⫺ A A A CH3 CH2 CH2 A A SH OH b. O H O H B A B A ⫹ H3NOCHOCONOCHO C ONOCHO COO⫺ A A A CH2 CHOOH CH2 A A A COO⫺ CH3 C ONH2 B O ⫹

20.50 Identify the amino acids contained in each of the following

tripeptides. a.

O H O H B A B A H3NO CH2OCONOCHO CONOCH2 OCOO⫺ A CHO CH3 A CH3 b. O H O H B A B A ⫹ H3NOCHOC ONOCHO C ONOCHO COO⫺ A A A CH2 CH2 CH2 A A A CHO CH3 CH2 OH A A CH3 COO⫺ ⫹

20.51 How many peptide bonds are present in each of the molecules

in Problem 20.49?

20.52 How many peptide bonds are present in each of the molecules

in Problem 20.50?

20.53 With the help of Table 20.1, assign an IUPAC name to each of

the following small peptides. a. Ser–Cys b. Gly–Ala–Val c. Tyr–Asp–Gln d. Leu–Lys–Trp–Met 20.54 With the help of Table 20.1, assign an IUPAC name to each of the following small peptides. a. Cys–Ser b. Val–Ala–Gly c. Tyr–Gln–Asp d. Phe–Met–Tyr–Asn 20.55 What are the two repeating units present in the “backbone” of a

peptide?

20.56 For a peptide, describe

a. the regularly repeating part of its structure. b. the variable part of its structure.

Biochemically Important Small Peptides (Section 20.7) 20.57 Contrast the structures of the protein hormones oxytocin and

vasopressin in terms of a. what they have in common. b. how they differ. 20.58 Contrast the protein hormones oxytocin and vasopressin in terms of their biochemical functions.

20.59 Contrast the binding-site locations in the brain for enkephalins

and the prescription painkillers morphine and codeine.

20.60 Contrast the structures of the peptide neurotransmitters

Met-enkephalin and Leu-enkephalin in terms of a. what they have in common. b. how they differ.

20.61 What is the unusual structural feature present in the molecule

glutathione?

20.62 What is the major biochemical function of glutathione?

General Structural Characteristics of Proteins (Section 20.8) 20.63 What is the major difference between a monomeric protein and a multimeric protein? 20.64 What is the major difference between a simple protein and a conjugated protein? 20.65 Indicate whether each of the following statements about

proteins is true or false.

Exercises and Problems

a. Two or more peptide chains are always present in a multimeric protein. b. A simple protein contains only one type of amino acid. c. A conjugated protein can also be a monomeric protein. d. The prosthetic group(s) present in a glycoprotein are carbohydrate groups. 20.66 Indicate whether each of the following statements about proteins is true or false. a. Conjugated proteins always have only one peptide chain. b. All peptide chains in a multimeric protein must be identical to each other. c. A simple protein can also be a multimeric protein. d. Both monomeric proteins and multimeric proteins can contain prosthetic groups. Primary Protein Structure (Section 20.9) 20.67 What is meant by the primary structure of a protein? 20.68 Two proteins with the same amino acid composition do not

have to have the same primary structure. Explain why.

20.69 What type of bond is responsible for the primary structure of a

protein? 20.70 A segment of a protein contains two alanine and two glycine amino acid residues. How many different primary structures are possible for this segment of the protein? Secondary Protein Structure (Section 20.10) 20.71 What are the two common types of secondary protein structure? 20.72 Hydrogen bonding between which functional groups stabilizes protein secondary structure arrangements? 20.73 The  pleated sheet secondary structure can be formed through

either intramolecular hydrogen bonding or intermolecular hydrogen bonding. Explain why. 20.74 The  helix secondary structure always involves intramolecular hydrogen bonding and never involves intermolecular hydrogen bonding. Explain why. 20.75 Can more than one type of secondary structure be present in the

same protein molecule? Explain your answer.

20.76 What is meant by the statement that the secondary structure of a

segment of a protein is “unstructured”?

20.77 What is the function of the “unstructured” secondary structure

portions of a protein? 20.78 Why is the term “unstructured segment” of a protein somewhat of a misnomer? Tertiary Protein Structure (Section 20.11) 20.79 State the four types of attractive forces that give rise to tertiary protein structure. 20.80 What is the difference between the types of hydrogen bonding that occur in secondary and tertiary protein structure. 20.81 Give the type of amino acid R group that is involved in each of

the following interactions that contribute to tertiary protein structure. a. Hydrophobic interaction b. Hydrogen bond c. Disulfide bond d. Electrostatic interaction 20.82 Classify each of the interactions listed in Problem 20.81 as a covalent bond or as a noncovalent interaction.

20.83 With the help of Table 20.1, specify the nature of each of the

following tertiary-structure interactions, using the choices

695

hydrophobic, electrostatic, hydrogen bonding, and disulfide bond. a. Phenylalanine and leucine b. Arginine and glutamic acid c. Two cysteines d. Serine and tyrosine 20.84 With the help of Table 20.1, specify the nature of each of the following tertiary-structure interactions using the choices hydrophobic, electrostatic, hydrogen bonding, and disulfide bond. a. Lysine and aspartic acid b. Threonine and tyrosine c. Alanine and valine d. Leucine and isoleucine Quaternary Protein Structure (Section 20.12) 20.85 What is meant by the quaternary structure of a protein? 20.86 Not all proteins have quaternary structure. Explain why this is so. 20.87 Compare the types of noncovalent interactions that contribute to

tertiary protein structure with those that contribute to quaternary protein structure. 20.88 Quaternary protein structure is more easily disrupted than tertiary protein structure. Explain why this is so. Protein Classification Based on Shape (Section 20.13) 20.89 Contrast fibrous and globular proteins in terms of a. solubility characteristics in water. b. general biochemical function. 20.90 Contrast fibrous and globular proteins in terms of a. general secondary structure. b. relative abundance within the human body. 20.91 Classify each of the following proteins as a globular protein or

a fibrous protein. b. Collagen a. -Keratin c. Hemoglobin d. Myoglobin 20.92 What is the major biochemical function for each of the following proteins? b. Collagen a. -Keratin c. Hemoglobin d. Myoglobin 20.93 Contrast the structures of the proteins  keratin and collagen. 20.94 Contrast the structures of the proteins myoglobin and

hemoglobin.

Protein Classification Based on Function (Section 20.14) 20.95 Using the list in Section 20.14, characterize each of the following proteins in terms of its function classification. a. Actin b. Myoglobin c. Transferrin d. Insulin 20.96 Using the list in Section 20.14, characterize each of the following proteins in terms of its function classification. a. Collagen b. Hemoglobin c. Ferritin d. Casein Protein Hydrolysis (Section 20.15) 20.97 Will hydrolysis of the dipeptides Ala–Val and Val–Ala yield the

same products? Explain your answer.

20.98 A shampoo bottle lists “partially hydrolyzed protein” as one of

its ingredients. What is the difference between partially hydrolyzed protein and completely hydrolyzed protein?

20.99 Drugs that are proteins, such as insulin, must always be injected

rather than taken by mouth. Explain why.

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Chapter 20 Proteins

20.100 Which structural levels of a protein are affected by hydrolysis? 20.101 Identify the primary structure of a hexapeptide containing six

different amino acids if the following smaller peptides are among the partial-hydrolysis products: Ala–Gly, His–Val–Arg, Ala–Gly–Met, and Gly–Met–His. 20.102 Identify the primary structure of a hexapeptide containing five different amino acids if the following smaller peptides are among the partial-hydrolysis products: Gly–Cys, Ala–Ser, Ala–Gly, and Cys–Val–Ala.

20.111 What is the function of the carbohydrate groups present in

collagen?

20.112 What is the role of vitamin C in the biosynthesis of collagen? 20.113 What is the difference between an antigen and an antibody? 20.114 What is an immunoglobulin? 20.115 Describe the structural features of a typical immunoglobulin

molecule.

20.116 Describe the process by which blood immunoglobulins help

protect the body from invading bacteria and viruses.

20.103 How many different di- and tripeptides could be present in a

solution of partially hydrolyzed Ala–Gly–Ser–Tyr?

20.104 How many different di- and tripeptides could be present in a

solution of partially hydrolyzed Ala–Gly–Ala–Gly?

Protein Denaturation (Section 20.16) 20.105 Which structural levels of a protein are affected by denaturation? 20.106 Suppose a sample of protein is completely hydrolyzed and another sample of the same protein is denatured. Compare the final products of these processes. 20.107 In what way is the protein in a cooked egg the same as that in

a raw egg? 20.108 Why is 70% ethanol rather than pure ethanol preferred for use as an antiseptic agent? Glycoproteins (Section 20.17) 20.109 What two nonstandard amino acids are present in collagen? 20.110 Where are the carbohydrate units located in collagen?

Lipoproteins (Section 20.18) 20.117 Describe the general overall structure of a plasma lipoprotein. 20.118 In what chemical form does cholesterol usually exist in the

bloodstream?

20.119 What are the four major classes of plasma lipoproteins? 20.120 What do the designations VLDL, LDL, and HDL stand for? 20.121 What factor determines the density of a plasma lipoprotein? 20.122 As the lipid content of a plasma lipoprotein increases does its

density increase or decrease?

20.123 What is the biochemical function for the following?

a. Chylomicrons b. Low-density lipoproteins 20.124 What is the biochemical function for the following? a. Very-low-density lipoproteins b. High-density lipoproteins

A DD D IT IO NAL P R O BL L EM S 20.125 State whether each of the following statements applies to

primary, secondary, tertiary, or quaternary protein structure. a. A disulfide bond forms between two cysteine residues in the same protein chain. b. A salt bridge forms between amino acids with acidic and basic side chains. c. Hydrogen bonding between carbonyl oxygen atoms and nitrogen atoms of amino groups causes a peptide to coil into a helix. d. Peptide linkages hold amino acids together in a polypeptide chain. 20.126 What is the common name for each of the following IUPACnamed standard amino acids? a. 2-Aminopropanoic acid b. 2-Amino-4-methylpentanoic acid c. 2-Amino-3-hydroxybutanoic acid d. 2-Aminobutanedioic acid 20.127 What is the net charge at a pH of 1.0 for each of the following peptides? a. Val–Ala–Leu b. Tyr–Trp–Thr c. Asp–Asp–Glu–Gly d. His–Arg–Ser–Ser

20.128 What is the net charge at a pH of 13.0 for each of the peptides 20.129

20.130

20.131

20.132

in Problem 20.127? The amino acid isoleucine possesses two chiral centers. Draw Fischer projection formulas for the four stereoisomers that are possible for this amino acid. Indicate how many structurally isomeric tetrapeptides are possible for a tetrapeptide in which a. four different amino acids are present. b. three different amino acids are present. c. two different amino acids are present. Draw the structures of the three hydrolysis products obtained when the tripeptide in part a of Problem 20.49 undergoes hydrolysis under a. low-pH (acidic) conditions. b. high-pH (basic) conditions. Classify each of the following proteins as a simple protein, a conjugated protein, a glycoprotein, a lipoprotein, a fibrous protein, or a globular protein. More than one classification may apply to a given protein. b. Hemoglobin a. ␣ Keratin c. Myoglobin d. Collagen

Multiple-Choice Practice Test

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multiple-Choice Practice Test 20.133 Which of the following sets of four elements are found in all

20.134

20.135

20.136

20.137

amino acids? a. C, H, O, S b. C, H, S, N c. C, H, O, N d. C, O, S, N Which of the following statements concerning the structure of -amino acids is correct? a. The amino group is attached to the carbon atom of the carboxyl group. b. The amino group and the carboxyl group are directly bonded to the same carbon atom. c. The amino acid contains only two carbon atoms. d. The amino acid contains only one carbon atom. Which of the following is an incorrect statement about glycine, the amino acid with the simplest structure? a. It does not contain a chiral center. b. It has a side chain that does not contain the element carbon. c. It is one of the 20 standard amino acids. d. Its amino group and carboxyl group are directly bonded to each other. In a solution of high pH, all of the acidic and basic sites in an amino acid are which of the following? a. Protonated b. Deprotonated c. Positively charged d. Negatively charged Which of the standard amino acids exist as zwitterions in the solid state? a. All of them b. Only those that have nonpolar side chains

20.138

20.139

20.140

20.141

20.142

c. Only those that are polar neutral d. Only those that are acidic or basic Which of the following statements concerning the tripeptide Val–Ala–Gly is correct? a. The C-terminal amino acid residue is Val. b. The N-terminal amino acid residue is Gly. c. Its structure can also be written as Gly–Ala–Val. d. It is constitutionally isomeric with five other tripeptides. Which of the following types of bonding is responsible for protein secondary structure? a. Peptide linkages b. Amide linkages c. Hydrogen bonds d. Bonds involving R groups R-group interaction between which of the following pairs of amino acids produces a covalent bond? a. Cysteine–cysteine b. Proline–proline c. Alanine–glycine d. Valine–lysine Which of the following levels of protein structure is not disrupted when protein denaturation occurs? a. Primary structure b. Secondary structure c. Tertiary structure d. Quaternary structure In which of the following pairs of proteins are both members of the pair fibrous proteins? a. a-Keratin and collagen b. Collagen and hemoglobin c. Hemoglobin and myoglobin d. a-Keratin and hemoglobin

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Enzymes and Vitamins Chapter Outline 21.1 General Characteristics of Enzymes 698 21.2 Enzyme Structure 699

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21.3 Nomenclature and Classification of Enzymes 699 21.4 Models of Enzyme Action 704 21.5 Enzyme Specificity 705 21.6 Factors That Affect Enzyme Activity 706

CHEMISTRY AT A GLANCE: Enzyme Activity 709 21.7 Enzyme Inhibition 710

CHEMISTRY AT A GLANCE: Enzyme Inhibition 712 21.8 Regulation of Enzyme Activity 713 21.9 Antibiotics That Inhibit Enzyme Activity 715 21.10 Medical Uses of Enzymes 718 21.11 General Characteristics of Vitamins 718 21.12 Water-Soluble Vitamins 721 21.13 Fat-Soluble Vitamins 725

CHEMICAL CONNECTIONS H. pylori and Stomach Ulcers 707 Enzymatic Browning: Discoloration of Fruits and Vegetables 708 Heart Attacks and Enzyme Analysis 709

The microbial life present in hot springs and thermal vents possesses enzymes that are specially adapted to higher temperature conditions.

I

n this chapter we consider two topics: enzymes and vitamins. Enzymes govern all chemical reactions in living organisms. They are specialized proteins that, with fascinating precision and selectivity, catalyze biochemical reactions that store and release energy, make pigments in our hair and eyes, digest the food we eat, synthesize cellular building materials, and protect us by repairing cellular damage and clotting our blood. Enzymes are sensitive to their environment, responding quickly to changes in the cell. The deficiency or excess of particular enzymes can cause certain diseases or signal problems such as heart attacks and other organ damage. Our knowledge of protein structure (Chapter 20) can help us appreciate and better understand how enzymes function in living cells. Vitamins, which are necessary components of a healthful diet, play important roles in cellular metabolism. In most cases, they function as enzyme cofactors or carriers of functional groups during biosynthesis.

21.1 GENERAL CHARACTERISTICS OF ENZYMES An enzyme is an organic compound that acts as a catalyst for a biochemical reaction. Each cell in the human body contains thousands of different enzymes because almost every reaction in a cell requires its own specific enzyme. Enzymes cause cellular reactions to occur millions of times faster than corresponding uncatalyzed reactions. As catalysts (Section 9.6), enzymes are not consumed during the reaction but merely help the reaction occur more rapidly. The word enzyme comes from the Greek words en, which means “in,” and zyme, which means “yeast.” Long before their chemical nature was understood, yeast enzymes were used in the production of bread and alcoholic beverages. The action of yeast on sugars

698 Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

21.3 Nomenclature and Classification of Enzymes

Figure 21.1 Bread dough rises as the result of carbon dioxide production resulting from the action of yeast enzymes on sugars present in the dough.

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produces the carbon dioxide gas that causes bread to rise (see Figure 21.1). Fermentation of sugars in fruit juices with the same yeast enzymes produces alcoholic beverages. Most enzymes are globular proteins (Section 20.13). Some are simple proteins, consisting entirely of amino acid chains. Others are conjugated proteins, containing additional chemical components (Section 21.2). Until the 1980s, it was thought that all enzymes were proteins. A few enzymes are now known that are made of ribonucleic acids (RNA; Section 22.7) and that catalyze cellular reactions involving nucleic acids. In this chapter, we will consider only enzymes that are proteins. Enzymes undergo all the reactions of proteins, including denaturation (Section 20.16). Slight alterations in pH, temperature, or other protein denaturants affect enzyme activity dramatically. Good cooks realize that overheating yeast kills the action of the yeast. A person suffering from a high fever (greater than 106⬚F) runs the risk of denaturing certain enzymes. The biochemist must exercise extreme caution in handling enzymes to avoid the loss of their activity. Even vigorous shaking of an enzyme solution can destroy enzyme activity. Enzymes differ from nonbiochemical (laboratory) catalysts not only in size, being much larger, but also in that their activity is usually regulated by other substances present in the cell in which they are found. Most laboratory catalysts need to be removed from a reaction mixture to stop their catalytic action; this is not so with enzymes. In some cases, if a certain chemical is needed in the cell, the enzyme responsible for its production is activated by other cellular components. When a sufficient quantity has been produced, the enzyme is then deactivated. In other situations, the cell may produce more or less enzyme as required. Because different enzymes are required for nearly all cellular reactions, certain necessary reactions can be accelerated or decelerated without affecting the rest of the cellular chemistry.

21.2 ENZYME STRUCTURE Enzymes, the most efficient catalysts known, increase the rates of biochemical reactions by factors of up to 1020 over uncatalyzed reactions. Nonenzymatic catalysts, on the other hand, typically enhance the rate of a reaction by factors of 102 to 104.

Enzymes can be divided into two general structural classes: simple enzymes and conjugated enzymes. A simple enzyme is an enzyme composed only of protein (amino acid chains). A conjugated enzyme is an enzyme that has a nonprotein part in addition to a protein part. By itself, neither the protein part nor the nonprotein portion of a conjugated enzyme has catalytic properties. An apoenzyme is the protein part of a conjugated enzyme. A cofactor is the nonprotein part of a conjugated enzyme. It is the combination of apoenzyme with cofactor that produces a biochemically active enzyme. A holoenzyme is the biochemically active conjugated enzyme produced from an apoenzyme and a cofactor. Apoenzyme ⫹ cofactor ⫽ holoenzyme Why do apoenzymes need cofactors? Cofactors provide additional chemically reactive functional groups besides those present in the amino acid side chains of apoenzymes. A cofactor is generally either a small organic molecule or an inorganic ion (usually a metal ion). A coenzyme is a small organic molecule that serves as a cofactor in a conjugated enzyme. Many vitamins (Section 21.11) have coenzyme functions in the human body. Typical inorganic ion cofactors include Zn2⫹, Mg2⫹, Mn2⫹, and Fe2⫹. The nonmetallic Cl⫺ ion occasionally acts as a cofactor. Dietary minerals are an important source of inorganic ion cofactors.

21.3 NOMENCLATURE AND CLASSIFICATION OF ENZYMES Enzymes are most commonly named by using a system that attempts to provide information about the function (rather than the structure) of the enzyme. Type of reaction catalyzed and substrate identity are focal points for the nomenclature. A substrate is the reactant in an enzyme-catalyzed reaction. The substrate is the substance upon which the enzyme “acts.”

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Chapter 21 Enzymes and Vitamins

Three important aspects of the enzyme-naming process are the following: 1. The suffix -ase identifies a substance as an enzyme. Thus urease, sucrase, and lipase are all enzyme designations. The suffix -in is still found in the names of some of the first enzymes studied, many of which are digestive enzymes. Such names include trypsin, chymotrypsin, and pepsin. 2. The type of reaction catalyzed by an enzyme is often noted with a prefix. An oxidase enzyme catalyzes an oxidation reaction, and a hydrolase enzyme catalyzes a hydrolysis reaction. 3. The identity of the substrate is often noted in addition to the type of reaction. Enzyme names of this type include glucose oxidase, pyruvate carboxylase, and succinate dehydrogenase. Infrequently, the substrate but not the reaction type is given, as in the names urease and lactase. In such names, the reaction involved is hydrolysis; urease catalyzes the hydrolysis of urea, lactase the hydrolysis of lactose.

EXAMPLE 21.1 Predicting Enzyme Function from an Enzyme’s Name

Predict the function of the following enzymes. a. Cellulase c. L-Amino acid oxidase

b. Sucrase d. Aspartate aminotransferase

Solution

a. b. c. d.

Cellulase catalyzes the hydrolysis of cellulose. Sucrase catalyzes the hydrolysis of the disaccharide sucrose. L-Amino acid oxidase catalyzes the oxidation of L-amino acids. Aspartate aminotransferase catalyzes the transfer of an amino group from aspartate to a different molecule.

Practice Exercise 21.1 Predict the function of the following enzymes. a. b. c. d.

Maltase Lactate dehydrogenase Fructose oxidase Maleate isomerase

Answers: a. Hydrolysis of maltose; b. Removal of hydrogen from lactate ion; c. Oxidation of fructose; d. Rearrangement (isomerization) of maleate ion

B

F

Recall from Section 14.9 that for organic redox reactions, the following two operational rules are used instead of oxidation numbers (Section 9.2) to characterize oxidation and reduction processes: 1. An organic oxidation reaction is an oxidation that increases the number of C—O bonds and/or decreases the number of C—H bonds. 2. An organic reduction reaction is a reduction that decreases the number of C—O bonds and/or increases the number of C—H bonds.

Enzymes are grouped into six major classes on the basis of the types of reactions they catalyze. 1. An oxidoreductase is an enzyme that catalyzes an oxidation–reduction reaction. Because oxidation and reduction are not independent processes but linked processes that must occur together (Section 9.3), an oxidoreductase requires a coenzyme that is oxidized or reduced as the substrate is reduced or oxidized. Lactate dehydrogenase is an oxidoreductase that removes hydrogen atoms from a molecule. COO⫺ A HO OC OH ⫹ NAD⫹ A CH3

COO⫺ A ⫹ CP O ⫹ NADH ⫹ H A CH3 Pyruvate

Lactate Reduced substrate

Lactate dehydrogenase

Oxidized coenzyme

Oxidized product

Reduced coenzyme

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21.3 Nomenclature and Classification of Enzymes

2. A transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another. Two major subtypes of transferases are transaminases and kinases. A transaminase catalyzes the transfer of an amino group from one molecule to another. Kinases, which play a major role in metabolic energy-production reactions (see Section 24.2), catalyze the transfer of a phosphate group from adenosine triphosphate (ATP) to give adenosine diphosphate (ADP) and a phosphorylated product (a product containing an additional phosphate group). H

H HO O O C OH

P O O O C OH O

HO

O

⫹ ATP

OH

Hexokinase

88888888n ADP

⫹

OH

Glucose

OH

HO

OH

OH OH

Adenosine triphosphate

Adenosine diphosphate

Glucose 6-phosphate

(3 phosphate groups present)

(2 phosphate groups present)

The symbol P is a shorthand notation for a PO32– unit.

3. A hydrolase is an enzyme that catalyzes a hydrolysis reaction in which the addition of a water molecule to a bond causes the bond to break. Hydrolysis reactions are central to the process of digestion. Carbohydrases effect the breaking of glycosidic bonds in oligo- and polysaccharides, proteases effect the breaking of peptide linkages in proteins, and lipases effect the breaking of ester linkages in triacylglycerols. CH2OH O

HO

OH

CH2OH O O

OH

Maltose

Maltase ⫹ H2O 88888n

OH

CH2OH O

CH2OH O OH

HO

OH

⫹

OH

OH

HO

OH

OH OH

OH

Glucose

Glucose

4. A lyase is an enzyme that catalyzes the addition of a group to a double bond or the removal of a group to form a double bond in a manner that does not involve hydrolysis or oxidation. A dehydratase effects the removal of the components of water from a double bond and a hydratase effects the addition of the components of water to a double bond. COO⫺ A C O H ⫹ H2O B HO C A COO⫺

Fumarase

COO⫺ A HO O C O H A HO C OH A COO⫺ L-Malate

Fumarate

5. An isomerase is an enzyme that catalyzes the isomerization (rearrangement of atoms) of a substrate in a reaction, converting it into a molecule isomeric with itself. There is only one reactant and one product in reactions where isomerases are operative. COO⫺ A H O C O OH A CH2O O P 3-Phosphoglycerate

Phosphoglyceromutase

COO⫺ A H O C OOO P A CH2OH 2-Phosphoglycerate

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Chapter 21 Enzymes and Vitamins

TABLE 21.1 Main Classes and Subclasses of Enzymes

Main Classes

Selected Subclasses

Type of Reaction Catalyzed

oxidoreductases

oxidases reductases dehydrogenases

oxidation of a substrate reduction of a substrate introduction of double bond (oxidation) by formal removal of two H atoms from substrate, the H being accepted by a coenzyme

transferases

transaminases

transfer of an amino group between substrates transfer of a phosphate group between substrates

kinases

phosphatases

hydrolysis of ester linkages in lipids hydrolysis of amide linkages in proteins hydrolysis of sugar–phosphate ester bonds in nucleic acids hydrolysis of glycosidic bonds in carbohydrates hydrolysis of phosphate–ester bonds

lyases

dehydratases decarboxylases deaminases hydratases

removal of H2O from substrate removal of CO2 from substrate removal of NH3 from substrate addition of H2O to a substrate

isomerases

racemases

conversion of D to L isomer, or vice versa transfer of a functional group from one position to another in the same molecule

hydrolases

lipases proteases nucleases carbohydrases

mutases

synthetases

ligases

formation of new bond between two substrates, with participation of ATP formation of new bond between a substrate and CO2, with participation of ATP

carboxylases

6. A ligase is an enzyme that catalyzes the bonding together of two molecules into one with the participation of ATP. ATP involvement is required because such reactions are generally energetically unfavorable and they require the simultaneous input of energy obtained by a hydrolysis reaction in which ATP is converted to ADP (such energy release is considered in Section 23.3).

Pyruvate

Pyruvate carboxylase

COO⫺ A C O ⫹ ADP ⫹ P ⫹ H⫹ A Phosphate CH2 A COO⫺

B

B

CO2

COO⫺ A ⫹ C O ⫹ ATP A CH3

Oxaloacetate

Within each of these six main classes of enzymes there are enzyme subclasses. Table 21.1 gives further information about enzyme subclass terminology, some of which was used in the preceding discussion of the main enzyme classes. For example, dehydratases and hydratases are subclass designations; both of these enzyme subtypes are lyases (see Table 21.1).

21.3 Nomenclature and Classification of Enzymes

Classifying Enzymes by the Type of Chemical Reaction They Catalyze

To what main enzyme class do the enzymes that catalyze the following chemical reactions belong?

b.

COO⫺ A C O ⫹ NADH ⫹ H⫹ A CH2 A COO⫺

B

COO⫺ A ⫹ HO O C OH ⫹ NAD A CH2 A COO⫺

a.

H O A B ⫺ O CHOCOO⫺ H3NO CHOCOO ⫹ H2N ⫹ A A R1 R2

O H B A H3NO CHOCONOCHOCOO⫺ ⫹ H2O A A R1 R2 ⫹

⫹

Solution

a. In this reaction two H atoms are removed from the substrate and a carbon–oxygen double bond is formed. Loss of two hydrogen atoms by a molecule is an indication of oxidation. This is an oxidation–reduction reaction and the enzyme needed to effect the change will be an oxidoreductase.

B

A

HO

COO⫺ A C O ⫹ NADH ⫹ H⫹ A CH2 A COO⫺

A

COO⫺ A C H ⫹ NAD⫹ A CH2 A COO⫺

Malate

Oxaloacetate

b. In this reaction the components of a molecule of H2O are added to the substrate ( a dipeptide) with the resulting breaking of the peptide bond to produce two amino acids. This is an example of a hydrolysis reaction. An enzyme that effects such a change is called a hydrolase. H O A B ⫺ O CHOCOO⫺ H3NO CHOCOO ⫹ H2N ⫹ A A R1 R2

O H B A H3NO CHOCONOCHOCOO⫺ ⫹ H2O A A R1 R2 ⫹

⫹

Dipeptide

Amino acid

Amino acid

Practice Exercise 21.2 To what main enzyme class do the enzymes that catalyze the following chemical reactions belong? a.

O

P OOOCH2 A A HO

HO A

CH2OH A ⫹ ATP A OH

ADP ⫹

Fructose 6-phosphate

b.

A

A

P

P

C

Answers: a. Transferase; b. Lyase

A

2-Phosphoglycerate

O HO A

CH2OO P A A OH

Fructose 1,6-bisphosphate

COO⫺ A C O P ⫹ HOH

A

A

HO

A

A

H

COO⫺ A C O A C H A H

P OOOCH2 A A HO

H

A

EXAMPLE 21.2

703

H

Phosphoenolpyruvate

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Chapter 21 Enzymes and Vitamins

Active site Substrate

21.4 MODELS OF ENZYME ACTION Explanations of how enzymes function as catalysts in biochemical systems are based on the concepts of an enzyme active site and enzyme–substrate complex formation.

Enzyme Active Site

Figure 21.2 The active site of an enzyme is usually a crevicelike region formed as a result of the protein’s secondary and tertiary structural characteristics.

Studies show that only a small portion of an enzyme molecule called the active site participates in the interaction with a substrate or substrates during a reaction. The active site is the relatively small part of an enzyme’s structure that is actually involved in catalysis. The active site in an enzyme is a three-dimensional entity formed by groups that come from different parts of the protein chain(s); these groups are brought together by the folding and bending (secondary and tertiary structure; Sections 20.10 and 20.11) of the protein. The active site is usually a “crevicelike” location in the enzyme (see Figure 21.2).

Enzyme–Substrate Complex Catalysts offer an alternative pathway with lower activation energy through which a reaction can occur (Section 9.6). In enzyme-controlled reactions, this alternative pathway involves the formation of an enzyme–substrate complex as an intermediate species in the reaction. An enzyme–substrate complex is the intermediate reaction species that is formed when a substrate binds to the active site of an enzyme. Within the enzyme–substrate complex, the substrate encounters more favorable reaction conditions than if it were free. The result is faster formation of product.

Lock-and-Key Model The lock-and-key model is more than just a “shape fit.” In addition, there are weak binding forces (R group interactions) between parts.

To account for the highly specific way an enzyme recognizes a substrate and binds it to the active site, researchers have proposed several models. The simplest of these models is the lock-and-key model. In the lock-and-key model, the active site in the enzyme has a fixed, rigid geometrical conformation. Only substrates with a complementary geometry can be accommodated at such a site, much as a lock accepts only certain keys. Figure 21.3 illustrates the lock-and-key concept of substrate–enzyme interaction.

Induced-Fit Model The lock-and-key model explains the action of numerous enzymes. It is, however, too restrictive for the action of many other enzymes. Experimental evidence indicates that many enzymes have flexibility in their shapes. They are not rigid and static; there is constant change in their shape. The induced-fit model is used for this type of situation. The induced-fit model allows for small changes in the shape or geometry of the active site of an enzyme to accommodate a substrate. A good analogy is the changes that occur in the shape of a glove when a hand is inserted into it. The induced fit is a result of the enzyme’s flexibility; it adapts to accept the incoming substrate. This model, illustrated in Figure 21.4, is a more thorough explanation for the active-site properties of an enzyme because it includes the specificity of the lock-and-key model coupled with the flexibility of the enzyme protein. Figure 21.3 The lock-and-key model for enzyme activity. Only a substrate whose shape and chemical nature are complementary to those of the active site can interact with the enzyme.

Products Substrate

Enzyme active site

Enzyme active site

21.5 Enzyme Specificity

Figure 21.4 The induced-fit model for enzyme activity. The enzyme active site, although not exactly complementary in shape to that of the substrate, is flexible enough that it can adapt to the shape of the substrate.

705

Products Substrate

Enzyme active site

Enzyme active site

The forces that draw the substrate into the active site are many of the same forces that maintain tertiary structure in the folding of peptide chains. Electrostatic interactions, hydrogen bonds, and hydrophobic interactions all help attract and bind substrate molecules. For example, a protonated (positively charged) amino group in a substrate could be attracted and held at the active site by a negatively charged aspartate or glutamate residue. Alternatively, cofactors such as positively charged metal ions often help bind substrate molecules. Figure 21.5 is a schematic representation of the amino acid R group interactions that bind a substrate to an enzyme active site.

21.5 ENZYME SPECIFICITY Enzymes exhibit different levels of selectivity, or specificity, for substrates. The degree of enzyme specificity is determined by the active site. Some active sites accommodate only one particular compound, whereas others can accommodate a “family” of closely related compounds. Types of enzyme specificity include 1. Absolute Specificity. Such specificity means an enzyme will catalyze a particular reaction for only one substrate. This most restrictive of all specificities is not common. Urease is an enzyme with absolute specificity. 2. Stereochemical Specificity. Such specificity means an enzyme can distinguish between stereoisomers. Chirality is inherent in an active site, because amino acids are chiral compounds. L-Amino-acid oxidase will catalyze reactions of L-amino acids but not of D-amino acids. 3. Group Specificity. Such specificity involves structurally similar compounds that have the same functional groups. Carboxypeptidase is group-specific; it cleaves amino acids, one at a time, from the carboxyl end of the peptide chain. 4. Linkage Specificity. Such specificity involves a particular type of bond, irrespective of the structural features in the vicinity of the bond. Phosphatases hydrolyze phosphate– ester bonds in all types of phosphate esters. Linkage specificity is the most general of the specificities considered.

Figure 21.5 A schematic diagram representing amino acid R group interactions that bind a substrate to an enzyme active site. The R group interactions that maintain the threedimensional structure of the enzyme (secondary and tertiary structure) are also shown.

Substrate R group interactions that bind the substrate to the enzyme active site R group interactions that maintain the three-dimensional structure of the enzyme Noninteracting R groups that help determine the solubility of the enzyme

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Chapter 21 Enzymes and Vitamins

Increased number of enzyme– Optimum substrate temperature collisions

21.6 FACTORS THAT AFFECT ENZYME ACTIVITY Enzyme activity is a measure of the rate at which an enzyme converts substrate to products in a biochemical reaction. Four factors affect enzyme activity: temperature, pH, substrate concentration, and enzyme concentration.

Reaction rate

Temperature

Denaturation due to excess heat

Temperature

Figure 21.6 A graph showing the effect of temperature on the rate of an enzymatic reaction.

The upper temperature limit for life now stands at 121⬚C as the result of the discovery, in 2004, of a new “heat-loving” microbe. The microbe was found in a water sample from a hydrothermal vent deep in the Northeast Pacific Ocean. Its method of respiration involves reduction of Fe(III) to Fe(II) to produce energy.

Reaction rate

Maximum rate

Temperature is a measure of the kinetic energy (energy of motion) of molecules. Higher temperatures mean molecules are moving faster and colliding more frequently. This concept applies to collisions between substrate molecules and enzymes. As the temperature of an enzymatically catalyzed reaction increases, so does the rate (velocity) of the reaction. However, when the temperature increases beyond a certain point, the increased energy begins to cause disruptions in the tertiary structure of the enzyme; denaturation is occurring. Change in tertiary structure at the active site impedes catalytic action, and the enzyme activity quickly decreases as the temperature climbs past this point (Figure 21.6). The temperature that produces maximum activity for an enzyme is known as the optimum temperature for that enzyme. Optimum temperature is the temperature at which an enzyme exhibits maximum activity. For human enzymes, the optimum temperature is around 37⬚C, normal body temperature. A person who has a fever where body core temperature exceeds 40⬚C can be in a life-threatening situation because such a temperature is sufficient to initiate enzyme denaturation. The loss of function of critical enzymes, particularly those of the central nervous system, can result in dysfunction sufficient to cause death. The “destroying” effect of temperature on bacterial enzymes is used in a hospital setting to sterilize medical instruments and laundry. In high-temperature high-pressure vessels called autoclaves super-heated steam is used to produce a temperature sufficient to denature bacterial enzymes. Not all enzymes have optimal temperatures around the physiological temperature of 37⬚C. This is particularly true for enzymes found in microbes associated with hydrothermal areas such as those in Yellowstone National Park and hydrothermal vents on the ocean floor, where temperature and pressure can be extremely high. The ability of microbial enzymes to survive under such harsh conditions is related to the amino acid sequences in their protein structures, sequences that are stable under such extraordinary conditions. Microbial enzymes that survive in such extreme environments are collectively called extremozymes. The study of extremozymes is an area of special interest for industrial chemists. Enzymes can function as catalysts for industrial processes, just as they do for biochemical reactions, provided they can survive the conditions associated with the process. Because industrial processes usually require higher temperature and pressure than physiological processes, extremozymes can be useful. The enzymes present in some detergent formulations, which must function in hot water, are the result of research associated with high-temperature microbial enzymes.

pH

Optimum pH

5

7

9

pH

Figure 21.7 A graph showing the effect of pH on the rate of an enzymatic reaction.

The pH of an enzyme’s environment can affect its activity. This is not surprising because the charge on acidic and basic amino acids (Section 20.2) located at the active site depends on pH. Small changes in pH (less than one unit) can result in enzyme denaturation (Section 20.16) and subsequent loss of catalytic activity. Most enzymes exhibit maximum activity over a very narrow pH range. Only within this narrow pH range do the enzyme’s amino acids exist in properly charged forms (Section 20.4). Optimum pH is the pH at which an enzyme exhibits maximum activity. Figure 21.7 shows the effect of pH on an enzyme’s activity. Biochemical buffers help maintain the optimum pH for an enzyme. Each enzyme has a characteristic optimum pH, which usually falls within the physiological pH range of 7.0–7.5. Notable exceptions to this generalization are the digestive

21.6 Factors That Affect Enzyme Activity

Reaction rate (velocity)

Maximum reaction rate

Rate approaches maximum

707

enzymes pepsin and trypsin. Pepsin, which is active in the stomach, functions best at a pH of 2.0. On the other hand, trypsin, which operates in the small intestine, functions best at a pH of 8.0. The amino acid sequences present in pepsin and trypsin are those needed such that the R groups present can maintain protein tertiary structure (Section 20.11) at low (2.0) and high (8.0) pH values, respectively. A variation from normal pH can also affect substrates, causing either protonation or deprotonation of groups on the substrate. The interaction between the altered substrate and the enzyme active site may be less efficient than normal—or even impossible.

Substrate Concentration Substrate concentration

Figure 21.8 A graph showing the change in enzyme activity with a change in substrate concentration at constant temperature, pH, and enzyme concentration. Enzyme activity remains constant after a certain substrate concentration is reached.

c

When the concentration of an enzyme is kept constant and the concentration of substrate is increased, the enzyme activity pattern shown in Figure 21.8 is obtained. This activity pattern is called a saturation curve. Enzyme activity increases up to a certain substrate concentration and thereafter remains constant. What limits enzymatic activity to a certain maximum value? As substrate concentration increases, the point is eventually reached where enzyme capabilities are used to their maximum extent. The rate remains constant from this point on (Figure 21.8). Each substrate must occupy an enzyme active site for a finite amount of time, and the products must leave the site before the cycle can be repeated. When each enzyme molecule is

HEMICAL

onnections

H. pylori and Stomach Ulcers

Helicobacter pylori, commonly called H. pylori, is a bacterium that can function in the highly acidic environment of the stomach. The discovery in 1982 of the existence of this bacterium in the stomach was startling to the medical profession because conventional thought at the time was that bacteria could not survive at the stomach’s pH of about 1.4. It is now known that H. pylori causes more than 90% of duodenal ulcers and up to 80% of gastric ulcers. Before this discovery, it was thought that most ulcers were caused by excess stomach acid eating the stomach lining. Contributory causes were thought to be spicy food and stress. Conventional treatment involved acid-suppression or acid-neutralization medications. Now, treatment regimens involve antibiotics. The medical profession was slow to accept the concept of a bacterial cause for most ulcers, and it was not until the mid-1990s that antibiotic treatment became common. How the enzymes present in the H. pylori bacterium can function in the acidic environment of the stomach (where they should be denatured) is now known. Present on the surface of the bacterium is the enzyme urease, an enzyme that converts urea to the basic substance ammonia. The ammonia then neutralizes acid present in its immediate vicinity; a protective barrier is thus created. The urease itself is protected from denaturation by its complex quaternary structure. H. pylori causes ulcers by weakening the protective mucous coating of the stomach and duodenum, which allows acid to get through to the sensitive lining beneath. Both the acid and the bacteria irritate the lining and cause a sore—the ulcer. Ultimately the H. pylori themselves burrow into the lining to an acid-safe area within the lining.

Approximately two-thirds of the world’s population is infected with H. pylori. In the United States 30% of the adult population is infected, with the infection most prevalent among older adults. About 20% of people under the age of 40 and half of those over 60 have it. Only one out of every six people infected with H. pylori ever suffer symptoms related to ulcers. Why H. pylori does not cause ulcers in every infected person is not known. H. pylori bacteria are most likely spread from person to person through fecal–oral or oral–oral routes. Possible environmental sources include contaminated water sources. The infection is more common in crowded living conditions with poor sanitation. In countries with poor sanitation, 90% of the adult population can be infected.

H. pylori bacteria.

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TABLE 21.2 Turnover Numbers for Selected Enzymes

Turnover Number (per minute)

Enzyme

carbonic anhydrase catalase cholinesterase penicillinase lactate dehydrogenase DNA polymerase I

Reaction Catalyzed

CO2 ⫹ H2O Δ H2CO3 2H2O2 Δ 2H2O ⫹ O2 hydrolysis of acetylcholine hydrolysis of penicillin conversion of pyruvate to lactate addition of nucleotides to DNA chains

36,000,000 5,600,000 1,500,000 120,000 60,000 900

working at full capacity, the incoming substrate molecules must “wait their turn” for an empty active site. At this point, the enzyme is said to be under saturation conditions. The rate at which an enzyme accepts substrate molecules and releases product molecules at substrate saturation is given by its turnover number. An enzyme’s turnover number is the number of substrate molecules transformed per minute by one molecule of enzyme under optimum conditions of temperature, pH, and saturation. Table 21.2 gives turnover numbers for selected enzymes. Some enzymes have a much faster mode of operation than others.

c

HEMICAL

onnections

Enzymatic Browning: Discoloration of Fruits and Vegetables

Everyone is familiar with the way fruits such as apples, pears, peaches, apricots, and bananas, and vegetables such as potatoes quickly turn brown when their tissue is exposed to oxygen. Such oxygen exposure occurs when the food is sliced or bitten into or when it has sustained bruises, cuts, or other injury to the peel. This “browning reaction” is related to the work of an enzyme called phenolase (or polyphenoloxidase), a conjugated enzyme in which copper is present. Phenolase is classified as an oxidoreductase. The substrates for phenolase are phenolic compounds present in the tissues of the fruits and vegetables. Phenolase hydroxylates monophenols to o-diphenols and oxidizes o-diphenols to o-quinones (see chemical equations below). The o-quinones then enter into a number of other reactions, which produce the “undesirable” brown discolorations. Quinone formation is enzyme- and oxygen-dependent. Once the quinones have formed, the subsequent reactions occur spontaneously and no longer depend on the presence of phenolase or oxygen. Enzymatic browning can be prevented or slowed in several ways. Immersing the “injured” food (for example, apple slices) in cold water slows the browning process. The lower temperature decreases enzyme activity, and the water limits the enzyme’s access to oxygen. Refrigeration slows enzyme activity even more, and boiling temperatures destroy (denature) the OH

At left, a freshly cut apple. Brownish oxidation products form in a few minutes (at right).

enzyme. A long-used method for preventing browning involves lemon juice. Phenolase works very slowly in the acidic environment created by the lemon juice’s presence. In addition, the vitamin C (ascorbic acid) present in lemon juice functions as an antioxidant. It is more easily oxidized than the phenolic-derived compounds, and its oxidation products are colorless.

OH

O OH

O

O2

O2

Phenolase

Phenolase

Monophenol derivatives

o-Diphenol derivatives

o-Quinone derivatives

Brownish oxidation products

21.6 Factors That Affect Enzyme Activity

709

Enzyme Activity THE MECHANISM OF ENZYME ACTION Formation of an enzyme–substrate complex as an intermediate species provides an alternative pathway, with lower activation energy, through which a reaction can occur.

Lock-and-Key Model

Induced-Fit Model

The active site has a fixed geometric shape. Only a substrate with a matching shape can fit into it.

The active site has a flexible shape that can change to accept a variety of related substrates. Enzymes vary in their degree of specificity for substrates.

Substrate

Substrates

Enzyme active site

Enzyme active site

FACTORS THAT AFFECT THE RATE OF ENZYME ACTIVITY

pH

Reaction rate increases with temperature until the point at which the protein is denatured and activity drops sharply.

Maximum enzymatic activity is possible only within a narrow pH range; outside this pH range, the protein is denatured and activity drops sharply.

Reaction rate

Temperature

Concentration of Substrate

Concentration of Enzyme

Reaction rate increases with substrate concentration until full saturation occurs; then the rate levels off.

Reaction rate increases with increasing enzyme concentration, assuming enzyme concentration is much lower than that of substrate.

Enzyme Concentration

Enzyme concentration

Figure 21.9 A graph showing the change in reaction rate with a change in enzyme concentration for an enzymatic reaction. Temperature, pH, and substrate concentration are constant. The substrate concentration is high relative to enzyme concentration.

Because enzymes are not consumed in the reactions they catalyze, the cell usually keeps the number of enzymes low compared with the number of substrate molecules. This is efficient; the cell avoids paying the energy costs of synthesizing and maintaining a large work force of enzyme molecules. Thus, in general, the concentration of substrate in a reaction is much higher than that of the enzyme. If the amount of substrate present is kept constant and the enzyme concentration is increased, the reaction rate increases because more substrate molecules can be accommodated in a given amount of time. A plot of enzyme activity versus enzyme concentration, at a constant substrate concentration that is high relative to enzyme concentration, is shown in Figure 21.9. The greater the enzyme concentration, the greater the reaction rate. The Chemistry at a Glance feature above reviews what we have said about enzyme activity.

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Chapter 21 Enzymes and Vitamins

EXAMPLE 21.3 Determining How Enzyme Activity Is Affected by Various Changes

Describe the effect that each of the following changes would have on the rate of a reaction that involves the substrate urea and the liver enzyme urease. a. b. c. d.

Increasing the urea concentration Increasing the urease concentration Increasing the temperature from its optimum value to a value 10⬚ higher than this value Lowering the pH from the optimum value of 5.0 to a value of 3.0

Solution

a. The enzyme activity rate will increase until all of the enzyme molecules are engaged with urea substrate. b. The enzyme activity rate will increase until all of the urea molecules are engaged with urease enzymes. c. At temperatures higher than the optimum temperature, enzyme activity will decrease from that at the optimum temperature. d. At pH values lower than the optimum pH value, enzyme activity will decrease from that at the optimum pH.

Practice Exercise 21.3 Describe the effect that each of the following changes would have on the rate of a reaction that involves the substrate sucrose and the intestinal enzyme sucrase. a. b. c. d.

Decreasing the sucrase concentration Increasing the sucrose concentration Lowering the temperature to 10⬚ C Raising the pH from 6.0 to 8.0 when the optimum pH is 6.2

Answers: a. Decrease rate; b. Increase rate; c. Decrease rate; d. Decrease rate

21.7 ENZYME INHIBITION B

F

The treatment for methanol poisoning involves giving a patient intravenous ethanol (Section 14.5). This action is based on the principle of competitive enzyme inhibition. The same enzyme, alcohol dehydrogenase, detoxifies both methanol and ethanol. Ethanol has 10 times the affinity for the enzyme that methanol has, keeping the enzyme busy with ethanol as the substrate gives the body time to excrete the methanol before it is oxidized to the potentially deadly formaldehyde (Section 14.5).

The rates of enzyme-catalyzed reactions can be decreased by a group of substances called inhibitors. An enzyme inhibitor is a substance that slows or stops the normal catalytic function of an enzyme by binding to it. In this section, we consider three modes by which inhibition takes place: reversible competitive inhibition, reversible noncompetitive inhibition, and irreversible inhibition.

Reversible Competitive Inhibition In Section 21.5 we noted that enzymes are quite specific about the molecules they accept at their active sites. Molecular shape and charge distribution are key determining factors in whether an enzyme accepts a molecule. A competitive enzyme inhibitor is a molecule that sufficiently resembles an enzyme substrate in shape and charge distribution that it can compete with the substrate for occupancy of the enzyme’s active site. When a competitive inhibitor binds to an enzyme active site, the inhibitor remains unchanged (no reaction occurs), but its physical presence at the site prevents a normal substrate molecule from occupying the site. The result is a decrease in enzyme activity. The formation of an enzyme–competitive inhibitor complex is a reversible process because it is maintained by weak interactions (hydrogen bonds, etc.). With time (fractions of a second), the complex breaks up. The empty active site is then available for a new occupant. Substrate and inhibitor again compete for the empty active site. Thus the active site of an enzyme binds either inhibitor or normal substrate on a random basis. If inhibitor concentration is greater than substrate concentration, the inhibitor dominates the occupancy process. The reverse is also true. Competitive inhibition can be reduced by simply increasing the concentration of the substrate.

21.7 Enzyme Inhibition

Normal substrate

Enzyme

(a)

Competitive inhibitor

Enzyme

(b)

Figure 21.10 A comparison of an enzyme with a substrate at its active site (a) and an enzyme with a competitive inhibitor at its active site (b).

711

Figure 21.10 compares the binding of a normal substrate and that of a competitive inhibitor at an enzyme’s active site. Note that the portions of these two molecules that bind to the active site have the same shape but that the two molecules differ in overall shape. It is because of this overall difference in shape that the substrate reacts at the active site but the inhibitor does not. Numerous drugs act by means of competitive inhibition. For example, antihistamines are competitive inhibitors of histidine decarboxylation, the enzymatic reaction that converts histidine to histamine. Histamine causes the usual allergy and cold symptoms: watery eyes and runny nose.

Reversible Noncompetitive Inhibition A noncompetitive enzyme inhibitor is a molecule that decreases enzyme activity by binding to a site on an enzyme other than the active site. The substrate can still occupy the active site, but the presence of the inhibitor causes a change in the structure of the enzyme sufficient to prevent the catalytic groups at the active site from properly effecting their catalyzing action. Figure 21.11 contrasts the processes of reversible competitive inhibition and reversible noncompetitive inhibition. Unlike the situation in competitive inhibition, increasing the concentration of substrate does not completely overcome the inhibitory effect in this case. However, lowering the concentration of a noncompetitive inhibitor sufficiently does free up many enzymes, which then return to normal activity. Examples of noncompetitive inhibitors include the heavy metal ions Pb2⫹, Ag⫹, and 2⫹ Hg . The binding sites for these ions are sulfhydryl (9SH) groups located away from the active site. Metal sulfide linkages are formed, an effect that disrupts secondary and tertiary structure.

Irreversible Inhibition An irreversible enzyme inhibitor is a molecule that inactivates enzymes by forming a strong covalent bond to an amino acid side-chain group at the enzyme’s active site. In general, such inhibitors do not have structures similar to that of the enzyme’s normal substrate. The inhibitor–active site bond is sufficiently strong that addition of excess substrate does not reverse the inhibition process. Thus the enzyme is permanently deactivated. The actions of chemical warfare agents (nerve gases) and organophosphate insecticides are based on irreversible inhibition. The Chemistry at a Glance feature on page 712 summarizes what we have considered concerning enzyme inhibition. Figure 21.11 The difference between

Normal substrate

a reversible competitive inhibitor and a reversible noncompetitive inhibitor.

Enzyme

Competitive inhibitor

Enzyme

Normal substrate

Enzyme

Noncompetitive inhibitor (a) An enzyme–substrate complex in absence of an inhibitor.

(b) A competitive inhibitor binds to the active site, which prevents the normal substrate from binding to the site.

(c) A noncompetitive inhibitor binds to a site other than the active site; the normal substrate still binds to the active site but the enzyme cannot catalyze the reaction due to the presence of the inhibitor.

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Chapter 21 Enzymes and Vitamins

Enzyme Inhibition ENZYME INHIBITORS Substances that bind to an enzyme and stop or slow its normal catalytic activity

Competitive Enzyme Inhibitor

Noncompetitive Enzyme Inhibitor

Irreversible Enzyme Inhibitor

A molecule closely resembling the substrate. Binds to the active site and temporarily prevents substrates from occupying it, thus blocking the reaction. Competitive Substrate inhibitor

A molecule that binds to a site on an enzyme that is not the active site. The normal substrate still occupies the active site but the enzyme cannot catalyze the reaction due to the presence of the inhibitor. Substrate

A molecule that forms a covalent bond to a part of the active site, permanently preventing substrates from occupying it.

Substrate

Irreversible inhibitor Enzyme active site

Enzyme

Noncompetitive inhibitor

EXERCISE 21.4 Identifying the Type of Enzyme Inhibition from Inhibitor Characteristics

Identify the type of enzyme inhibition each of the following inhibitor characteristics is associated with. a. An inhibitor that decreases enzyme activity by binding to a site on the enzyme other than the active site b. An inhibitor that inactivates enzymes by forming a strong covalent bond at the enzyme active site Solution

a. Inhibitor binding at a nonactive site location is a characteristic of a reversible noncompetitive inhibitor. b. Covalent bond formation at the active site, with amino acid residues located there, is a characteristic of an irreversible inhibitor.

Practice Exercise 21.4 Identify the type of enzyme inhibition each of the following inhibitor characteristics is associated with. a. An inhibitor that has a shape and charge distribution similar to that of the enzyme’s normal substrate b. An inhibitor whose effect can be reduced by simply increasing the concentrate of normal substrate present Answers: a. Reversible competitive inhibitor; b. Reversible competitive inhibitor

21.8 Regulation of Enzyme Activity

713

21.8 REGULATION OF ENZYME ACTIVITY Regulation of enzyme activity within a cell is a necessity for many reasons. Illustrative of this need are the following two situations, both of which involve the concept of energy conservation. 1. A cell that continually produces large amounts of an enzyme for which substrate concentration is always very low is wasting energy. The production of the enzyme needs to be “turned off.” 2. A product of an enzyme-catalyzed reaction that is present in plentiful (more than needed) amounts in a cell, is a waste of energy if the enzyme continues to catalyze the reaction that produces the product. The enzyme needs to be “turned off.” Many mechanisms exist by which enzymes within a cell can be “turned on” and “turned off.” In this section we consider, in general terms, three such mechanisms: (1) feedback control associated with allosteric enzymes, (2) proteolytic enzymes and zymogens, and (3) covalent modification.

Allosteric Enzymes Many, but not all, of the enzymes responsible for regulating cellular processes are allosteric enzymes. Characteristics of allosteric enzymes are as follows: 1. All allosteric enzymes have quaternary structure; that is, they are composed of two or more protein chains. 2. All allosteric enzymes have two kinds of binding sites: those for substrate and those for regulators. 3. Active and regulatory binding sites are distinct from each other in both location and shape. Often the regulatory site is on one protein chain and the active site is on another. 4. Binding of a molecule at the regulatory site causes changes in the overall threedimensional structure of the enzyme, including structural changes at the active site. The term allosteric comes from the Greek allo, which means “other,” and stereos, which means “site or space.”

Some regulators of allosteric enzyme function are inhibitors (negative regulators), and some increase enzyme activity (positive regulators).

Most biochemical processes within cells take place in several steps rather than in a single step. A different enzyme is required for each step of the process. Feedback control is operative in devices that maintain a constant temperature, such as a furnace or an oven. If you set the control thermostat at 68⬚F, the furnace or oven produces heat until that temperature is reached, and then, through electronic feedback, the furnace or oven is shut off.

Thus an allosteric enzyme is an enzyme with two or more protein chains (quaternary structure) and two kinds of binding sites (substrate and regulator). Substances that bind at regulatory sites of allosteric enzymes are called regulators. The binding of a positive regulator increases enzyme activity; the shape of the active site is changed such that it can more readily accept substrate. The binding of a negative regulator (a noncompetitive inhibitor) decreases enzyme activity; changes to the active site are such that substrate is less readily accepted. Figure 21.12 contrasts the different effects on an allosteric enzyme that positive and negative regulators produce.

Feedback Control One of the mechanisms by which allosteric enzyme activity is regulated is feedback control. Feedback control is a process in which activation or inhibition of the first reaction in a reaction sequence is controlled by a product of the reaction sequence. To illustrate the feedback control mechanism, let us consider a biochemical process within a cell that occurs in several steps, each step catalyzed by a different enzyme. Enzyme 1

Enzyme 2

Enzyme 3

A 788888n B 788888n C 788888n D

The product of each step is the substrate for the next enzyme. What will happen in this reaction series if the final product (D) is a negative regulator of the first enzyme (enzyme 1)? At low concentrations of D, the reaction sequence proceeds rapidly. At higher concentrations of D, the activity of enzyme 1 becomes inhibited (by feedback), and eventually the activity stops. At the stopping point, there is sufficient D present in the cell to meet its needs. Later, when the concentration of D decreases through use in other cell reactions, the activity of enzyme 1 increases and more D is produced.

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Chapter 21 Enzymes and Vitamins

Figure 21.12 The differing effects of positive and negative regulators on an allosteric enzyme.

Negative Allosteric Control Active site

Negative allosteric regulator

Substrate cannot enter

Substrate

Allosteric site

Positive Allosteric Control Unavailable active site

Substrate can enter

Positive allosteric regulator

g

Feedback control Inhibition of enzyme 1 by product D

Enzyme 1

Enzyme 2

Enzyme 3

A 788888n B 788888n C 788888n D The general term allosteric control is often used to describe a process in which a regulatory molecule that binds at one site in an enzyme influences substrate binding at the active site in the enzyme.

The names of zymogens can be recognized by the suffix -ogen or the prefix pre- or pro-.

Feedback control is not the only mechanism by which an allosteric enzyme can be regulated; it is just one of the more common ways. Regulators of a particular allosteric enzyme may be products of entirely different pathways of reaction within the cell, or they may even be compounds produced outside the cell (hormones).

Proteolytic Enzymes and Zymogens A second mechanism for regulating cellular enzyme activity is based on the production of enzymes in an inactive form. These inactive enzyme precursors are then “turned on” at the appropriate time. Such a mechanism for control is often encountered in the production of proteolytic enzymes. A proteolytic enzyme is an enzyme that catalyzes the breaking of peptide bonds that maintain the primary structure of a protein. Because they would otherwise destroy the tissues that produce them, proteolytic enzymes are generated in an inactive form and then later, when they are needed, are converted to their active form. Most digestive and blood-clotting enzymes are proteolytic enzymes. The inactive forms of proteolytic enzymes are called zymogens. A zymogen is the inactive precursor of a proteolytic enzyme. (An alternative, but less often used, name for a zymogen is proenzyme.) Activation of a zymogen requires an enzyme-controlled reaction that removes some part of the zymogen structure. Such modification changes the three-dimensional structure (secondary and tertiary structure) of the zymogen, which affects active site conformation. For example, the zymogen pepsinogen is converted to the active enzyme pepsin in the stomach, where it then functions as a digestive enzyme. Pepsin would digest

21.9 Antibiotics That Inhibit Enzyme Activity

Figure 21.13 Conversion of a zymogen (the inactive form of a proteolytic enzyme) to a proteolytic enzyme (the active form of the enzyme) often involves removal of a peptide chain segment from the zymogen structure.

Peptide fragment to be removed

S

S

S

S

S

S

715

S

S

Activation Zymogen (inactive form of a proteolytic enzyme)

Proteolytic enzyme (an active enzyme)

the tissues of the stomach wall if it were prematurely generated in active form. Pepsinogen activation involves removal of a peptide fragment from its structure (Figure 21.13).

Covalent Modification of Enzymes A third mechanism for regulation of enzyme activity within a cell, called covalent modification, involves adding or removing a group from an enzyme through the forming or breaking of a covalent bond. Covalent modification is a process in which enzyme activity is altered by covalently modifying the structure of the enzyme through attachment of a chemical group to or removal of a chemical group from a particular amino acid within the enzyme’s structure. The most commonly encountered type of covalent modification involves the processes by which a phosphate group is added to or removed from an enzyme. The source of the added phosphate group is often an ATP molecule. The process of addition of the phosphate group to the enzyme is called phosphorylation and the removal of the phosphate group from the enzyme is called dephosphorylation. This phosphorylation/dephosphorylation process is the off/on or on/off switch for the enzyme. For some enzymes the active (“turned-on” form) is the phosphorylated version of the enzyme; however, for other enzymes it is the dephosphorylated version that is active. The preceding covalent modification processes are governed by other enzymes. Protein kinases effect the addition of phosphate groups and phosphatases catalyze removal of the phosphate groups. Usually, the phosphate group is added to (or removed from) the R group of a serine, tyrosine, or threonine amino acid residue present in the protein (enzyme). The R groups of these three amino acids have a common structural feature, the presence of a free 9OH group (see Table 21.1). The hydroxyl group is the site where phosphorylation or dephosphorylation occurs. Glycogen phosphorylase, an enzyme involved in the breakdown of glycogen to glucose (Section 24.5) is activated by the addition of a phosphate group. Glycogen synthase, an enzyme involved in the synthesis of glycogen (Section 24.5) is deactivated by phosphorylation.

21.9 ANTIBIOTICS THAT INHIBIT ENZYME ACTIVITY An antibiotic is a substance that kills bacteria or inhibits their growth. Antibiotics exert their action selectively on bacteria and do not affect the normal metabolism of the host organism. Antibiotics usually inhibit specific enzymes essential to the life processes of bacteria. In this section we consider the actions of two families of antibiotics, sulfa drugs and penicillins, as well as the specific antibiotic Cipro.

Sulfa Drugs The 1932 discovery of the antibacterial activity of the compound sulfanilamide by the German bacteriologist Gerhard Domagk (1895–1964) led to the characterization of a whole family of sulfanilamide derivatives collectively called sulfa drugs—the first “antibiotics” in the medical field.

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Chapter 21 Enzymes and Vitamins

Figure 21.14 Structures of selected sulfa drugs in use today as antibiotics.

General Structure of Sulfa Drugs O H2N

S

R Group Variations in Sulfa Drug Structures R=

NH

R

O

Sulfanilamide

H O

R=

Sulfacetamide

CH3

C O

R= CH3

Increasing effectiveness against E. coli bacteria

Sulfisoxazole

N CH3

N

Sulfadiazine

R= N O

CH3

Sulfadimethoxine

N

R= N

O

CH3

Sulfanilamide inhibits bacterial growth because it is structurally similar to PABA ( p-aminobenzoic acid).

H2N

O B SO NH2 B O Sulfanilamide

H2N

O B CO OH p-Aminobenzoic acid (PABA)

Many bacteria need PABA in order to produce an important coenzyme, folic acid. Sulfanilamide acts as a competitive inhibitor to enzymes in the biosynthetic pathway for converting PABA into folic acid in these bacteria. Folic acid deficiency retards growth of the bacteria and can eventually kill them. Sulfa drugs selectively inhibit only bacteria metabolism and growth because humans absorb folic acid from their diet and thus do not use PABA for its synthesis. A few of the most common sulfa drugs and their structures are shown in Figure 21.14.

Penicillins Penicillin, one of the most widely used antibiotics, was accidentally discovered by Alexander Fleming in 1928 while he was working with cultures of an infectious staphylococcus bacterium. A decade later, the scientists Howard Flory and Ernst Chain isolated penicillin in pure form and proved its effectiveness as an antibiotic. Several naturally occurring penicillins have now been isolated, and numerous derivatives of these substances have been synthetically produced. All have structures containing a four-membered b-lactam ring (Section 17.12) fused with a five-membered thiazolidine ring (Figure 21.15). As with sulfa drugs, derivatives of the basic structure differ from each other in the identity of a particular R group. Penicillins inhibit transpeptidase, an enzyme that catalyzes the formation of peptide cross links between polysaccharide strands in bacterial cell walls. These cross links strengthen cell walls. A strong cell wall is necessary to protect the bacterium from lysis (breaking open). By inhibiting transpeptidase, penicillin prevents the formation of a strong cell wall. Any osmotic or mechanical shock then causes lysis, killing the bacterium. Penicillin’s unique action depends on two aspects of enzyme deactivation that we have discussed before: structural similarity to the enzyme’s natural substrate and irreversible inhibition. Penicillin is highly specific in binding to the active site of transpeptidase. In this sense, it acts as a very selective competitive inhibitor. However, unlike a normal competitive inhibitor, once bound to the active site, the b-lactam ring opens as the highly reactive amide bond forms a covalent bond to a critical serine residue required for normal catalytic action. The result is an irreversibly inhibited transpeptidase enzyme (Figure 21.16).

21.9 Antibiotics That Inhibit Enzyme Activity

Figure 21.15 Structures of selected penicillins in use today as antibiotics.

General Structure of Penicillin

R Group Variations in Penicillin Structures

␤ -lactam ring O R

C

NH

S

R=

CH2

R=

O

Penicillin G (benzyl penicillin)

CH3 CH3

N

O

717

COOH

Thiazolidine ring Reactive amide bond

CH2

O

CH3

O

CH3

Methicillin

R=

R=

CH

Ampicillin

NH2 R=

Penicillin V

HO

CH

Amoxicillin

NH2 R= N

Oxacillin O

CH3

Some bacteria produce the enzyme penicillinase, which protects them from penicillin. Penicillinase selectively binds penicillin and catalyzes the opening of the b-lactam ring before penicillin can form a covalent bond to the enzyme. Once the ring is opened, the penicillin is no longer capable of inactivating transpeptidase. Certain semi-synthetic penicillins such as methicillin and amoxicillin have been produced that are resistant to penicillinase activity and are thus clinically important. Penicillin does not usually interfere with normal metabolism in humans because of its highly selective binding to bacterial transpeptidase. This selectivity makes penicillin an extremely useful antibiotic.

Cipro The antibiotic ciprofloxacin hydrochloride (marketed as “Cipro”) is an effective agent against bacterial infections in many different parts of the body. It is effective against skin and bone infections as well as against infections involving the urinary, gastrointestinal, and respiratory systems. It is the drug of choice for treatment of traveler’s diarrhea. It is considered one of the best broad-spectrum antibiotics available. Bacteria are slow to acquire resistance to Cipro. Structurally, Cipro contains several common functional groups (carboxylic acid, ketone, and amine), as well as two seldom-encountered groups (fluoro and cyclopropyl). H

N N

N C

F O R

Figure 21.16 The selective binding of penicillin to the active site of transpeptidase. Subsequent irreversible inhibition through formation of a covalent bond to a serine residue permanently blocks the active site.

O

OH

Penicillin

R O

C NH

S

O

CH3

H

O

COOH

CH2

Serine residue

C NH

CH3

C N O

O

Covalent bond formation

S C N O

H

CH2

CH3 CH3 COOH

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Chapter 21 Enzymes and Vitamins

TABLE 21.3 Selected Blood Enzyme Assays Used in Diagnostic Medicine

Enzyme

Condition Indicated by Abnormal Level

lactate dehydrogenase (LDH) creatine phosphokinase (CPK) aspartate transaminase (AST) alanine transaminase (ALT) gamma-glutamyl transpeptidase (GGTP) alkaline phosphatase (ALP)

heart disease, liver disease heart disease heart disease, liver disease, muscle damage heart disease, liver disease, muscle damage heart disease, liver disease bone disease, liver disease

Concern about biochemical threats associated with terrorism has thrust Cipro into the spotlight because it is effective against anthrax. As early as 1990, the U.S. Department of Defense began stockpiling doses of Cipro; the government’s 2001 order was 100 million doses. Cipro is not the only antianthrax drug available. The FDA recommends the use of doxycycline as the first-line treatment for anthrax because this compound can deal with all the strains of anthrax that are currently encountered. Authorities would rather keep Cipro in reserve; widespread current use of the drug could speed up the evolution of drug-resistant organisms. Cipro is believed to attack the enzyme DNA gyrase, which controls how DNA in a bacterial chromosome coils into its tertiary structure. When tertiary structure is disrupted, replication and transcription of the DNA cannot occur.

21.10 MEDICAL USES OF ENZYMES

Figure 21.17 Drawing of a blood sample. Determination of enzyme concentrations in blood provides important information about the “state” of various organs within the human body.

Enzymes can be used to diagnose certain diseases. Although blood serum contains many enzymes, some enzymes are not normally found in the blood but are produced only inside cells of certain organs and tissues. The appearance of these enzymes in the blood often indicates that there is tissue damage in an organ and that cellular contents are spilling out (leaking) into the bloodstream (see Figure 21.17). Assays of abnormal enzyme activity in blood serum can be used to diagnose many disease states, some of which are listed in Table 21.3. The Chemical Connections feature on page 719 examines the use of enzymes to diagnose heart attacks (myocardial infarctions). Enzymes can also be used in the treatment of diseases. A recent advance in treating heart attacks is the use of tissue plasminogen activator (TPA), which activates the enzyme plasminogen. When so activated, this enzyme dissolves blood clots in the heart and often provides immediate relief. Another medical use for enzymes is in clinical laboratory chemical analysis. For example, no simple direct test for the measurement of urea in the blood is available. However, if the urea in the blood is converted to ammonia via the enzyme urease, the ammonia produced, which is easily measured, becomes an indicator of urea. This blood urea nitrogen (BUN) test is a common clinical laboratory procedure. High urea levels in the blood indicate kidney malfunction.

21.11 GENERAL CHARACTERISTICS OF VITAMINS This section and the two that follow deal with vitamins. Vitamins are considered in conjunction with enzymes because many enzymes contain vitamins as part of their structure. Recall from Section 21.2 that conjugated enzymes have a protein part (apoenzyme) and a nonprotein part (cofactor). Vitamins, in many cases, are cofactors in conjugated enzymes. A vitamin is an organic compound, essential in small amounts for the proper functioning of the human body, that must be obtained from dietary sources because the body cannot synthesize it.

21.11 General Charactaristics of Vitamins

c

719

HEMICAL

Heart Attacks and Enzyme Analysis

Tissue brain heart kidney liver lung serum skeletal muscle

LDH1 23 50 28 4 10 28 5

LDH2 34 36 34 6 20 41 5

The spelling of the term vitamin was originally vitamine, a word derived from the Latin vita, meaning “life,” and from the fact that these substances were all thought to contain the amine functional group. When this supposition was found to be false, the final e was dropped from vitamine, and the term vitamin came into use. Some vitamins contain amine functional groups, but others do not.

LDH3

LDH4

LDH5

30 9 21 17 30 19 10

10 3 11 16 25 7 22

3 2 6 57 15 5 58

CPK Enzyme level

The symptoms of a heart attack—that is, a myocardial infarction (MI)—include irregular breathing and pain in the left chest that may radiate to the neck, left shoulder, and arm. An initial diagnosis of an MI is based on these and other physical symptoms, and treatment is initiated on this basis. Physicians then use enzyme analysis to confirm the diagnosis and to monitor the course of treatment. The blood levels of three enzymes are commonly assayed in MI situations: creatine phosphokinase (CPK), aspartate transaminase (AST), and lactate dehydrogenase (LDH). The CPK level rises and falls relatively rapidly after a heart attack, reaching a maximum after about 30 hours at a level approximately six times normal. The AST level triples after about 40 hours. LDH, whose concentrations rise slowly, is used to monitor the later stages of the MI and to assess the extent of heart damage. The accompanying graph shows blood levels of these three enzymes as a function of time in an MI situation. Further information about the seriousness of an MI is obtained by studying isoenzymes. Isoenzymes are forms of the same enzyme with slightly different amino acid sequences. The use of the prefix “iso” in the term isoenzymes implies that such enzymes catalyze the “same” reaction and not that they have isomeric structures. Lactate dehydrogenase is a mixture of five isoenzymes denoted LDH1 to LDH5. Creatine phosphokinase is a mixture of three isoenzymes denoted CK-MM, CK-MB, and CK-BB. Consideration of further details about the LDH isoenzymes shows how isoenzymes give information about whether a heart attack has occurred or not. Note from the following table that heart tissue is particularly high in LDH1 and that liver and skeletal muscle are particularly high in LDH5.

AST LDH

24

48

72

96 Hours

120

144

168

When a heart attack occurs, some heart muscle cells are damaged (destroyed), and their enzymes “leak” into the bloodstream. This changes the ratios among the various LDHs present in blood, because heart muscle is particularly high in LDH1. The accompanying graph of an LDH isoenzyme assay for a heart attack victim shows that the LDH1/LDH2 ratio, which is normally less than one in blood serum, is now greater than one.

Normal LDH levels Patient’s LDH levels LDH concentration

onnections

LDH1/LDH2 ratio is less than 1.

Admission

LDH1/LDH2 ratio is greater than 1.

6–13 hours after admission

24–37 hours after admission

Vitamins differ from the major classes of foods (carbohydrates, lipids, and proteins) in the amount required; for vitamins it is microgram or milligram quantities per day compared with 50–200 grams per day for the major food categories. To illustrate the small amount of vitamins needed by the human body, consider the recommended daily allowance (RDA) of vitamin B12, which is 2.0 micrograms per day for an adult. Just 1.0 gram of this vitamin could theoretically supply the daily needs of 500,000 people. A well-balanced diet usually meets all the body’s vitamin requirements. However, supplemental vitamins are often required for women during pregnancy and for people recovering from certain illnesses. One of the most common myths associated with the nutritional aspects of vitamins is that vitamins from natural sources are superior to synthetic vitamins. In truth, synthetic

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Chapter 21 Enzymes and Vitamins

TABLE 21.4 The Water-Soluble and Fat-Soluble Vitamins

Water-Soluble Vitamins

Fat-Soluble Vitamins

Thiamin Riboflavin Niacin Vitamin B6 Folate Vitamin B12 Pantothenic acid Biotin Vitamin C

Vitamin A Vitamin D Vitamin E Vitamin K

vitamins, manufactured in the laboratory, are identical to the vitamins found in foods. The body cannot tell the difference and gets the same benefits from either source. There are 13 known vitamins, and scientists believe that the discovery of additional vitamins is unlikely. Despite searches for new vitamins, it has been over 50 years since the last of the known vitamins (B12) was discovered. Strong evidence that the vitamin family is complete comes from the fact that many people have lived for years being fed, intravenously, solutions containing the known vitamins and nutrients, and they have not developed any known vitamin deficiency disease. Solubility characteristics divide the vitamins into two major classes: the water-soluble vitamins and the fat (lipid)-soluble vitamins. There are nine water-soluble vitamins and four fat-soluble vitamins. Table 21.4 gives the identity of the vitamins that fall in each of these solubility categories. Water-soluble vitamins must be constantly replenished in the body because they are rapidly eliminated from the body in the urine. They are carried in the bloodstream, are needed in frequent, small doses, and are unlikely to be toxic except when taken in unusually large doses. The fat-soluble vitamins are found dissolved in lipid materials. They are, in general, carried in the blood by protein carriers, are stored in fat tissues, are needed in periodic doses, and are more likely to be toxic when consumed in excess of need. An important difference exists, in terms of function, between water-soluble and fatsoluble vitamins. Water-soluble vitamins function as coenzymes for a number of important biochemical reactions in humans, animals, and microorganisms. Fat-soluble vitamins generally do not function as coenzymes in humans and animals and are rarely utilized in any manner by microorganisms. Other differences between the two categories of vitamins are summarized in Table 21.5. A few exceptions occur, but the differences shown in this table are generally valid.

TABLE 21.5 The General Properties of Water-Soluble Vitamins and Fat-Soluble Vitamins

Water-Soluble Vitamins (B vitamins and vitamin C)

Fat-Soluble Vitamins (vitamins A, D, E, and K)

absorption

directly into the blood

first enter into the lymph system

transport

travel without carriers

many require protein carriers

storage

circulate in the water-filled parts of the body

found in the cells associated with fat

excretion

kidneys remove excess in urine

tend to remain in fat-storage sites

toxicity

not likely to reach toxic levels when consumed from supplements

likely to reach toxic levels when consumed from supplements

requirements

needed in frequent doses

needed in periodic doses

relationship to coenzymes

function as coenzymes

do not function as coenzymes

21.12 Water-Soluble Vitamins

721

21.12 WATER-SOLUBLE VITAMINS The nine water-soluble vitamins, vitamin C and eight B vitamins, got their names from the labels B and C on the test tubes in which they were first collected. Later, test tube B was found to contain more than one vitamin.

Vitamin C Vitamin C, which has the simplest structure of the 13 vitamins, exists in two active forms in the human body: an oxidized form and a reduced form. CH2 O CH A A OH OH HO

O

O

Oxidation Reduction

OH

Ascorbic acid (reduced)

Vitamin C, the best known of all vitamins, was the first vitamin to be discovered (1928), the first to be structurally characterized (1933), and the first to be synthesized in the laboratory (1933). Laboratory production of vitamin C, which exceeds 80 million pounds per year, is greater than the combined production of all the other vitamins. In addition to its use as a vitamin supplement, synthetic vitamin C is used as a food additive (preservative), a flour additive, and an animal feed additive.

B

F

Other naturally occurring dietary antioxidants include glutathione (Section 20.7), vitamin E (Section 21.13), beta-carotene (Section 21.13), and flavonoids (Section 23.11).

O J O

O M O

⫹ 2H

Dehydroascorbic acid (oxidized)

Humans, monkeys, apes, and guinea pigs are among the relatively few species that require dietary sources of vitamin C. Other species synthesize vitamin C from carbohydrates. Vitamin C’s biosynthesis involves L-gulonic acid, an acid derivative of the monosaccharide L-gulose (see Figure 18.13). L-Gulonic acid is changed by the enzyme lactonase into a cyclic ester (lactone, Section 16.11); ring closure involves carbons 1 and 4. An oxidase then introduces a double bond into the ring, producing L-ascorbic acid.

HO

COOH H

HO

H

H

H HO

Why is vitamin C called ascorbic acid when there is no carboxyl group (acid group) present in its structure? Vitamin C is a cyclic ester in which a carbon 1 carboxyl group has reacted with a carbon 4 hydroxyl group, forming the ring structure.

CH2 O CH A A OH OH

OH H CH2OH

L-Gulonic

acid

Lactonase

CH2OH OH O OH HO H H

H

g-L-Gulonolactone

H O

Oxidase

CH2OH OH O

O

H HO L-Ascorbic

OH acid

The four —OH groups present in vitamin C’s reduced form are suggestive of its biosynthetic monosaccharide (polyhydroxy aldehyde) origins. Its chemical name, L-ascorbic acid, correctly indicates that vitamin C is a weak acid. Although no carboxyl group is present, the carbon 3 hydroxyl group hydrogen atom exhibits acidic behavior as a result of its attachment to an unsaturated carbon atom. The most completely characterized role of vitamin C is its function as a cosubstrate in the formation of the structural protein collagen (Section 20.17), which makes up much of the skin, ligaments, and tendons and also serves as the matrix on which bone and teeth are formed. Specifically, biosynthesis of the amino acids hydroxyproline and hydroxylysine (important in binding collagen fibers together) from proline and lysine requires the presence of both vitamin C and iron. Iron serves as a cofactor in the reaction, and vitamin C maintains iron in the oxidation state that allows it to function. In this role, vitamin C is functioning as a specific antioxidant. Vitamin C also functions as a general antioxidant (Section 14.14) for water-soluble substances in the blood and other body fluids. Its antioxidant properties are also beneficial for several other vitamins. The active form of vitamin E is regenerated by vitamin C, and it also helps keep the active form of folate (a B vitamin) in its reduced state. Because of its antioxidant properties, vitamin C is often added to foods as a preservative. Vitamin C is also involved in the metabolism of several amino acids that end up being converted to the hormones norepinephrine and thyroxine. The adrenal glands contain a higher concentration of vitamin C than any other organ in the body.

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Chapter 21 Enzymes and Vitamins

An intake of 100 mg/day of vitamin C saturates all body tissues with the compound. After the tissues are saturated, all additional vitamin C is excreted. The RDA for vitamin C varies from country to country. It is 30 mg/day in Great Britain, 60 mg/day in the United States and Canada, and 75 mg/day in Germany. A variety of fruits and vegetables have a relatively high vitamin C content (see Figure 21.18).

Vitamin B There are eight B vitamins. Our discussion of them involves four topics: nomenclature, function, structural characteristics, and dietary sources. Much confusion exists about the B vitamins’ names. Many have “number” names as well as “word” names (often several). The preferred names for the B vitamins (alternative names in parentheses) are 1. 2. 3. 4. 5. 6. 7. 8.

Figure 21.18 Rows of cabbage plants. Although many people think citrus fruits (50 mg per 100 g) are the best source of vitamin C, peppers (128 mg per 100 g), cauliflower (70 mg per 100 g), strawberries (60 mg per 100 g), and spinach or cabbage (60 mg per 100 g) are all richer in vitamin C.

B vitamin structure is very diverse. The only common thread among structures is that all structures, except that of pantothenic acid, involve heterocyclic nitrogen ring systems. The element sulfur is present in two structures (thiamin and biotin), and vitamin B12 contains a metal atom (cobalt). (Biotin does not contain a tin atom, as the name might imply.) Table 21.6 gives structural forms for the eight B vitamins. Note that for two B vitamins (niacin and vitamin B6), more than one form of the vitamin exists. The major function of B vitamins within the human body is as components of coenzymes (Section 21.2). Unlike vitamin C, all of the B vitamins must be chemically modified before they become functional within the coenzymes. For example, thiamine is converted to thiamine pyrophosphate (TPP), which then serves as the coenzyme in several reactions involving carbohydrate metabolism.

Pronunciation guidelines for the standard names of the B vitamins: THIGH-ah-min RYE-boh-flay-vin NIGH-a-sin FOLL-ate PAN-toe-THEN-ick acid BY-oh-tin

O⫺ NH2

H3C CH2

N H3C

Thiamin (vitamin B1) Riboflavin (vitamin B2) Niacin (nicotinic acid, nicotinamide, vitamin B3) Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine) Folate (folic acid) Vitamin B12 (cobalamin) Pantothenic acid (vitamin B5) Biotin

N ⫹

CH2

CH2

OH

NH2

S

CH2

N H3 C

N

H3C

CH2

N

CH2

O

O

O

S

⫹

P

O⫺ P

O⫺

O

N

Thiamine (vitamin B1)

Thiamine pyrophosphate (TPP)

Another example of chemical modification for a B vitamin is the conversion of folate to tetrahydrofolate (THF). H N

H2N N

N

H

N

CH2

OH

N H

Folate

N

H2N R

N OH

N

H H

N

H CH2

H

N

R

H

Tetrahydrofolate (THF)

Table 21.7 lists selected important coenzymes that involve B vitamins and indicates how these coenzymes function. In general, coenzymes serve as temporary carriers of atoms or functional groups in redox and group transfer reactions.

21.12 Water-Soluble Vitamins

723

TABLE 21.6 Structures of the Eight B Vitamins Thiamine

Riboflavin

H3C

CH2

CH2

OH

NH2

H3C

N

CH2

N

H3C

N Niacin (two forms)

O B COOH

H

O OH CH3 O B A B A HOOC OCH2 OCH2 ONOC OCH OC O CH2O OH A A H CH3

N

Nicotinic acid

D

Pantothenic Acid

O B CO NH2

N

N

N O N N A CH2 O CH O CH O CH O CH2 A A A A OH OH OH OH

S

⫹

O B

N

H3C

Nicotinamide

Vitamin B6 (three forms)

CH2OH CH2OH

HO H3C

CHO HO

CH2OH

H3C

N Pyridoxine

HO H3C

N Pyridoxal

CH2NH2 CH2OH N Pyridoxamine

Folate

N

H2N N

A OH

N N

CH2 O N A H

O O B B C O N O CH O CH2 OCH2 O C O OH A A H CPO A OH

Vitamin B12

R CH3 H

C

R

CH2 CONH2 CH3

CH3 N

CH2 CONH2

⫹

Co

N CH3

H H CH 2

CN

Biotin

CH2CH2CONH2 ECH3 H HCH3 N HCH N CH ECH2CH2CONH2 3 H H CH CH2CONH2 CH3

S

N

O B OCH2OCH2OCH2 OCH2 OC O OH N

H

H O

CH2 CONH2

In their function as coenzymes, some of the B vitamins do not remain permanently bonded to the apoenzyme (Section 21.2) that they are associated with. This means that they can be repeatedly used by various enzymes. This reuse (recycling) diminishes the need for large amounts of the B vitamins in biochemical systems. Figure 21.19 shows diagrammatically how a vitamin is used and then released in an enzyme-catalyzed reaction.

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Chapter 21 Enzymes and Vitamins

TABLE 21.7 Selected Important Coenzymes in Which B Vitamins Are Present

B Vitamin

Coenzymes

Groups Transferred

thiamine

thiamine pyrophosphate (TPP)

aldehydes

riboflavin

flavin mononucleotide (FMN) flavin adenine dinucleotide (FAD)

hydrogen atoms

niacin

nicotinamide adenine dinucleotide (NAD⫹) nicotinamide adenine dinucleotide phosphate (NADP⫹)

hydride ion (H⫺)

vitamin B6

pyridoxal-5-phosphate (PLP)

amino groups

folate

tetrahydrofolate (THF)

one-carbon groups other than CO2

vitamin B12

5⬘-deoxyadenosylcobalamin

alkyl groups, hydrogen atoms

pantothenic acid

coenzyme A (CoA) acyl carrier protein (ACP)

acyl groups

biotin

biocytin

carbon dioxide

An ample supply of the B vitamins can be obtained from normal dietary intake as long as a variety of foods are consumed. A certain food may be a better source of a particular B vitamin than others; however, there are multiple sources for each of the B vitamins as Table 21.8 shows. Note from Table 21.8 that fruits, in general, are very poor sources of B vitamins and that only certain vegetables are good B vitamin sources. Vitamin B12 is unique among the vitamins in being found almost exclusively in food derived from animals. Legislation that dates back to the 1940s requires that all grain products that cross state lines be enriched in thiamin, riboflavin, and niacin. Folate was added to the legislated enrichment list in 1996 when research showed that folate was essential in the prevention of certain birth defects. Both niacin and folate have been linked positively to improvement in cardiovascular health. Adding prescription-strength, extended-release niacin to cholesterol-lowering statin medications slows the progression of atherosclerosis among people with coronary heart disease and low HDL levels better than statin therapy alone. Additionally, prescription niacin is the most effective treatment currently available to increase low levels of HDL. Another study shows that younger women (26–46 years old) who consume 800 mg of folate per day reduce the risk of developing high blood pressure by almost a third compared to those who consume less than 200 mg/day.

Figure 21.19 Many enzymes require a vitamin-based coenzyme in order to be active. After the catalytic action, the vitamin is released and can be reused.

Active site of enzyme

Vitamin (coenzyme)

Products Substrate

Vitamin (coenzyme)

21.13 Fat-Soluble Vitamins

725

TABLE 21.8 A Summary of Dietary Sources of B Vitamins

Vitamin

Vegetable Group

Fruit Group

Bread, Cereal, Rice, and Pasta Group

Milk, Yogurt, and Cheese Group

watermelon whole and enriched grains

thiamine

milk, cheeses

Meat, Poultry, Fish, Dry Beans, Eggs, and Nuts Group Meats

Dry Beans

Eggs Nuts and Seeds

pork, organ meats

legumes

liver, red meat, poultry, fish

legumes

tuna, chicken, beef, turkey

legumes, peanuts

sunflower seeds

sunflower seeds

riboflavin

mushrooms, asparagus, broccoli, leafy greens

whole and enriched grains

niacin

mushrooms, asparagus, potato

whole and enriched grains, wheat bran

vitamin B6

broccoli, spinach, potato, squash

bananas, whole wheat, watermelon brown rice

chicken, fish, pork, organ meats

soybeans

sunflower seeds

folate

mushrooms, leafy greens, broccoli, asparagus, corn

oranges

organ meats (muscle meats are poor sources)

legumes

sunflower seeds, nuts

fortified grains

milk products

vitamin B12 pantothenic mushrooms, acid broccoli,

whole grains

beef, poultry, fish, shellfish

eggs

egg yolk

meat

legumes

egg yolk

liver (muscle meats are poor sources)

soybeans

egg yolk

avocados biotin

B

F

fortified cereals

yogurt

nuts

21.13 FAT-SOLUBLE VITAMINS Lipids are substances that are not soluble in water but are soluble in nonpolar substances such as fat (Section 19.1). Thus, the four fat-soluble vitamins are a type of lipid. They could have been, but were not, discussed in Chapter 19.

The four fat-soluble vitamins are designated using the letters A, D, E, and K. Many of the functions of the fat-soluble vitamins involve processes that occur in cell membranes. The structures of the fat-soluble vitamins are more hydrocarbon-like, with fewer functional groups than the water-soluble vitamins. Their structures as a whole are nonpolar, which enhances their solubility in cell membranes.

Vitamin A Beta-carotene is a deep yellow (almost orange) compound. If a plant food is white or colorless, it possesses little or no vitamin A activity. Potatoes, pasta, and rice are foods in this category.

Normal dietary intake provides a person with both preformed and precursor forms (provitamin forms) of vitamin A. Preformed vitamin A forms are called retinoids. The retinoids include retinal, retinol, and retinoic acid. CH3

CH3

CH3

CH3

R

R ⫽ CH2OH (Retinol) R ⫽ CHO (Retinal) R ⫽ COOH (Retinoic acid)

CH3 Retinoids

Foods derived from animals, including egg yolks and dairy products, provide compounds (retinyl esters) that are easily hydrolyzed to retinoids in the intestine.

726

B

B

F

F

Chapter 21 Enzymes and Vitamins

The retinoids are terpenes (Section 13.7) in which four isoprene units are present. Beta-carotene has an eight-unit terpene structure.

Beta-carotene cleavage does not always occur in the “middle” of the molecule, so only one molecule of vitamin A is produced. Furthermore, not all beta-carotene is converted to vitamin A, and its absorption is not as efficient as that of vitamin A itself. It is estimated that 6 mg of betacarotene is needed to produce 1 mg of retinol. Unconverted beta-carotene serves as an antioxidant (see Section 13.7), a role independent of its conversion to vitamin A.

Figure 21.20 The quantity of vitamin D synthesized by exposure of the skin to sunlight (ultraviolet radiation) varies with latitude, the length of exposure time, and skin pigmentation. (Darkerskinned people synthesize less vitamin D because the pigmentation filters out ultraviolet light.)

Foods derived from plants provide carotenoids (see the Chemical Connections feature “Carotenoids: A Source of Color” on page 374 in Chapter 13), which serve as precursor forms of vitamin A. The major carotenoid with vitamin A activity is beta-carotene (bcarotene), which can be cleaved to yield two molecules of vitamin A. Cleavage at this point can yield two molecules of vitamin A

CH3

CH3

H3C

HO

3

4

5

CH3

CH3

Beta-carotene is a yellow to red-orange pigment plentiful in carrots, squash, cantaloupe, apricots, and other yellow vegetables and fruits, as well as in leafy green vegetables (where the yellow pigment is masked by green chlorophyll). Vitamin A has four major functions in the body. 1. Vision. In the eye, vitamin A (as retinal) combines with the protein opsin to form the visual pigment rhodopsin (see the Chemical Connections feature “Cis–Trans Isomerism and Vision” on page 371 in Chapter 13). Rhodopsin participates in the conversion of light energy into nerve impulses that are sent to the brain. Although vitamin A’s involvement in the process of vision is its best-known function (“Eat your carrots and you’ll see better”), only 0.1% of the body’s vitamin A is found in the eyes. 2. Regulating Cell Differentiation. Cell differentiation is the process whereby immature cells change in structure and function to become specialized cells. For example, some immature bone marrow cells differentiate into white blood cells and others into red blood cells. In the cellular differentiation process, vitamin A (as retinoic acid) binds to protein receptors; these vitamin A–protein receptor complexes then bind to regulatory regions of DNA molecules. 3. Maintenance of the Health of Epithelial Tissues. Epithelial tissue covers outer body surfaces as well as lining internal cavities and tubes. It includes skin and the linings of the mouth, stomach, lungs, vagina, and bladder. Lack of vitamin A (as retinoic acid) causes such surfaces to become drier and harder than normal. Vitamin A’s role here is related to cellular differentiation involving mucus-secreting cells. 4. Reproduction and Growth. In men, vitamin A participates in sperm development. In women, normal fetal development during pregnancy requires vitamin A. In both cases, it is the retinoic acid form of vitamin A that is needed. Again vitamin A’s role is related to cellular differentiation processes.

Vitamin D The two most important members of the vitamin D family of molecules are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D3 is produced in the skin of humans and animals by the action of sunlight (ultraviolet light) on its precursor molecule, the cholesterol derivative 7-dehydrocholesterol (a normal metabolite of cholesterol found in the skin). Absorption of light energy induces breakage of the 9, 10 carbon bond; a spontaneous isomerization (shifting of double bonds) then occurs (see Figure 21.20). H3C

CH3

H3C

CH3 H3C

9 8

10

CH3

Beta-carotene, a precursor for vitamin A

H3C 1

CH3

CH3

H3C

2

CH3

CH3

CH3

7 6

7-Dehydrocholesterol

UV

CH3 CH3

H3C H3C

9

Spontaneous conversion

10

HO Pre-vitamin D3

CH2 HO Vitamin D3 (cholecalciferol)

CH3 CH3

21.13 Fat-Soluble Vitamins

Vitamin D3 (cholecalciferol) is sometimes called the “sunshine vitamin” because of its synthesis in the skin by sunlight irradiation.

727

Vitamin D2 (ergocalciferol) differs from vitamin D3 only in the side-chain structure. It is produced from the plant sterol ergosterol through the action of light. H3C

R

CH3

H3C

D2 series R⫽

CH3 CH3

D3 series R⫽

CH3

CH2

CH3

HO Vitamin D

Both the cholecalciferol and the ergocalciferol forms of vitamin D must undergo two further hydroxylation steps before the vitamin D becomes fully functional. The first step, which occurs in the liver, adds a 9OH group to carbon 25. The second step, which occurs in the kidneys, adds a 9OH group to carbon 1. H3C

CH3 25

CH3 OH

H3C

CH2 3

HO

1

OH

1,25-Dihydroxyvitamin D3

Milk is enriched in vitamin D by exposure to ultraviolet light. Cholesterol in milk is converted to cholecalciferol (vitamin D) by ultraviolet light.

When it comes to strong bones, calcium won’t do you a lot of good unless you are also getting enough vitamin D. In one study, women consuming 500 IU of vitamin D a day had a 37% lower risk of hip fracture than women consuming only 140 IU daily of vitamin D. Some researchers now recommend a standard of 800–1000 IU per day instead of the long-established standard recommendation for vitamin D of 400 IU per day.

Only a few foods, including liver, fatty fish (such as salmon), and egg yolks, are good natural sources of vitamin D. Such vitamin D is vitamin D3. Foods fortified with vitamin D include milk and margarine. The rest of the body’s vitamin D supplies are made within the body (skin) with the help of sunlight. The principal function of vitamin D is to maintain normal blood levels of calcium ion and phosphate ion so that bones can absorb these ions. Vitamin D stimulates absorption of these ions from the gastrointestinal tract and aids in their retention by the kidneys. Vitamin D triggers the deposition of calcium salts into the organic matrix of bones by activating the biosynthesis of calcium-binding proteins.

Vitamin E There are four forms of vitamin E: alpha-, beta-, delta-, and gamma-tocopherol. These forms differ from each other structurally in what substituents (9CH3 or 9H) are present at two positions on an aromatic ring. HO

R⬘⬘ CH3 O

R' CH3 The word tocopherol is pronounced “tuh-KOFF-er-ol.”

CH3

CH3

CH3 CH3

Tocopherols

R⬘ R⬘⬘ ␣ CH3 CH3 ␤ CH3 H ␥ H CH3 ␦ H H

The tocopherol form with the greatest biochemical activity is alpha-tocopherol, the vitamin E form in which methyl groups are present at both the R and R⬘ positions on

728

Chapter 21 Enzymes and Vitamins

the aromatic ring. Gamma-tocopherol is the main form of vitamin E in vitamin-E rich foods. Plant oils (margarine, salad dressings, and shortenings), green and leafy vegetables, and whole-grain products are sources of vitamin E. The primary function of vitamin E in the body is as an antioxidant—a compound that protects other compounds from oxidation by being oxidized itself. Vitamin E is particularly important in preventing the oxidation of polyunsaturated fatty acids (Section 19.2) in membrane lipids. It also protects vitamin A from oxidation. Vitamin E’s antioxidant action involves it giving up the hydrogen present on its 9OH group to oxygencontaining free radicals. After vitamin E is “spent” as an antioxidant, reaction with vitamin C restores the hydrogen atom previously lost by the vitamin E. A most important location in the human body where vitamin E exerts its antioxidant effect is the lungs, where exposure of cells to oxygen (and air pollutants) is greatest. Both red and white blood cells that pass through the lungs, as well as the cells of the lung tissue itself, benefit from vitamin E’s protective effect. Infants, particularly premature infants, do not have a lot of vitamin E, which is passed from the mother to the infant only in the last weeks of pregnancy. Often, premature infants require oxygen supplementation for the purpose of controlling respiratory distress. In such situations, vitamin E is administered to the infant along with oxygen to give antioxidant protection. Vitamin E has also been found to be involved in the conversion of arachidonic acid (20:4) to prostaglandins (Section 19.13).

Vitamin E is unique among the vitamins in that antioxidant activity is its principal biochemical role.

Vitamin K Like the other fat-soluble vitamins, vitamin K has more than one form. Structurally, all forms have a methylated napthoquinone structure to which a long side chain of carbon atoms is attached.The various forms differ structurally in the length and degree of unsaturation of the side chain. O

CH3

R (long carbon chain)

O Vitamin K

Vitamin K1, also called phylloquinone, has a side chain that is predominantly saturated; only one carbon–carbon double bond is present. It is a substance found in plants. Vitamin K2 has several forms, called menaquinones, with the various forms differing in the length of the side chain. Menaquinone side chains have several carbon–carbon double bonds, in contrast to the one carbon–carbon double bond present in phylloquinone. Vitamin K2 is found in animals and humans and can be synthesized by bacteria, including those found in the human intestinal tract. O B

O B

CH3

CH3

CH3 B O

3

CH3 Vitamin K1 (phylloquinone)

CH3

CH3 B O

n

CH3

CH3

(where n may be 1 to 13 but is mostly 7 to 9)

Vitamin K2 (menaquinone)

Typically, about half of the human body’s vitamin K is synthesized by intestinal bacteria and half comes from the diet. Menaquinones are the form of vitamin K found in vitamin K supplements. Only leafy green vegetables such as spinach and cabbage are particularly rich in vitamin K. Other vegetables such as peas and tomatoes and animal tissues, including liver, contain lesser amounts.

Key Reactions and Equations

B

F

All of the fat-soluble vitamins share a common structural feature; they all have terpenelike structures. That is, they are all made up of five-carbon isoprene units (Section 13.5). No common structural pattern exists for the water-soluble vitamins. On the other hand, the water-soluble vitamins have functional uniformity, whereas the fat-soluble vitamins have diverse functions.

c

Vitamin K is essential to the blood-clotting process. Over a dozen different proteins and the mineral calcium are involved in the formation of a blood clot. Vitamin K is essential for the formation of prothrombin and at least five other proteins involved in the regulation of blood clotting. Vitamin K is sometimes given to presurgical patients to ensure adequate prothrombin levels and prevent hemorrhaging. Vitamin K is also required for the biosynthesis of several other proteins found in the plasma, bone, and kidney.

O N C E P TS TO R E M E M B E R

Enzymes. Enzymes are highly specialized protein molecules that act

as biochemical catalysts. Enzymes have common names that provide information about their function rather than their structure. The suffix -ase is characteristic of most enzyme names (Section 21.1). Enzyme structure. Simple enzymes are composed only of protein (amino acids). Conjugated enzymes have a nonprotein portion (cofactor) in addition to a protein portion (apoenzyme). Cofactors may be small organic molecules (coenzymes) or inorganic ions (Section 21.2). Enzyme classification. There are six classes of enzymes based on function: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases (Section 21.3). Enzyme active site. An enzyme active site is the relatively small part of the enzyme that is actually involved in catalysis. It is where substrate binds to the enzyme (Section 21.4). Lock-and-key model of enzyme activity. The active site in an enzyme has a fixed, rigid geometrical conformation. Only substrates with a complementary geometry can be accommodated at the active site (Section 21.4). Induced-fit model of enzyme activity. The active site in an enzyme can undergo small changes in geometry in order to accommodate a series of related substrates (Section 21.4). Enzyme activity. Enzyme activity is a measure of the rate at which an enzyme converts substrate to products. Four factors that affect enzyme activity are temperature, pH, substrate concentration, and enzyme concentration (Section 21.6). Enzyme inhibition. An enzyme inhibitor slows or stops the normal catalytic function of an enzyme by binding to it. Three modes of

k

729

inhibition are reversible competitive inhibition, reversible noncompetitive inhibition, and irreversible inhibition (Section 21.7). Allosteric enzyme. An allosteric enzyme is an enzyme with two or more protein chains and two kinds of binding sites (for substrate and regulator) (Section 21.8). Zymogen. A zymogen is an inactive precursor of a proteolytic enzyme; the zymogen is activated by a chemical reaction that removes to part of its structure (Section 21.8). Covalent modification. Covalent modification is a cellular process for regulation of enzyme activity in which the structure of an enzyme is modified through formation of, or breaking of, a covalent bond. The most commonly encountered type of covalent modification involves a phosphate group being added to, or removed from, an enzyme (Section 21.8). Vitamins. A vitamin is an organic compound necessary in small amounts for the normal growth of humans and some animals. Vitamins must be obtained from dietary sources because they cannot be synthesized in the body (Section 21.11). Water-soluble vitamins. Vitamin C and the eight B vitamins are the water-soluble vitamins. Vitamin C is essential for the proper formation of bones and teeth and is also an important antioxidant. All eight B vitamins function as coenzymes (Section 21.12). Fat-soluble vitamins. The four fat-soluble vitamins are vitamins A, D, E, and K. The best-known function of vitamin A is its role in vision. Vitamin D is essential for the proper use of calcium and phosphorus to form bones and teeth. The primary function of vitamin E is as an antioxidant. Vitamin K is essential in the regulation of blood clotting (Section 21.13).

EY R E A C T I O N S A N D E Q U AT I O N S

1. Conversion of an apoenzyme to an active enzyme (Section 21.2) Apoenzyme ⫹ cofactor ¡ holoenzyme (active enzyme) 2. Mechanism of enzyme action (Section 21.4) Enzyme ⫹ substrate ¡ enzyme–substrate complex Enzyme–substrate complex ¡ enzyme ⫹ product

3. Enzyme inhibition (Section 21.7) Enzyme ⫹ inhibitor ¡ inactive enzyme

730

Chapter 21 Enzymes and Vitamins

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Importance of Enzymes (Section 21.1) 21.1 What is the general role of enzymes in the human body? 21.2 Why does the body need so many different enzymes? 21.3 List two ways in which enzymes differ from inorganic

laboratory catalysts. 21.4 Occasionally we refer to the “delicate” nature of enzymes. Explain why this adjective is appropriate. Enzyme Structure (Section 21.2) 21.5 Indicate whether each of the following phrases describes a simple or a conjugated enzyme. a. An enzyme that has both a protein and a nonprotein portion b. An enzyme that requires Mg2⫹ ion for activity c. An enzyme in which only amino acids are present d. An enzyme in which a cofactor is present 21.6 Indicate whether each of the following phrases describes a simple or a conjugated enzyme. a. An enzyme that contains a carbohydrate portion b. An enzyme that contains only protein c. A holoenzyme d. An enzyme that has a vitamin as part of its structure 21.7 What is the difference between a cofactor and a coenzyme? 21.8 All coenzymes are cofactors, but not all cofactors are coen-

zymes. Explain this statement.

21.9 Why are cofactors present in most enzymes? 21.10 What is the difference between an apoenzyme and a

holoenzyme?

21.18 Give the name of the substrate on which each of the following

enzymes acts. a. Cytochrome oxidase c. Succinate dehydrogenase

21.19 To which of the six major classes of enzymes does each of the

following belong? a. Mutase b. Dehydratase c. Carboxylase d. Kinase 21.20 To which of the six major classes of enzymes does each of the following belong? a. Protease b. Racemase c. Dehydrogenase d. Synthetase 21.21 To which of the six major classes of enzymes does the enzyme

that catalyzes each of the following reactions belong? a. A cis double bond is converted to a trans double bond. b. An alcohol is dehydrated to form a compound with a double bond. c. An amino group is transferred from one substrate to another. d. An ester linkage is hydrolyzed. 21.22 To which of the six major classes of enzymes does the enzyme that catalyzes each of the following reactions belong? a. An L isomer is converted to a D isomer. b. A phosphate group is transferred from one substrate to another. c. An amide linkage is hydrolyzed. d. Hydrolysis of a carbohydrate to monosaccharides occurs. 21.23 Identify the enzyme needed in each of the following reactions

Enzyme Nomenclature (Section 21.3) 21.11 Which of the following substances are enzymes? a. Sucrase b. Galactose c. Trypsin d. Xylulose reductase 21.12 Which of the following substances are enzymes? a. Sucrose b. Pepsin c. Glutamine synthetase d. Cellulase

as an isomerase, a decarboxylase, a dehydrogenase, a lipase, or a phosphatase. a. O O B B CH3OCOH ⫹ CO2 CH3OCOCOOH b.

21.13 Predict the function of each of the following enzymes.

21.15 Suggest a name for an enzyme that catalyzes each of the

following reactions. a. Hydrolysis of sucrose b. Decarboxylation of pyruvate c. Isomerization of glucose d. Removal of hydrogen from lactate 21.16 Suggest a name for an enzyme that catalyzes each of the following reactions. a. Hydrolysis of lactose b. Oxidation of nitrite c. Decarboxylation of citrate d. Reduction of oxalate 21.17 Give the name of the substrate on which each of the following

b. Galactase d. L-Amino acid reductase

O B CH2 OOOC O R O B CHOOOC O R ⫹ 3H2O

a. Pyruvate carboxylase b. Alcohol dehydrogenase d. Maltase c. L-Amino acid reductase 21.14 Predict the function of each of the following enzymes. a. Cytochrome oxidase b. Cis–trans isomerase c. Succinate dehydrogenase d. Lactase

enzymes acts. a. Pyruvate carboxylase c. Alcohol dehydrogenase

b. Lactase d. Tyrosine kinase

O B CH2 OOOC O R

CH2 OOH A CHO OH ⫹ 3RO COOH A CH2 OOH

⫹

c. H3N OCHO COO⫺ ⫹ H2O A CH2 A OPO32⫺ ⫹ H3N OCHO COO⫺ ⫹ HPO42⫺ A CH2 A OH d.

OH A CH3O CHOCOOH ⫹ NAD⫹ O B CH3OC O COOH ⫹ NADH ⫹ H⫹

Exercises and Problems

21.24 Identify the enzyme needed in each of the following reactions

as an isomerase, a decarboxylase, a dehydrogenase, a protease, or a phosphatase. a. O O O B B B CH3OC OC OOH CH3OC OH ⫹ CO2 b. CHO CH2OH A A C PO HC O OH A A HOO CH HOOCH A A HC O OH HC O OH A A HO O CH HOOCH A A CH2OPO32⫺ CH2OPO32⫺ O c. O B B HO O C O CH2 O CH2 O C OOH O O B B HO O C O CHPCHO C OOH ⫹ 2H d.

O B H3NO CHOC ONH O CH O COO⫺⫹ H2O A A CH3 CH3 ⫹

⫹

2 H3N O CHO COO⫺ A CH3

731

Factors That Affect Enzyme Activity (Section 21.6) 21.37 Temperature affects enzymatic reaction rates in two ways. An

increase in temperature can accelerate the rate of a reaction or it can stop the reaction. Explain each of these effects. 21.38 Define the optimum temperature for an enzyme. 21.39 Explain why all enzymes do not possess the same optimum pH. 21.40 Why does an enzyme lose activity when the pH is drastically

changed from the optimum pH?

21.41 Draw a graph that shows the effect of increasing substrate

concentration on the rate of an enzyme-catalyzed reaction (at constant temperature, pH, and enzyme concentration). 21.42 Draw a graph that shows the effect of increasing enzyme concentration on the rate of an enzyme-catalyzed reaction (at constant temperature, pH, and substrate concentration). 21.43 In an enzyme-catalyzed reaction, all of the enzyme active sites

are saturated by substrate molecules at a certain substrate concentration. What happens to the rate of the reaction when the substrate concentration is doubled? 21.44 What is an enzyme turnover number? 21.45 What is an extremozyme? 21.46 Why are extremozymes of commercial importance?

Enzyme Inhibition (Section 21.7) 21.47 In competitive inhibition, can both the inhibitor and the

Models of Enzyme Action (Section 21.4) 21.25 What is an enzyme active site? 21.26 What is an enzyme–substrate complex?

substrate bind to an enzyme at the same time? Explain your answer. 21.48 Compare the sites where competitive and noncompetitive inhibitors bind to enzymes.

21.27 How does the lock-and-key model of enzyme action explain the

21.49 Indicate whether each of the following statements describes a

highly specific way some enzymes select a substrate? 21.28 How does the induced-fit model of enzyme action explain the broad specificities of some enzymes?

21.29 What types of forces hold a substrate at an enzyme active site? 21.30 The forces that hold a substrate at an enzyme active site are not

covalent bonds. Explain why not.

Enzyme Specificity (Section 21.5) 21.31 Define the following terms dealing with enzyme specificity. a. Absolute specificity b. Linkage specificity 21.32 Define the following terms dealing with enzyme specificity. a. Group specificity b. Stereochemical specificity 21.33 Which type(s) of enzyme specificity are best accounted for by

the lock-and-key model of enzyme action?

21.34 Which type(s) of enzyme specificity are best accounted for by

the induced-fit model of enzyme action?

21.35 Which enzyme in each of the following pairs would be more

limited in its catalytic scope? a. An enzyme that exhibits absolute specificity or an enzyme that exhibits group specificity b. An enzyme that exhibits stereochemical specificity or an enzyme that exhibits linkage specificity 21.36 Which enzyme in each of the following pairs would be more limited in its catalytic scope? a. An enzyme that exhibits linkage specificity or an enzyme that exhibits absolute specificity b. An enzyme that exhibits group specificity or an enzyme that exhibits stereochemical specificity

reversible competitive inhibitor, a reversible noncompetitive inhibitor, or an irreversible inhibitor. More than one answer may apply. a. Both inhibitor and substrate bind at the active site on a random basis. b. The inhibitor effect cannot be reversed by the addition of more substrate. c. Inhibitor structure does not have to resemble substrate structure. d. The inhibitor can bind to the enzyme at the same time as substrate. 21.50 Indicate whether each of the following statements describes a reversible competitive inhibitor, a reversible noncompetitive inhibitor, or an irreversible inhibitor. More than one answer may apply. a. It bonds covalently to the enzyme active site. b. The inhibitor effect can be reversed by the addition of more substrate. c. Inhibitor structure must be somewhat similar to that of substrate. d. The inhibitor cannot bind to the enzyme at the same time as substrate. Regulation of Enzyme Activity (Section 21.8) 21.51 What is an allosteric enzyme? 21.52 What is a regulator molecule? 21.53 What is feedback control? 21.54 What is the difference between positive and negative feedback

to an allosteric enzyme?

732

Chapter 21 Enzymes and Vitamins

21.55

21.80 Indicate whether each of the vitamins in Problem 21.78

Why are proteolytic enzymes always produced in an inactive form? 21.58 What is the mechanism by which most zymogens are activated?

Water-Soluble Vitamins (Section 21.12) 21.81 Describe the two most completely characterized roles of vitamin C in the body. 21.82 Structurally, how do the oxidized and reduced forms of vitamin C differ?

What is the general relationship between zymogens and proteolytic enzymes? 21.56 What, if any, is the difference in meaning between the terms zymogen and proenzyme? 21.57

What is covalent modification? 21.60 What are the two most commonly encountered covalent modification processes? 21.59

21.61 21.62

What is the most common source for the phosphate group involved in phosphorylation? Is the phosphorylated version of an enzyme the “turned-on” form or the “turned-off” form of the enzyme?

What is the general name for enzymes that effect the phosphorylation of another enzyme? 21.64 What is the general name for enzymes that effect the dephosphorylation of another enzyme? 21.63

Antibiotics That Inhibit Enzyme Activity (Section 21.9) 21.65 By what mechanism do sulfa drugs kill bacteria? 21.66 By what mechanism do penicillins kill bacteria? Why is penicillin toxic to bacteria but not to higher organisms? 21.68 What amino acid in transpeptidase forms a covalent bond to penicillin? 21.67

21.69 21.70

What situation has made Cipro a prominent antibiotic? Describe the structure of Cipro in terms of common and “unusual” functional groups present.

Medical Uses of Enzymes (Section 21.10) What does the acronym TPA stand for and how is TPA used in diagnostic medicine? 21.72 What does the acronym BUN test stand for and how is this test used in clinical laboratory analysis? 21.71

21.73 What are isoenzymes? 21.74

How are isoenzymes used in the diagnosis of a heart attack?

General Characteristics of Vitamins (Section 21.11) 21.75 What is a vitamin? 21.76 List a way in which vitamins differ from carbohydrates, fats, and proteins (the major classes of food). Indicate whether each of the following is a fat-soluble or a water-soluble vitamin. a. Vitamin K b. Vitamin B12 c. Vitamin C d. Thiamin 21.78 Indicate whether each of the following is a fat-soluble or a water-soluble vitamin. a. Vitamin A b. Vitamin B6 c. Vitamin E d. Riboflavin 21.77

21.79 Indicate whether each of the vitamins in Problem 21.77

would be likely or unlikely to be toxic when consumed in excess.

would be likely or unlikely to be toxic when consumed in excess.

What is the dominant function within the human body of the B vitamins as a group? 21.84 With the help of Table 21.7, identify the B vitamin or vitamins to which each of the following characterizations applies. a. Is part of the coenzymes NAD and NADP b. Is part of coenzyme A c. Is part of THF d. Is part of TPP 21.83

With the help of Table 21.6, indicate whether each of the following B vitamins exists in more than one structural form. a. Folate b. Niacin c. Vitamin B6 d. Biotin 21.86 With the help of Table 21.6, identify the B vitamin or vitamins to which each of the following characterizations applies. a. Contains a heterocyclic nitrogen ring system b. Has the most complex structure c. Contains a metal atom as part of its structure d. Contains sulfur as part of its structure 21.85

Fat-Soluble Vitamins (Section 21.13) Describe the structural differences among the three retinoid forms of vitamin A. 21.88 What is the relationship between the plant pigment betacarotene and vitamin A? 21.87

What is cell differentiation and how does vitamin A participate in this process? 21.90 List four major functions for vitamin A in the human body. 21.89

21.91 21.92

How do vitamin D2 and vitamin D3 differ in structure? In terms of source, how do vitamin D2 and vitamin D3 differ?

21.93 What is the principal function of vitamin D in the human 21.94

body? Why is vitamin D often called the sunshine vitamin?

Which form of tocopherol (vitamin E) exhibits the greatest biochemical activity? 21.96 How do the various forms of tocopherol differ in structure? 21.95

21.97 What is the principal function of vitamin E in the human 21.98

body? Why is vitamin E often given to premature infants that are on oxygen therapy?

21.99

How do vitamin K1 and vitamin K2 differ in structure?

21.100 In terms of source, how do vitamin K1 and vitamin K2

differ?

21.101 How are menaquinones, phylloquinones, and vitamin K

related?

21.102 What is the principal function of vitamin K in the human

body?

Multiple-Choice Practice Test

733

A DD D ITIO NA L P R O BL L EMS 21.103 Explain the difference, if any, between the following types of

enzymes. a. Apoenzyme and proenzyme b. Simple enzyme and allosteric enzyme c. Coenzyme and isoenzyme d. Conjugated enzyme and holoenzyme 21.104 Identify the functional groups present in a molecule of each of the following vitamins. a. Vitamin C b. Vitamin A (retinol) c. Vitamin D d. Vitamin K 21.105 Indicate whether each of the following vitamins functions as a coenzyme. a. Vitamin C b. Vitamin A c. Riboflavin d. Biotin 21.106 Which vitamin has each of the following functions? a. Water-soluble antioxidant b. Fat-soluble antioxidant c. Involved in the process of calcium deposition in bone d. Involved in the blood-clotting process

21.107 Which vitamin has each of the following functions?

a. Involved in cell differentiation b. Involved in vision c. Involved in collagen formation d. Involved in prostaglandin formation 21.108 What general kinds of reactions do the following types of enzymes catalyze? a. Lyases b. Ligases c. Hydrolases d. Transferases 21.109 Alcohol dehydrogenase catalyzes the conversion of ethanol to acetaldehyde. This enzyme, in its active state, consists of a protein molecule and a zinc ion. On the basis of this information, identify the following for this chemical system. a. Substrate b. Cofactor c. Apoenzyme d. Holoenzyme 21.110 Each of the following is an abbreviation for an enzyme used in the diagnosis and/or treatment of heart attacks. What does each abbreviation stand for? a. TPA b. LDH c. CPK d. AST

multiple-Choice Practice Test 21.111 Which are the two most common endings for the name of an

21.112

21.113

21.114

21.115

enzyme? a. -ase and -ose b. -ase and -in c. -in and -ogen d. -in and -ine Which of the following pairings of enzyme type and enzyme function is incorrect? a. Kinase and transfer of a phosphate group between substrates b. Mutase and introduction of a double bond within a molecule c. Protease and hydrolysis of amide linkages in proteins d. Decarboxylase and removal of CO2 from a substrate Which of the following is true for a conjugated enzyme? a. It contains only protein. b. It does not contain protein. c. It has a nonprotein part. d. It always contains a metal ion. Which of the following statements concerning cofactors is incorrect? a. All conjugated enzymes contain cofactors. b. Some cofactors are metal ions. c. A cofactor is the nonprotein portion of an enzyme. d. Vitamins cannot be cofactors. What happens to substrate molecules at an enzyme active site? a. They always react with O2. b. They become covalently bonded to the enzyme. c. They become catalysts. d. They undergo change to a desired product.

21.116 Which of the following statements about a reversible non-

21.117

21.118

21.119

21.120

competitive inhibitor is correct? a. It prevents substrate from occupying the enzyme active site. b. It must resemble the substrate in general shape. c. It and the substrate can simultaneously occupy the active site. d. It binds to the enzyme at a location other than the active site. What is the shape of a plot of enzyme activity (y-axis) versus temperature (x-axis) with other variables constant? a. Straight line with an upward slope b. Line with an upward slope and a long flat top c. Line with an upward slope followed by a downward slope d. Straight horizontal line Which of the following statements concerning the B vitamins is correct? a. Structurally, they are all very similar. b. All except two of them are water soluble. c. In chemically modified form they often serve as cofactors in enzymes. d. Fruits, in general, are very good sources of these vitamins. Cholesterol is a precursor for which of the following vitamins? a. Vitamin A b. Vitamin C c. Vitamin D d. Vitamin E Beta-carotene is a precursor for which of the following vitamins? a. Vitamin A b. Vitamin D c. Vitamin E d. Vitamin K

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22

Nucleic Acids Chapter Outline 22.1

Types of Nucleic Acids 734

22.2 Nucleotides: Building Blocks of Nucleic Acids 735 22.3 Primary Nucleic Acid Structure 738

CHEMISTRY AT A GLANCE: Nucleic Acid Structure 741 22.4 The DNA Double Helix 741 22.5 Replication of DNA Molecules 745 22.6 Overview of Protein Synthesis 747 22.7

Ribonucleic Acids 747

CHEMISTRY AT A GLANCE: DNA Replication 748 22.8 Transcription: RNA Synthesis 749 22.9

The Genetic Code 753

22.10 Anticodons and tRNA Molecules 756 22.11 Translation: Protein Synthesis 758 22.12 Mutations 763

CHEMISTRY AT A GLANCE: Protein Synthesis: Transcription and Translation 764 22.13 Nucleic Acids and Viruses 763 22.14 Recombinant DNA and Genetic Engineering 765 22.15 The Polymerase Chain Reaction 768 22.16 DNA Sequencing 769

CHEMICAL CONNECTIONS Use of Synthetic Nucleic Acid Bases in Medicine 738 Antibiotics That Inhibit Bacterial Protein Synthesis 761

It was not until 1944, 75 years after the discovery of nucleic acids, that scientists obtained the first evidence that these molecules are responsible for the storage and transfer of genetic information.

Human egg and sperm.

A

most remarkable property of living cells is their ability to produce exact replicas of themselves. Furthermore, cells contain all the instructions needed for making the complete organism of which they are a part. The molecules within a cell that are responsible for these amazing capabilities are nucleic acids. The Swiss physiologist Friedrich Miescher (1844–1895) discovered nucleic acids in 1869 while studying the nuclei of white blood cells. The fact that they were initially found in cell nuclei and are acidic accounts for the name nucleic acid. Although we now know that nucleic acids are found throughout a cell, not just in the nucleus, the name is still used for such materials.

22.1 TYPES OF NUCLEIC ACIDS Two types of nucleic acids are found within cells of higher organisms: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nearly all the DNA is found within the cell nucleus. Its primary function is the storage and transfer of genetic information. This information is used (indirectly) to control many functions of a living cell. In addition, DNA is passed from existing cells to new cells during cell division. RNA occurs in all parts of a cell. It functions primarily in synthesis of proteins, the molecules that carry out essential cellular functions. The structural distinctions between DNA and RNA molecules are considered in Section 22.3. All nucleic acid molecules are polymers. A nucleic acid is a polymer in which the monomer units are nucleotides. Thus the starting point for a discussion of nucleic acids is an understanding of the structures and chemical properties of nucleotides.

734 Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

22.2 Nucleotides: Building Blocks of Nucleic Acids

735

22.2 NUCLEOTIDES: BUILDING BLOCKS OF NUCLEIC ACIDS Proteins are polypeptides, many carbohydrates are polysaccharides, and nucleic acids are polynucleotides.

A nucleotide is a three-subunit molecule in which a pentose sugar is bonded to both a phosphate group and a nitrogen-containing heterocyclic base. With a three-subunit structure, nucleotides are more complex monomers than the monosaccharides of polysaccharides (Section 18.8) and the amino acids of proteins (Section 20.2). A block structural diagram for a nucleotide is Base Phosphate

Sugar

Pentose Sugars The sugar unit of a nucleotide is either the pentose ribose or the pentose 2⬘-deoxyribose. The systems for numbering the atoms in the pentose and nitrogen-containing base subunits of a nucleotide are important and will be used extensively in later sections of this chapter. The convention is that 1. Pentose ring atoms are designated with primed numbers. 2. Nitrogen-containing base ring atoms are designated with unprimed numbers.

5⬘

O

HOCH2

5⬘

4⬘

1⬘

2⬘

OH

OH

OH

4⬘

1⬘ 3⬘

O

HOCH2

OH

␤ -D-Ribose

3⬘

2⬘

OH

H

␤ -D-2⬘-Deoxyribose

Structurally, the only difference between these two sugars occurs at carbon 2⬘. The 9OH group present on this carbon in ribose becomes a 9H atom in 2⬘-deoxyribose. (The prefix deoxy- means “without oxygen.”) RNA and DNA differ in the identity of the sugar unit in their nucleotides. In RNA the sugar unit is ribose9hence the R in RNA. In DNA the sugar unit is 2⬘-deoxyribose9hence the D in DNA.

Nitrogen-Containing Heterocyclic Bases Five nitrogen-containing heterocyclic bases are nucleotide components. Three of them are derivatives of pyrimidine (Section 17.9), a monocyclic base with a six-membered ring, and two are derivatives of purine (Section 17.9), a bicyclic base with fused five- and sixmembered rings. 4

N

5

B

F

6

A pyrimidine derivative that we have encountered previously is the B vitamin thiamine (see Section 21.12).

N1

2

7

N

3 8

9

N A H

Pyrimidine

B

F

Caffeine, the most widely used nonprescription central nervous system stimulant, is the 1,3,7trimethyl-2,6-dioxo derivative of purine (Section 17.9).

5 4

6

N N

1

2

3

Purine

Both of these heterocyclic compounds are bases because they contain amine functional groups (secondary or tertiary), and amine functional groups exhibit basic behavior (proton acceptors; Section 17.6). The three pyrimidine derivatives found in nucleotides are thymine (T), cytosine (C), and uracil (U). O CH3

5

4

H E N

NH2

O

4

4

2

N A H Thymine (T)

N

2

2

O

N A H

H E N

O

Cytosine (C)

N A H

O

Uracil (U)

Thymine is the 5-methyl-2,4-dioxo derivative, cytosine the 4-amino-2-oxo derivative, and uracil the 2,4-dioxo derivative of pyrimidine.

736

Chapter 22 Nucleic Acids

The two purine derivatives found in nucleotides are adenine (A) and guanine (G). NH2 N

6

O

N

N

6

N f H

N

H E N 2

N f H

N

Adenine (A)

Figure 22.1 Space-filling model of the molecule adenine, a nitrogencontaining heterocyclic base present in both DNA and RNA.

NH2

Guanine (G)

Adenine is the 6-amino derivative of purine, and guanine is the 2-amino-6-oxo purine derivative. A space-filling model for adenine is shown in Figure 22.1. Adenine, guanine, and cytosine are found in both DNA and RNA. Uracil is found only in RNA, and thymine usually occurs only in DNA. Figure 22.2 summarizes the occurrences of nitrogen-containing heterocyclic bases in nucleic acids.

Phosphate Phosphate, the third component of a nucleotide, is derived from phosphoric acid (H3PO4). Under cellular pH conditions, the phosphoric acid loses two of its hydrogen atoms to give a hydrogen phosphate ion (HPO42). O A O P P O OH  2H  A O

OH A O P P O OH A OH Phosphoric acid

Hydrogen phosphate ion

Nucleotide Formation The formation of a nucleotide from sugar, base, and phosphate can be visualized as occurring in the following manner: Base

O N

7 89

O A OP P OOH A O

N A H

H2O 5

HOOOCH2

O

1 3

OH Phosphate

OH

4 2

H E N NH2 N H2O

O E N

N

O A 5 OP P OOO CH2 A 4 O

7 8 9

O

N A

N

H

NH2

1 3

2

OH

 2H2O

OH

OH

Sugar

Nucleotide

Important characteristics of this combining of three molecules into one molecule (the nucleotide) are that 1. Condensation, with formation of a water molecule, occurs at two locations: between sugar and base and between sugar and phosphate. 2. The base is always attached at the C-1 position of the sugar. For purine bases, attachment is through N-9; for pyrimidine bases, N-1 is involved. The C-1 carbon atom of the ribose unit is always in a b configuration (Section 18.10), and the bond connecting the sugar and base is a b-N-glycosidic linkage (Section 18.13). 3. The phosphate group is attached to the sugar at the C-5 position through a phosphate– ester linkage.

737

22.2 Nucleotides: Building Blocks of Nucleic Acids

Figure 22.2 Two purine bases and three pyrimidine bases are found in the nucleotides present in nucleic acids.

N N

N

N N

N

H Purine

In both DNA and RNA NH2 O H N N N N

H

CH3 N Pyrimidine

pure Ag purine A and G

NH2

Guanine G NH2

N

N

N

H Adenine A

O To remember which two of the five nucleotide bases are the purine derivatives (fused rings), use the phrase “pure silver” and the chemical symbol for silver, which is Ag.

N

N

H

O

N

O

N

H Thymine T

H

N O

N

H Cytosine C In DNA

O

H Uracil U In RNA

There are four possible RNA nucleotides, differing in the base present (A, C, G, or U), and four possible DNA nucleotides, differing in the base present (A, C, G, or T).

Nucleotide Nomenclature The common names and abbreviations for the eight nucleotides of DNA and RNA molecules are given in Table 22.1. It is important to be familiar with them because they are frequently encountered in biochemistry. We can make several generalizations about the nomenclature given in Table 22.1. 1. All of the names end in 5-monophosphate, which signifies the presence of a phosphate group attached to the 5 carbon atom of ribose or deoxyribose. (In Chapter 23 we will encounter nucleotides that contain two or three phosphate groups—diphosphates and triphosphates.) 2. Preceding the monophosphate ending is the name of the base present in a modified form. The suffix -osine is used with purine bases, the suffix -idine with pyrimidine bases. 3. The prefix deoxy- at the start of the name signifies that the sugar present is deoxyribose. When no prefix is present, the sugar is ribose.

TABLE 22.1 The Names of the Eight Nucleotides Found in DNA and RNA

Base

Sugar

Nucleotide Name

Nucleotide Abbreviation

deoxyribose deoxyribose deoxyribose deoxyribose

deoxyadenosine 5-monophosphate deoxyguanosine 5-monophosphate deoxycytidine 5-monophosphate deoxythymidine 5-monophosphate

dAMP dGMP dCMP dTMP

ribose ribose ribose ribose

adenosine 5-monophosphate guanosine 5-monophosphate cytidine 5-monophosphate uridine 5-monophosphate

AMP GMP CMP UMP

DNA Nucleotides

adenine guanine cytosine thymine RNA Nucleotides

adenine guanine cytosine uracil

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c

HEMICAL

onnections

Use of Synthetic Nucleic Acid Bases in Medicine

Many hundreds of modified nucleic acid bases have been prepared in laboratories and their effects on nucleic acid synthesis investigated. Several of them are now in clinical use as drugs for controlling, at the cellular level, cancers and other related disorders. The theory behind the use of these modified bases involves their masquerading as legitimate nucleic acid building blocks. The enzymes associated with the DNA replication process (Section 22.5) incorporate the modified bases into growing nucleic acid chains. The presence of these “pseudonucleotides” in the chain stops further growth of the chain, thus interfering with nucleic acid synthesis. Examples of drugs now in use include 5-fluorouracil, which is employed against a variety of cancers, especially those of the breast and digestive tract, and 6-mercaptopurine, which is used in the treatment of leukemia. O

O

F NH N

H3C

H 5-Fluorouracil (a modified thymine)

NH2 N

N

and N

N H

N

N

N H

N

6-Mercaptopurine (a modified adenine)

Adenine

The rapidly dividing cells that are characteristic of cancer require large quantities of DNA. Anticancer drugs based on modified nucleic acid bases block DNA synthesis and therefore block the increase in the number of cancer cells. Cancer cells are generally affected to a greater extent than normal cells because of this rapid growth. Eventually, the normal cells are affected to such a degree that use of the drugs must be discontinued. 5-Fluorouracil inhibits the formation of thymine-containing nucleotides required for DNA synthesis. 6-Mercaptopurine, which substitutes for adenine, inhibits the synthesis of nucleotides that incorporate adenine and guanine.

NH

and

O

SH

N

O

H Thymine

4. The abbreviations in Table 22.1 for the nucleotides come from the one-letter symbols for the bases (A, C, G, T, and U), the use of MP for monophosphate, and a lower-case d at the start of the abbreviation whenever deoxyribose is the sugar. The use of synthetic nucleic acid bases in medicine is considered in the Chemical Connections feature on this page.

22.3 PRIMARY NUCLEIC ACID STRUCTURE

Nucleotides are related to nucleic acids in the same way that amino acids are related to proteins.

Figure 22.3 The general structure of a nucleic acid in terms of nucleotide subunits.

Nucleic acids are polymers in which the repeating units, the monomers, are nucleotides (Section 22.2). The nucleotide units within a nucleic acid molecule are linked to each other through sugar–phosphate bonds. The resulting molecular structure (Figure 22.3) involves a chain of alternating sugar and phosphate groups with a base group protruding from the chain at regular intervals. We can now define, in terms of structure, the two major types of nucleic acids: ribonucleic acids and deoxyribonucleic acids (Section 22.1). A ribonucleic acid (RNA) is a nucleotide polymer in which each of the monomers contains ribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or uracil. Two changes to this definition generate the deoxyribonucleic acid definition; deoxyribose replaces ribose and thymine replaces uracil. A deoxyribonucleic acid (DNA) is a Base Phosphate

Sugar

Nucleotide

Base Phosphate

Sugar

Nucleotide

Base Phosphate

Sugar

Nucleotide

22.3 Primary Nucleic Acid Structure

Figure 22.4 (a) The generalized backbone structure of a nucleic acid. (b) The specific backbone structure for a deoxyribonucleic acid (DNA). (c) The specific backbone structure for a ribonucleic acid (RNA).

Phosphate

Phosphate

Phosphate

Sugar

Deoxyribose

Ribose

Phosphate

Phosphate

Phosphate

Sugar

Deoxyribose

Ribose

Phosphate

Phosphate

Phosphate

Sugar

Deoxyribose

Ribose

(a) Nucleic Acid

The backbone of a nucleic acid structure is always an alternating sequence of phosphate and sugar groups. The sugar is ribose in RNA and deoxyribose in DNA.

B

B

F

F

Just as the order of amino acid side chains determines the primary structure of a protein (Section 20.9), the order of nucleotide bases determines the primary structure of a nucleic acid.

For both nucleic acids and proteins, a distinction is made between the two ends of the polymer chain. For nucleic acids there is a 5 end and a 3 end; for proteins there is an N-terminal end and a C-terminal end (Section 20.6).

(b) DNA

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(c) RNA

nucleotide polymer in which each of the monomers contains deoxyribose, a phosphate group, and one of the heterocyclic bases adenine, cytosine, guanine, or thymine. The alternating sugar–phosphate chain in a nucleic acid structure is often called the nucleic acid backbone. This backbone is constant throughout the entire nucleic acid structure. For DNA molecules, the backbone consists of alternating phosphate and deoxyribose sugar units; for RNA molecules, the backbone consists of alternating phosphate and ribose sugar units. Figure 22.4 contrasts the generalized backbone structure for a nucleic acid with the specific backbone structures of DNAs and RNAs. The variable portion of nucleic acid structure is the sequence of bases attached to the sugar units of the backbone. The sequence of these base side chains distinguishes various DNAs from each other and various RNAs from each other. Only four types of bases are found in any given nucleic acid structure. This situation is much simpler than that for proteins, where 20 side-chain entities (amino acids) are available (Section 20.2). In both RNA and DNA, adenine, guanine, and cytosine are encountered as side-chain components; thymine is found mainly in DNA, and uracil is found only in RNA (Figure 22.2). Primary nucleic acid structure is the sequence in which nucleotides are linked together in a nucleic acid. Because the sugar–phosphate backbone of a given nucleic acid does not vary, the primary structure of the nucleic acid depends only on the sequence of bases present. Further information about nucleic acid structure can be obtained by considering the detailed four-nucleotide segment of a DNA molecule shown in Figure 22.5. The following list describes some important points about nucleic acid structure that are illustrated in Figure 22.5. 1. Each nonterminal phosphate group of the sugar–phosphate backbone is bonded to two sugar molecules through a 3,5-phosphodiester linkage. There is a phosphoester bond to the 5 carbon of one sugar unit and a phosphoester bond to the 3 carbon of the other sugar. 2. A nucleotide chain has directionality. One end of the nucleotide chain, the 5 end, normally carries a free phosphate group attached to the 5 carbon atom. The other end of the nucleotide chain, the 3 end, normally has a free hydroxyl group attached to the 3 carbon atom. By convention, the sequence of bases of a nucleic acid strand is read from the 5 end to the 3 end. 3. Each nonterminal phosphate group in the backbone of a nucleic acid carries a 1 charge. The parent phosphoric acid molecule from which the phosphate was derived originally had three 9OH groups (Section 22.2). Two of these become involved in the 3,5-phosphodiester linkage. The remaining 9OH group is free to exhibit acidic behavior9that is, to produce a H ion. O B , OO P OO, A OH

O B , OO P OO,  H A O

This behavior by the many phosphate groups in a nucleic acid backbone gives nucleic acids their acidic properties.

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Chapter 22 Nucleic Acids

Figure 22.5 A four-nucleotide-long

Thymine

segment of DNA. (The choice of bases was arbitrary.)

O CH3 O– O

P

O

O–

Guanine

2'

O

H

O O

O

N

5' CH2 O 4' 3'

3',5'-Phosphodiester linkage

H

N

5' end

P

O

O–

N

N

N

5' CH2 O 4'

N

NH2

Cytosine

2'

3'

H

NH2

H

N O

3',5'-Phosphodiester linkage

O

P O

O –

NH2

H

O O

Adenine

2'

3'

3',5'-Phosphodiester linkage

O

N

5' CH2 O 4'

P O

O –

N

N

N

5' CH2 O 4'

N

2'

3'

H OH

3' end

Three parallels between primary nucleic acid structure and primary protein structure (Section 20.9) are worth noting. 1. DNAs, RNAs, and proteins all have backbones that do not vary in structure (see Figure 22.6). 2. The sequence of attachments to the backbones (nitrogen bases in nucleic acids and amino acid R groups in proteins) distinguishes one DNA from another, one RNA from another, and one protein from another (see Figure 22.6). 3. Both nucleic acid polymer chains and protein polymer chains have directionality; for nucleic acids there is a 5 end and a 3 end, and for proteins there is an N-terminal end and a C-terminal end. The Chemistry at a Glance feature on page 741 summarizes important concepts relative to the makeup of the nucleotide building blocks (monomers) present in polymeric DNA and RNA molecules. Figure 22.6 A comparison of the general primary structures of nucleic acids and proteins.

5' end A nucleic acid

Different bases Base1

Phosphate

Sugar

Base2 Phosphate

NH

R1

O

CH

C

Sugar

Base3 Phosphate

Different R Groups

N-terminal end A protein

3' end

NH

R2

O

CH

C

NH

Sugar

C-terminal end R3

O

CH

C

NH

R4

O

CH

C

22.4 The DNA Double Helix

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Nucleic Acid Structure NUCLEIC ACID STRUCTURE Base Phosphate

Base

Sugar

Phosphate

Nucleotide

Base

Sugar

Phosphate

Nucleotide

Sugar

Nucleotide

DEOXYRIBONUCLEIC ACID (DNA)

RIBONUCLEIC ACID (RNA)

Nucleotide Components

Nucleotide Components

Sugar

Phosphate

HOCH2 O

O

P O

OH H ␤-D-2'-Deoxyribose

Phosphate

HOCH2 O

O– OH

Sugar

O–

OH

O

OH

O

OH OH

Hydrogen phosphate ion

␤-D-Ribose

N N

Bases O

N

CH3

O

NH2

H

N

N

H O

N

N

H

H

N

N

N

O

N

N

H

H

Adenine (A)

Thymine (T)

Adenine (A)

Uracil (U)

O

NH2

O

NH2

N N

H

N N

NH2

H

N

N N

O

H Guanine (G)

OH –

Hydrogen phosphate ion

Bases NH2

P

–

N

H

N N

N N

NH2

H

Cytosine (C)

POSSIBLE NUCLEOTIDES dAMP dGMP dCMP dTMP

O

H Guanine (G)

Cytosine (C)

POSSIBLE NUCLEOTIDES AMP

GMP

CMP

UMP

22.4 THE DNA DOUBLE HELIX Like proteins, nucleic acids have secondary, or three-dimensional, structure as well as primary structure. The secondary structures of DNAs and RNAs differ, and we will discuss them separately. The amounts of the bases A, T, G, and C present in DNA molecules were the key to determination of the general three-dimensional structure of DNA molecules. Base composition data for DNA molecules from many different organisms revealed a definite pattern of

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Chapter 22 Nucleic Acids

Figure 22.7 Three views of the DNA double helix. (a) A schematic drawing that emphasizes the hydrogen bonding between bases on the two chains. (b) A space-filling model in which one DNA strand is blue and the other strand is orange. The bases are shown in lighter shades of blue and orange. (c) A top view of the double helix.

Hydrogen bonds 5' 3' T C

G C A

G

A

T G

C T

A T

A

T T C G

Sugar–phosphate backbone

A A

G

C

A

T A

T

5'

3' Base pair (a)

(b)

(c)

base occurrence. The amounts of A and T were always equal, and the amounts of C and G were always equal, as were the amounts of total purines and total pyrimidines. The relative amounts of these base pairs in DNA vary depending on the life form from which the DNA is obtained. (Each animal or plant has a unique base composition.) However, the relationships %A  %T

B

F

The a-helix secondary structure of proteins (Section 20.10) involves one polypeptide chain; the double-helix secondary structure of DNA involves two polynucleotide chains. In the ahelix of proteins, the R groups are on the outside of the helix; in the double helix of DNA, the bases are on the inside of the double helix.

and

%C  %G

always hold true. For example, human DNA contains 30% adenine, 30% thymine, 20% guanine, and 20% cytosine. In 1953, an explanation for the base composition patterns associated with DNA molecules was proposed by the American microbiologist James Watson and the English biophysicist Francis Crick. Their model, which has now been validated in numerous ways, involves a double-helix structure that accounts for the equality of bases present, as well as for other known DNA structural data. The DNA double helix involves two polynucleotide strands coiled around each other in a manner somewhat like a spiral staircase. The sugar–phosphate backbones of the two polynucleotide strands can be thought of as being the outside banisters of the spiral staircase (see Figure 22.7). The bases (side chains) of each backbone extend inward toward the bases of the other strand. The two strands are connected by hydrogen bonds (Section 7.13) between their bases. Additionally, the two strands of the double helix are antiparallel—that is, they run in opposite directions. One strand runs in the 5-to-3 direction, and the other is oriented in the 3-to-5 direction.

Base Pairing A physical restriction, the size of the interior of the DNA double helix, limits the base pairs that can hydrogen-bond to one another. Only pairs involving one small base (a

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

22.4 The DNA Double Helix

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Figure 22.8 Hydrogen-bonding possibilities are more favorable when A–T and G–C base pairing occurs than when A–C and G–T base pairing occurs. (a) Two and three hydrogen bonds can form, respectively, between A–T and G–C base pairs. These combinations are present in DNA molecules. (b) Only one hydrogen bond can form between G–T and A–C base pairs. These combinations are not present in DNA molecules.

A mnemonic device for recalling base-pairing combinations in DNA involves listing the base abbreviations in alphabetical order. Then the first and last bases pair, and so do the middle two bases. DNA:

ACGT

Another way to remember these base-pairing combinations is to note that AT spells a word and that C and G look very much alike.

The antiparallel nature of the two polynucleotide chains in the DNA double helix means that there is a 5 end and a 3 end at both ends of the double helix.

The two strands of DNA in a double helix are complementary. This means that if you know the order of bases in one strand, you can predict the order of bases in the other strand.

C

G

A

T

Thymine–Adenine Base Pairing (two hydrogen bonds form)

Cytosine–Guanine Base Pairing (three hydrogen bonds form) (a)

T

G C

Thymine–Guanine Base Pairing (only one hydrogen bond forms)

A

Cytosine–Adenine Base Pairing (only one hydrogen bond forms) (b)

Carbon

Oxygen

Lone pair

Hydrogen bond

Nitrogen

Hydrogen

Attachment to backbone

pyrimidine) and one large base (a purine) correctly “fit” within the helix interior. There is not enough room for two large purine bases to fit opposite each other (they overlap), and two small pyrimidine bases are too far apart to hydrogen-bond to one another effectively. Of the four possible purine–pyrimidine combinations (A–T, A–C, G–T, and G–C), hydrogen-bonding possibilities are most favorable for the A–T and G–C pairings, and these two combinations are the only two that normally occur in DNA. Figure 22.8 shows the specific hydrogen-bonding interactions for the four possible purine–pyrimidine basepairing combinations. The pairing of A with T and that of G with C are said to be complementary. A and T are complementary bases, as are G and C. Complementary bases are pairs of bases in a nucleic acid structure that can hydrogen-bond to each other. The fact that complementary base pairing occurs in DNA molecules explains, very simply, why the amounts of the bases A and T present are always equal, as are the amounts of G and C. The two strands of DNA in a double helix are not identical—they are complementary. Complementary DNA strands are strands of DNA in a double helix with base pairing such that each base is located opposite its complementary base. Wherever G occurs in one strand, there is a C in the other strand; wherever T occurs in one strand, there is an A in the other strand. An important ramification of this complementary relationship is that knowing the base sequence of one strand of DNA enables us to predict the base sequence of the complementary strand. In specifying the base sequence of a segment of a strand of DNA (or RNA), we list the bases in sequential order (using their one-letter abbreviations) in the direction from the 5 end to the 3 end of the segment. 5 A–A–G–C–T–A–G–C–T–T–A–C–T 3

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Chapter 22 Nucleic Acids

EXAMPLE 22.1 Predicting Base Sequence in a Complementary DNA Strand

Predict the sequence of bases in the DNA strand that is complementary to the single DNA strand shown. 5 C–G–A–A–T–C–C–T–A 3 Solution

Because only A forms a complementary base pair with T, and only G with C, the complementary strand is as follows: Given:

5 C–G–A–A–T–C–C–T–A 3

Complementary strand: 3 G–C–T–T–A–G–G–A–T 5 Note the reversal of the numbering of the ends of the complementary strand compared to the given strand. This is due to the antiparallel nature of the two strands in a DNA double helix.

Practice Exercise 22.1 Predict the sequence of bases in the DNA strand complementary to the single DNA strand shown. 5 A–A–T–G–C–A–G–C–T 3 Answer: 3 T–T–A–C–G–T–C–G–A 5

B

F

Hydrogen bonding is responsible for the secondary structure (double helix) of DNA. Hydrogen bonding is also responsible for secondary structure in proteins (Section 20.10).

Hydrogen bonding between base pairs is an important factor in stabilizing the DNA double helix structure. Although hydrogen bonds are relatively weak forces, each DNA molecule has so many base pairs that collectively these hydrogen bonds are a force of significant strength. In addition to hydrogen bonding, base-stacking interactions also contribute to DNA double-helix stabilization.

Base-Stacking Interactions The bases in a DNA double helix are positioned with the planes of their rings parallel (like a stack of coins). Stacking interactions involving a given base and the parallel bases directly above it and below it also contribute to the stabilization of the DNA double helix. These stacking interactions are as important in their stabilization effects as is the hydrogen bonding associated with base pairing—perhaps even more important. Purine and pyrimidine bases are hydrophobic in nature, so their stacking interactions are those associated with hydrophobic molecules—mainly London forces (Section 7.13). The concept of hydrophobic interactions has been encountered twice previously. Hydrophobic interactions involving the nonpolar tails of membrane lipids contribute to the structural stability of cell membranes (Section 19.10), and hydrophobic interactions involving nonpolar R groups of amino acids contribute to protein tertiary structure stability (Section 20.11).

Use of the Term “DNA Molecule” The term DNA molecule is actually a misnomer, even though general usage of the term is common in news reports, in textbooks, and even in the vocabulary of scientists. It is technically a misnomer for two reasons. 1. Cellular solutions have pH values such that the phosphate groups present in the DNA backbone structure are negatively charged. This means DNA is actually a multicharged ionic species rather than a neutral molecule. 2. The two strands of DNA in a double-helix structure are not held together by covalent bonds but rather by hydrogen bonds, which are noncovalent interactions. Thus, double-helix DNA is an entity that involves two intertwined ionic species rather than a single molecule.

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22.5 Replication of DNA Molecules

Despite these considerations, usage of the term DNA molecule is accepted by most scientists and it is used through the remainder of this textbook.

22.5 REPLICATION OF DNA MOLECULES DNA molecules are the carriers of genetic information within a cell; that is, they are the molecules of heredity. Each time a cell divides, an exact copy of the DNA of the parent cell is needed for the new daughter cell. The process by which new DNA molecules are generated is DNA replication. DNA replication is the biochemical process by which DNA molecules produce exact duplicates of themselves. The key concept in understanding DNA replication is the base pairing associated with the DNA double helix.

DNA Replication Overview To understand DNA replication, we must regard the two strands of the DNA double helix as a pair of templates, or patterns. During replication, the strands separate. Each can then act as a template for the synthesis of a new, complementary strand. The result is two daughter DNA molecules with base sequences identical to those of the parent double helix. Let us consider details of this replication. Under the influence of the enzyme DNA helicase, the DNA double helix unwinds, and the hydrogen bonds between complementary bases are broken. This unwinding process, as shown in Figure 22.9, is somewhat like opening a zipper. The bases of the separated strands are no longer connected by hydrogen bonds. They can pair with free individual nucleotides present in the cell’s nucleus. As shown in Figure 22.9, the base pairing always involves C pairing with G and A pairing with T. The pairing process occurs one nucleotide at a time. After a free nucleotide has formed hydrogen bonds with a base of the old strand (the template), the enzyme DNA polymerase verifies that the base pairing is correct and then catalyzes the formation of a new phosphodiester linkage between the nucleotide and the growing strand (represented by the darker blue ribbons in Figure 22.9). The DNA polymerase then slides down the strand to the next unpaired base of the template, and the same process is repeated. Each of the two daughter molecules of double-stranded DNA formed in the DNA replication process contains one strand from the original parent molecule and one newly formed strand.

The Replication Process in Finer Detail Though simple in principle, the DNA replication process has many intricacies. 1. The enzyme DNA polymerase can operate on a forming DNA daughter strand only in the 5-to-3 direction. Because the two strands of parent DNA run in opposite directions Figure 22.9 In DNA replication, the two strands of the DNA double helix unwind, the separated strands serving as templates for the formation of new DNA strands. Free nucleotides pair with the complementary bases on the separated strands of DNA. This process ultimately results in the complete replication of the DNA molecule.

3' Old G T A G

3' Old

T G

G

C

C

T C A G

5' Old

T

T

A

A

G

C

C

G

C

T

A

C G

T A

T T

T

A

A

T C

A

A

C G

G G

A

5' New

C G

3' New C A C T

T

T

A

A

T A

G C

G C

C G

A T

C G

5' Old

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Chapter 22 Nucleic Acids

Figure 22.10 Because the enzyme

3'

DNA polymerase can act only in the 5-to-3 direction, one strand (top) grows continuously in the direction of the unwinding, and the other strand grows in segments in the opposite direction. The segments in this latter chain are then connected by a different enzyme, DNA ligase.

Continuously 5' growing strand

3' 5'

Okazaki fragments Strand 3' growing in segments 5'

5'

Nick

(one is 5 to 3 and the other 3 to 5; Section 22.4), only one strand can grow continuously in the 5-to-3 direction. The other strand must be formed in short segments, called Okazaki fragments (after their discoverer, Reiji Okazaki), as the DNA unwinds (see Figure 22.10). The breaks or gaps in this daughter strand are called nicks. To complete the formation of this strand, the Okazaki fragments are connected by action of the enzyme DNA ligase. 2. The process of DNA unwinding does not have to begin at an end of the DNA molecule. It may occur at any location within the molecule. Indeed, studies show that unwinding usually occurs at several interior locations simultaneously and that DNA replication is bidirectional for these locations; that is, it proceeds in both directions from the unwinding sites. As shown in Figure 22.11, the result of this multiple-site replication process is formation of “bubbles” of newly synthesized DNA. The bubbles grow larger and eventually coalesce, giving rise to two complete daughter DNAs. Multiple-site replication enables large DNA molecules to be replicated rapidly.

Chromosomes Once the DNA within a cell has been replicated, it interacts with specific proteins in the cell called histones to form structural units that provide the most stable arrangement for the long DNA molecules. These histone–DNA complexes are called chromosomes. A chromosome is an individual DNA molecule bound to a group of proteins. Typically, a chromosome is about 15% by mass DNA and 85% by mass protein. Cells from different kinds of organisms have different numbers of chromosomes. A normal human has 46 chromosomes per cell, a mosquito 6, a frog 26, a dog 78, and a turkey 82. Chromosomes occur in matched (homologous) pairs. The 46 chromosomes of a human cell constitute 23 homologous pairs. One member of each homologous pair is Figure 22.11 DNA replication usually occurs at multiple sites within a molecule, and the replication is bidirectional from these sites.

Origins of replication Parent DNA Early stage in replication

Later stage in replication

Daughter DNAs

22.7 Ribonucleic Acids

Figure 22.12 Identical twins share identical physical characteristics because they received identical DNA from their parents.

Chromosomes are nucleoproteins. They are a combination of nucleic acid (DNA) and various proteins.

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derived from a chromosome inherited from the father, and the other is a copy of one of the chromosomes inherited from the mother. Homologous chromosomes have similar, but not identical, DNA base sequences; both code for the same traits but for different forms of the trait (for example, blue eyes versus brown eyes). Offspring are like their parents, but they are different as well; part of their DNA came from one parent and part from the other parent. Occasionally, identical twins are born (see Figure 22.12). Such twins have received identical DNA from their parents. The Chemistry at a Glance feature on page 748 summarizes the steps in DNA replication.

22.6 OVERVIEW OF PROTEIN SYNTHESIS We saw in the previous section how the replication of DNA makes it possible for a new cell to contain the same genetic information as its parent cell. We will now consider how the genetic information contained in a cell is expressed in cell operation. This brings us to the topic of protein synthesis. The synthesis of proteins (skin, hair, enzymes, hormones, and so on) is under the direction of DNA molecules. It is this role of DNA that establishes the similarities between parent and offspring that we regard as hereditary characteristics. We can divide the overall process of protein synthesis into two phases. The first phase is called transcription and the second translation. The following diagram summarizes the relationship between transcription and translation. Transcription

Translation

DNA 88888888n RNA 8888888n protein Before discussing the details of transcription and translation, we need to learn more about RNA molecules. They are involved in both transcription, as the end products, and translation, as the starting materials. We will be particularly concerned with differences between RNA and DNA and among various types of RNA molecules.

22.7 RIBONUCLEIC ACIDS B

Four major differences exist between RNA molecules and DNA molecules. F

The bases thymine (T) and uracil (U) have similar structures. Thymine is a methyluracil (Section 22.2). The hydrogen-bonding patterns (Figure 22.7) for the A–U base pair (RNA) and the A–T base pair (DNA) are identical.

1. The sugar unit in the backbone of RNA is ribose; it is deoxyribose in DNA. 2. The base thymine found in DNA is replaced by uracil in RNA (Figure 22.2). In RNA, uracil, instead of thymine, pairs with (forms hydrogen bonds with) adenine. 3. RNA is a single-stranded molecule; DNA is double-stranded (double helix). Thus RNA, unlike DNA, does not contain equal amounts of specific bases. 4. RNA molecules are much smaller than DNA molecules, ranging from 75 nucleotides to a few thousand nucleotides. We should note that the single-stranded nature of RNA does not prevent portions of an RNA molecule from folding back upon itself and forming double-helical regions. If the base sequences along two portions of an RNA strand are complementary, a structure with a hairpin loop results, as shown in Figure 22.13. The amount of double-helical structure present in an RNA varies with RNA type, but a value of 50% is not atypical.

Types of RNA Molecules Heterogeneous nuclear RNA (hnRNA) also goes by the name primary transcript RNA (ptRNA).

RNA molecules found in human cells are categorized into five major types, distinguished by their function. These five RNA types are heterogeneous nuclear RNA (hnRNA), messenger RNA (mRNA), small nuclear RNA (snRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).

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Chapter 22 Nucleic Acids

DNA Replication

STEP 2 Free nucleotides pair with their complementary base on the template strands by means of hydrogen bonds.

G

A

C

STEP 3 DNA polymerase joins the newly attached nucleotides to create one continuous strand in the 5'-to-3' direction.

T

STEP 1 The enzyme DNA helicase causes the two strands of DNA to unwind, producing two template strands.

3' (old) A G

A T

C G

C G

G C

C

G C A T

G

G T G A

G T C A

C G C C

T A

T

T G C

A

G

G

G

T

G

T

5' (old)

A

5' (new)

A T A

A T

3' (new)

T

3' (old)

A C A C

G C

A T

A

T A

T

T A

G G A C C T

G C G

G C

A T

C

C G

T G C A A

5' (old)

STEP 4 The other strand is formed in short segments (Okazaki fragments) in the 3'-to-5' direction. The segments are then joined together by DNA ligase.

The most abundant type of RNA in a cell is ribosomal RNA (75% to 80% by mass). Transfer RNA constitutes 10%–15% of cellular RNA; messenger RNA and its precursor, heterogeneous nuclear RNA, make up 5%–10% of RNA material in the cell.

Heterogeneous nuclear RNA (hnRNA) is RNA formed directly by DNA transcription. Post-transcription processing converts the heterogeneous nuclear RNA to messenger RNA. Messenger RNA (mRNA) is RNA that carries instructions for protein synthesis (genetic information) to the sites for protein synthesis. The molecular mass of messenger RNA varies with the length of the protein whose synthesis it will direct. Small nuclear RNA (snRNA) is RNA that facilitates the conversion of heterogeneous nuclear RNA to messenger RNA. It contains from 100 to 200 nucleotides.

22.8 Transcription: RNA Synthesis

Figure 22.13 A hairpin loop is produced when single-stranded RNA doubles back on itself and complementary base pairing occurs.

Hairpin loop

G

U

C A Hydrogen bonds

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G

G

G

U

C

C

C

U

A

G

C

C

C

C

A

G

G

G

A

U

C

G

U A C

G A U

An additional role for RNA, besides its major involvement in protein synthesis, has been recently discovered by scientists. It also plays a part in the process of blood coagulation near a wound. RNA that is released from damaged cells associated with the wound helps to activate two enzymes needed for the blood coagulation process. B

F

A detailed look at cellular structure is found in Section 23.2.

Ribosomal RNA (rRNA) is RNA that combines with specific proteins to form ribosomes, the physical sites for protein synthesis. Ribosomes have molecular masses on the order of 3 million amu. The rRNA present in ribosomes has no informational function. Transfer RNA (tRNA) is RNA that delivers amino acids to the sites for protein synthesis. Transfer RNAs are the smallest of the RNAs, possessing only 75–90 nucleotide units. At a nondetail level, a cell consists of a nucleus and an extranuclear region called the cytoplasm. The process of DNA transcription occurs in the nucleus, as does the processing of hnRNA to mRNA. [DNA replication (Section 22.5) also occurs in the nucleus.] The mRNA formed in the nucleus travels to the cytoplasm where translation (protein synthesis) occurs. Figure 22.14 summarizes the transcription and translation processes in terms of the types of RNA involved and the cellular locations where the processes occur.

22.8 TRANSCRIPTION: RNA SYNTHESIS Transcription is the process by which DNA directs the synthesis of hnRNA/mRNA molecules that carry the coded information needed for protein synthesis. Messenger RNA production via transcription is actually a “two-step” process in which an hnRNA molecule is initially produced and then is “edited” to yield the desired mRNA molecule. The mRNA molecule so produced then functions as the carrier of the information needed to direct protein synthesis. Within a strand of a DNA molecule are instructions for the synthesis of numerous hnRNA/mRNA molecules. During transcription, a DNA molecule unwinds, under enzyme influence, at the particular location where the appropriate base sequence is found for the hnRNA/mRNA of concern, and the “exposed” base sequence is transcribed. A short segment of a DNA strand so transcribed, which contains instructions for the formation of a particular hnRNA/mRNA, is called a gene. A gene is a segment of a DNA strand that contains the base sequence for the production of a specific hnRNA/mRNA molecule. In humans, most genes are composed of 1000–3500 nucleotide units. Hundreds of genes can exist along a DNA strand. Obtaining information concerning the total number of genes and the total number of nucleotide base pairs present in human DNA has been an area of intense research activity for the last two decades. The central activity in this research has been the Human Genome Project, a decade-long internationally based research project to determine the location and base sequence of each of the genes in the human genome. A genome is all of the genetic material (the total DNA) contained in the chromosomes of an organism.

Figure 22.14 An overview of types of RNA in terms of cellular locations where they are encountered and processes in which they are involved.

Cell nucleus

Cytoplasm

plication Re

Transcription DNA hnRNA

Translation Protein

mRNA snRNA

mRNA

mRNA

rRNA

tRNA

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Chapter 22 Nucleic Acids

Before the Human Genome Project began, current biochemical thought predicted the presence of about 100,000 genes in the human genome. Initial results of the human genome project, announced in 2001, pared this number down to 30,000–40,000 genes and also indicated that the base pairs present in these genes constitute only a very small percentage (2%) of the 2.9 billion base pairs present in the chromosomes of the human genome. In 2004, based on reanalysis of human genome project information, the human gene count was pared down further to 20,000–25,000 genes. (Later in this section, the significance and ramifications of this dramatic decrease in estimates of the human gene count are considered.)

Steps in the Transcription Process The mechanics of transcription are in many ways similar to those of DNA replication. Four steps are involved.

In DNA–RNA base pairing, the complementary base pairs are DNA RNA A—U G—C C—G T—A RNA molecules contain the base U instead of the base T.

1. A portion of the DNA double helix unwinds, exposing some bases (a gene). The unwinding process is governed by the enzyme RNA polymerase rather than by DNA helicase (replication enzyme). 2. Free ribonucleotides, one nucleotide at a time, align along one of the exposed strands of DNA bases, the template strand, forming new base pairs. In this process, U rather than T aligns with A in the base-pairing process. Because ribonucleotides rather than deoxyribonucleotides are involved in the base pairing, ribose, rather than deoxyribose, becomes incorporated into the new nucleic acid backbone. 3. RNA polymerase is involved in the linkage of ribonucleotides, one by one, to the growing hnRNA molecule. 4. Transcription ends when the RNA polymerase enzyme encounters a sequence of bases that is “read” as a stop signal. The newly formed hnRNA molecule and the RNA polymerase enzyme are released, and the DNA then rewinds to re-form the original double helix. Figure 22.15 shows the overall process of transcription of DNA to form hnRNA.

EXAMPLE 22.2 Base Pairing Associated with the Transcription Process

From the base sequence 5⬘ A–T–G–C–C–A 3⬘ in a DNA template strand, determine the base sequence in the hnRNA synthesized from the DNA template strand. Solution

An RNA molecule cannot contain the base T. The base U is present instead. Therefore, U–A base pairing will occur instead of T–A base pairing. The other base-pairing combination, G–C, remains the same. The hnRNA product of the transcription process will therefore be DNA template:

5⬘ A–T–G–C–C–A 3⬘       hnRNA molecule: 3⬘ U–A–C–G–G–U 5⬘ Note that the direction of the hnRNA strand is antiparallel to that of the DNA template. This will always be the case during transcription. It is standard procedure, when writing and reading base sequences for nucleic acids (both DNAs and RNAs), always to specify base sequence in the 5⬘ 9: 3⬘ direction unless otherwise directed. Thus 3⬘ U–A–C–G–G–U 5⬘

becomes

5⬘ U–G–G–C–A–U 3⬘

Practice Exercise 22.2 From the base sequence 5⬘ T–A–A–C–C–T 3⬘ in a DNA template strand, determine the base sequence in the hnRNA synthesized from the DNA template strand. Answer: 3⬘ A–U–U–G–G–A 5⬘ which becomes 5⬘ A–G–G–U–U–A 3⬘

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22.8 Transcription: RNA Synthesis

Initiation sequence

Partial unwinding

5'

Transcription

751

3'

Release and rewinding

hnRNA

+

3'

Termination sequence

5'

DNA

DNA

hnRNA

Figure 22.15 The transcription of DNA to form hnRNA involves an unwinding of a portion of the DNA double helix. Only one strand of the DNA is copied during transcription.

Post-Transcription Processing: Formation of mRNA The RNA produced from a gene through transcription is hnRNA, the precursor for mRNA. The conversion of hnRNA to mRNA involves post-transcription processing of the hnRNA. In this processing, certain portions of the hnRNA are deleted and the retained parts are then spliced together. This process leads us to the concepts of exons and introns. It is now known that not all bases in a gene convey genetic information. Instead, a gene is segmented; it has portions called exons that contain genetic information and portions called introns that do not convey genetic information. An exon is a gene segment that conveys (codes for) genetic information. Exons are DNA segments that help express a genetic message. An intron is a gene segment that does not convey (code for) genetic information. Introns are DNA segments that interrupt a genetic message. A gene consists of alternating exon and intron segments (Figure 22.16). Both the exons and the introns of a gene are transcribed during production of hnRNA. The hnRNA is then “edited,” under enzyme direction, to remove the introns, and the remaining exons are joined together to form a shortened RNA strand that carries the genetic information of the transcribed gene. The removal of the introns and joining together of the exons takes place simultaneously in a single process. The “edited” RNA so produced is the messenger RNA (mRNA) that serves as a blueprint for protein assembly. Much is yet to be learned about introns and why they are present in genes; investigating their function is an active area of biochemical research. Splicing is the process of removing introns from an hnRNA molecule and joining the remaining exons together to form an mRNA molecule. The splicing process involves snRNA Figure 22.16 Heterogeneous

Exon

Intron

Exon

Intron

Exon hnRNA

nuclear RNA contains both exons and introns. Messenger RNA is heterogeneous nuclear RNA from which the introns have been excised.

snRNA Introns are cut out.

Section removed

Section removed snRNA

Exons are joined together.

mRNA

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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molecules, the most recent of the RNA types to be discovered. This type of RNA is never found “free” in a cell. An snRNA molecule is always found complexed with proteins in particles called small nuclear ribonucleoprotein particles, which are usually called snRNPs (pronounced “snurps”). A small nuclear ribonucleoprotein particle is a complex formed from an snRNA molecule and several proteins. “Snurps” always further collect together into larger complexes called spliceosomes. A spliceosome is a large assembly of snRNA molecules and proteins involved in the conversion of hnRNA molecules to mRNA molecules.

Alternative Splicing Prior to the announcement of the Human Genome Project’s results, biochemistry had largely embraced the “one-protein-one-gene” concept. It was generally assumed that each type of protein had “its own” gene that carried the instructions for its synthesis. This is no longer plausible because the estimated number of different proteins present in the human body now significantly exceeds the estimated number of genes. The concept of alternative splicing bridges the gap between the larger estimated number of proteins and the now-lower estimated number of genes. Alternative splicing is a process by which several different proteins that are variations of a basic structural motif can be produced from a single gene. In alternative splicing, an hnRNA molecule with multiple exons present is spliced in several different ways. Figure 22.17 shows the four alternative splicing patterns that can occur when an hnRNA contains four exons, two of which are alternative exons.

The Human Transcriptome

Completion of the Human Genome Project is not the end to high-profile cooperative international study of the human genome. A new multiyear, perhaps multidecade, project called ENCODE (encyclopedia of DNA elements) is in its initial stages. The focus of this new project is identification of functional elements within the genome. Functional elements not only include base sequences that code for proteins, but also regulatory sequences that control DNA transcription, and sequences that control the packaging of the genome.

Figure 22.17 An hnRNA molecule containing four exons, two of which (B and C) are alternative exons, can be spliced in four different ways, producing four different proteins. Proteins can be produced with neither, either, or both of the alternative exons present.

As biochemists were mapping the human genome, they anticipated that they were close to unlocking many secrets of the human body and that the results of the project would provide a list of human genes for which the function of each could be quickly investigated. The results of the project, however, only complicated the situation. Results indicate that the total number of genes present in a genome is not as important in understanding human cell behavior as was previously thought, while mRNA transcripts obtained from the genes are more important in understanding human cell behavior than was previously thought. Because of alternative splicing, different cell types interpret the information encoded on a DNA molecule differently and so produce a different number of mRNA molecules and ultimately a different number of proteins. For each cell type, the number of mRNA transcripts generated varies in response to complex signals within a cell and between cells. Research now shows that the information-bearing sections of DNA within a gene can be spliced together an average of eight different ways. There could turn out to be around 200,000 relevant mRNA molecules as compared to 20,000–25,000 genes within the human genome. Collectively, the total number of mRNA molecules for an organism is known as its transcriptome. A transcriptome is all of the mRNA molecules that can be generated from the genetic material in a genome. A transcriptome differs from a genome in that it acknowledges the biochemical complexity created by splice variants obtained from hnRNA. Transcriptome research is now a developing biochemical frontier.

mRNA for second protein

mRNA for first protein

Intron

Intron

Intron hnRNA

Exon A

mRNA for third protein

Exon B

Exon C

Exon D

mRNA for fourth protein

22.9 The Genetic Code

There is a rough correlation between the number of codons for a particular amino acid and that amino acid’s frequency of occurrence in proteins. For example, the two amino acids that have a single codon, Met and Trp, are two of the least common amino acids in proteins.

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22.9 THE GENETIC CODE The nucleotide (base) sequence of an mRNA molecule is the informational part of such a molecule. This base sequence in a given mRNA determines the amino acid sequence for the protein synthesized under that mRNA’s direction. How can the base sequence of an mRNA molecule (which involves only 4 different bases—A, C, G, and U) encode enough information to direct proper sequencing of 20 amino acids in proteins? If each base encoded for a particular standard amino acid, then only 4 amino acids would be specified out of the 20 needed for protein synthesis, a clearly inadequate number. If two-base sequences were used to code amino acids, then there would be 42  16 possible combinations, so 16 amino acids could be represented uniquely. This is still an inadequate number. If three-base sequences were used to code for amino acids, there would be 43  64 possible combinations, which is more than enough combinations for uniquely specifying each of the 20 standard amino acids found in proteins. Research has verified that sequences of three nucleotides in mRNA molecules specify the amino acids that go into synthesis of a protein. Such three-nucleotide sequences are called codons. A codon is a three-nucleotide sequence in an mRNA molecule that codes for a specific amino acid. Which amino acid is specified by which codon? (We have 64 codons to choose from.) Researchers deciphered codon–amino acid relationships by adding different synthetic mRNA molecules (whose base sequences were known) to cell extracts and then determining the structure of any newly formed protein. After many such experiments, researchers finally matched all 64 possible codons with their functions in protein synthesis. It was found that 61 of the 64 codons formed by various combinations of the bases A, C, G, and U were related to specific amino acids; the other 3 combinations were termination codons (“stop” signals) for protein synthesis. Collectively, these relationships between three-nucleotide sequences in mRNA and amino acid identities are known as the genetic code. The genetic code is the assignment of the 64 mRNA codons to specific amino acids (or stop signals). The determination of this code during the early 1960s is one of the most remarkable of twentieth-century scientific achievements. The 1968 Nobel Prize in chemistry was awarded to Marshall Nirenberg and Har Gobind Khorana for their work in illuminating how mRNA encodes for proteins. The complete genetic code is given in Table 22.2. Examination of this table indicates that the genetic code has several remarkable features. 1. The genetic code is highly degenerate; that is, many amino acids are designated by more than one codon. Three amino acids (Arg, Leu, and Ser) are represented by six codons. Two or more codons exist for all other amino acids except Met and Trp, which have only a single codon. Codons that specify the same amino acid are called synonyms. 2. There is a pattern to the arrangement of synonyms in the genetic code table. All synonyms for an amino acid fall within a single box in Table 22.2, unless there are more than four synonyms, where two boxes are needed. The significance of the “single box” pattern is that with synonyms, the first two bases of the codon are the same— they differ only in the third base. For example, the four synonyms for the amino acid proline (Pro) are CCU, CCC, CCA, and CCG. 3. The genetic code is almost universal. Although Table 22.2 does not show this feature, studies of many organisms indicate that with minor exceptions, the code is the same in all of them. The same codon specifies the same amino acid whether the cell is a bacterial cell, a corn plant cell, or a human cell. 4. An initiation codon exists. The existence of “stop” codons (UAG, UAA, and UGA) suggests the existence of “start” codons. There is one initiation codon. Besides coding for the amino acid methionine, the codon AUG functions as an initiator of protein synthesis when it occurs as the first codon in an amino acid sequence.

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TABLE 22.2 The Universal Genetic Code The code is composed of 64 three-nucleotide sequences (codons), which can be read from the table. The left-hand column indicates the nucleotide base found in the first (5⬘) position of the codon. The nucleotide in the second (middle) position of the codon is given by the base listing at the top of the table. The right-hand column indicates the nucleotide found in the third (3⬘) position. Thus the codon ACG encodes for the amino acid Thr, and the codon GGG encodes for the amino acid Gly.

Second letter

First letter (5' end)

U

C

A

G

UUU UUC

Phenylalanine Phe

UUA UUG

Leucine Leu

CUU CUC CUA CUG

Leucine Leu

UCU UCC UCA UCG

CCU CCC CCA CCG

Isoleucine Ile Methionine Met AUG Initiation codon

ACU ACC ACA ACG

GUU GUC GUA GUG

GCU GCC GCA GCG

AUU AUC AUA

EXAMPLE 22.3 Using the Genetic Code and mRNA Codons to Predict Amino Acid Sequences

A

C

Valine Val

Serine Ser

Proline Pro

Threonine Thr

Alanine Ala

G

UAU UAC

Tyrosine Tyr

UGU UGC

Cysteine Cys

UAA UAG

Stop codon Stop codon

UGA

Stop codon Tryptophan Trp

CAU CAC

Histidine His

CAA CAG

Glutamine Gln

CGU CGC CGA CGG

Arginine Arg

AAU AAC

Asparagine Asn

AGU AGC

Serine Ser

U

AAA AAG

Lysine Lys

AGA AGG

Arginine Arg

A

GAU GAC

Aspartic acid Asp

GAA GAG

Glutamic acid Glu

GGU GGC GGA GGG

Glycine Gly

UGG

U C A G U C A G

C

Third letter (3' end)

U

G U C A G

Using the genetic code in Table 22.2, determine the sequence of amino acids encoded by the mRNA codon sequence 5⬘ GCC–AUG–GUA–AAA–UGC–GAC–CCA 3⬘ Solution

Matching the codons with the amino acids, using Table 22.2, yields mRNA: 5⬘ GCC–AUG–GUA–AAA–UGC–GAC–CCA 3⬘ Peptide: Ala Met Val Lys Cys Asp Pro

Practice Exercise 22.3 Using the genetic code in Table 22.2, determine the sequence of amino acids encoded by the mRNA codon sequence 5⬘ CAU–CCU–CAC–ACU–GUU–UGU–UGG 3⬘ Answer: His–Pro–His–Thr–Val–Cys–Trp

22.9 The Genetic Code

EXAMPLE 22.4 Relating Exons and Introns to hnRNA and mRNA Structures

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Sections A, C, and E of the following base sequence section of a DNA template strand are exons, and sections B and D are introns. DNA 5⬘ ATT – CGT – TGT – TTT – CCC – AGT – GCC 3⬘ A B C D E a. What is the structure of the hnRNA transcribed from this template? b. What is the structure of the mRNA obtained by splicing the hnRNA? Solution

Introns and exons are actually never as short as those given in this simplified example.

a. The base sequence in the hnRNA will be complementary to that of the template DNA, except that U is used in the RNA instead of T. The hnRNA will have a directionality antiparallel to that of the DNA sequence. hnRNA

3⬘ UAA – GCA – ACA – AAA – GGG – UCA – CGG 5⬘

b. In the splicing process, introns are removed and the exons combined to give the mRNA. mRNA

3⬘ UAA – ACA – AAA – CGG 5⬘

Practice Exercise 22.4 Sections A, C, and E of the following base sequence section of a DNA template strand are exons, and sections B and D are introns. DNA

5⬘ CGC – CGT – AGT – TGG – CCC – GGA – GGA 3⬘ A B C D E

a. What is the structure of the hnRNA transcribed from this template? b. What is the structure of the mRNA obtained by splicing the hnRNA? Answers: a. 3⬘ GCG–GCA–UCA–ACC–GGG–CCU–CCU 5⬘;

EXAMPLE 22.5 Relating Protein Amino Acid Sequence to the Directionality of an mRNA Segment

b. 3⬘ GCG–ACC–CCU–CCU 5⬘

The structure of an mRNA segment obtained from a DNA template strand is mRNA

3⬘ AUU – CCG – UAC – GAC 5⬘

What polypeptide amino acid sequence will be synthesized using this mRNA? Solution

The directionality of an mRNA segment obtained from template DNA is 3⬘-to-5⬘ because the two segments must be antiparallel to each other (Section 22.5). The codons in an mRNA must be read in the 5⬘-to-3⬘ direction to correctly use genetic code relationships to determine the sequence of amino acids in the peptide. Rewriting the given mRNA with reversed directionality (5⬘-to-3⬘ direction) gives mRNA

5⬘ CAG – CAU – GCC – UUA 3⬘

Note that in reversing the directionality from 3⬘-to-5⬘ to 5⬘-to-3⬘ the sequence of bases in a codon is also reversed; for example, GAC becomes CAG. Using the genetic code relationships between codon and amino acid (Table 22.2) shows that this mRNA codon sequence codes for the amino acid sequence

Gln–His–Ala–Leu (continued)

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Chapter 22 Nucleic Acids

Practice Exercise 22.5 The structure of an mRNA segment obtained from a DNA template strand is mRNA

3⬘ ACG – AGC – CCU – CUU 5 ⬘

What polypeptide amino acid sequence will be synthesized using this mRNA? Answer: Phe–Ser–Arg–Ala

22.110 ANTICODONS AND tRNA MOLECULES 22. The amino acids used in protein synthesis do not directly interact with the codons of an mRNA molecule. Instead, tRNA molecules function as intermediaries that deliver amino acids to the mRNA. At least one type of tRNA molecule exists for each of the 20 amino acids found in proteins. All tRNA molecules have the same general shape, and this shape is crucial to how they function. Figure 22.18a shows the general two-dimensional “cloverleaf” shape of a tRNA molecule, a shape produced by the molecule’s folding and twisting into regions of parallel strands and regions of hairpin loops. (The actual three-dimensional shape of a tRNA molecule involves considerable additional twisting of the “cloverleaf” shape— Figure 22.18b.) Two features of the tRNA structure are of particular importance. 1. The 3⬘ end of the open part of the cloverleaf structure is where an amino acid becomes covalently bonded to the tRNA molecule through an ester bond. Each of the different tRNA molecules is specifically recognized by an aminoacyl tRNA synthetase enzyme. These enzymes also recognize the one kind of amino acid that “belongs” with the particular tRNA and facilitates its bonding to the tRNA (see Figure 22.19). 2. The loop opposite the open end of the cloverleaf is the site for a sequence of three bases called an anticodon. An anticodon is a three-nucleotide sequence on a tRNA molecule that is complementary to a codon on an mRNA molecule.

Figure 22.18 A tRNA molecule. The amino acid attachment site is at the open end of the cloverleaf (the 3⬘ end), and the anticodon is located in the hairpin loop opposite the open end.

Amino acid attachment site

A C C G U A G C G U G C CAG A C C GGUC C A U G U C U C A G U

3' end 5' end 5' end

3' end

A U C G C UAAG G C

C

GUUC C U A G A G U C C

C A C U U

G G A

Anticodon

Anticodon (a)

(b)

22.10 Anticodons and tRNA Molecules

Figure 22.19 An aminoacyl–tRNA synthetase has an active site for tRNA and a binding site for the particular amino acid that is to be attached to that tRNA.

O +

757

OH

CH C O–

H3N

CH2

Aminoacyl–tRNA synthetase specific for histidine

NH N

Active site for histidine

Active site for tRNAHistidine

The interaction between the anticodon of the tRNA and the codon of the mRNA leads to the proper placement of an amino acid into a growing peptide chain during protein synthesis. This interaction, which involves complementary base pairing, is shown in Figure 22.20.

EXAMPLE 22.6 Determining Codon–Anticodon Relationships

A tRNA molecule has the anticodon 5 AAG 3. With which mRNA codon will this anticodon interact? Solution

The interaction between a codon and an anticodon has directionality (antiparallel) considerations, that is, Amino acid 3'

5'

3

Anticodon

5

5

Codon

3

The given anticodon, with reversed directionality, is 3 GAA 5

and its codon interaction, which involves complementary base pairing, is tRNA

5'

3 GAA 5

Codon

5 CUU 3

The codon is, thus, 5 CUU 3.

Anticodon A G U U C A

mRNA

Anticodon

3'

Codon

Figure 22.20 The interaction between anticodon (tRNA) and codon (mRNA), which involves complementary base pairing, governs the proper placement of amino acids in a protein.

EXAMPLE 22.7 Determining Anticodon–tRNA Amino Acid Relationships

Practice Exercise 22.6 A tRNA molecule has the anticodon 5 ACG 3. With which mRNA codon will this anticodon interact? Answer: 5 CGU 3

A tRNA molecule possesses the anticodon 5 CGU 3. Which amino acid will this tRNA molecule carry? Solution

Codons, rather than anticodons, are involved in the genetic code relationships. The codon with which this anticodon 5 CGU 3 base pairs is 5 ACG 3. Remember, as shown in (continued)

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Chapter 22 Nucleic Acids

Example 22.6, that the codon–anticodon pairing involves the anticodon 3⬘ UGC 5⬘ (the anticodon written in the 3⬘-to-5⬘ direction). Anticodon

3⬘ UGC 5⬘

Codon

5⬘ ACG 3⬘

The amino acid that the codon ACG codes for (see Table 22.2) is Thr (Threonine).

Practice Exercise 22.7 A tRNA molecule possesses the anticodon 5⬘ UGA 3⬘. Which amino acid will this tRNA molecule carry? Answer: Ser (Serine)

22.111 TRANSLATION: PROTEIN SYNTHESIS 22.1 Translation is the process by which mRNA codons are deciphered and a particular protein molecule is synthesized. The substances needed for the translation phase of protein synthesis are mRNA molecules, tRNA molecules, amino acids, ribosomes, and a number of different enzymes. A ribosome is an rRNA–protein complex that serves as the site for the translation phase of protein synthesis. The number of ribosomes present in a cell for higher organisms varies from hundreds of thousands to even a few million. Recent research concerning ribosome structure suggests the following for such structures: 1. They contain four rRNA molecules and about 80 proteins that are packed into two rRNA-protein subunits, one small subunit and one large subunit (see Figure 22.21). 2. Each subunit contains approximately 65% rRNA and 35% protein by mass. 3. A ribosome’s active site, the location where proteins are synthesized by one-at-atime addition of amino acids to a growing peptide chain, is located in the large ribosomal subunit. 4. The active site is mostly rRNA, with only one of the ribosome’s many protein components being present. 5. Because rRNA is so predominant at the active site, the ribosome is thought to be a RNA enzyme (Section 21.1), that is, a ribozyme. 6. The mRNA involved in the translation phase of protein synthesis binds to the small subunit of the ribosome. There are five general steps to the translation process: (1) activation of tRNA, (2) initiation, (3) elongation, (4) termination, and (5) post-translational processing.

Figure 22.21 Ribosomes, which contain both rRNA and protein, have structures that contain two subunits. One subunit is much larger than the other.

Ribosomal subunits

Large subunit

Ribosome Small subunit

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22.11 Translation: Protein Synthesis

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Activation of tRNA There are two steps involved in tRNA activation. First, an amino acid interacts with an activator molecule (ATP; Section 23.3) to form a highly energetic complex. This complex then reacts with the appropriate tRNA molecule to produce an activated tRNA molecule, a tRNA molecule that has an amino acid covalently bonded to it at its 3 end through an ester linkage. OH

R

5'

H

O

C

C

Ester linkage O

5'

NH + 3

tRNA (unactivated tRNA)

Acylamino tRNA (activated tRNA)

Initiation The initiation of protein synthesis in human cells begins when mRNA attaches itself to the surface of a small ribosomal subunit such that its first codon, which is always the initiating codon AUG, occupies a site called the P site (peptidyl site). (See Figure 22.22a.) An activated tRNA molecule with anticodon complementary to the codon AUG attaches itself, through complementary base pairing, to the AUG codon (Figure 22.22b). The resulting complex then interacts with a large ribosomal subunit to complete the formation of an initiation complex (Figure 22.22c). (Since the initiating codon AUG codes for the amino acid methionine, the first amino acid in a developing human protein chain will always be methionine.)

Elongation Next to the P site in an mRNA–ribosome complex is a second binding site called the A site (aminoacyl site). (See Figure 22.23a.) At this second site the next mRNA codon is exposed, and a tRNA with the appropriate anticodon binds to it (Figure 22.23b). With amino acids in place at both the P and the A sites, the enzyme peptidyl transferase effects the linking of

Figure 22.22 Initiation of protein synthesis begins with the formation of an initiation complex.

Met

Met

3'

3'

5'

5'

Initiating codon at P site AUG

mRNA 5'

UA C

UA C

AUG

AUG

3' P site Small subunit (a)

Large subunit 3'

3' 5'

P site

(b)

P site

5' (c)

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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Met

tRNA carrying an amino acid Anticodon

Ribosome UA C

AUG

Gly

Met

Codons

GGU

5'

G C U

UUU

GGU

C UG

C AU

C C A

AUG

GGU

3' 5'

mRNA

A site

UA C

UUU

(a)

C UG

C AU

3'

(b)

The initiation tRNA carrying the amino acid Met binds at the P site.

A tRNA with amino acid 2 binds at the A site.

Ala

Met

Ala

Met

GGU

A site

P site

P site

G C U

Gly

Gly

C UA

CG A

5'

P site

UA C

C C A

AUG

GGU

C GA C C A

G C U

UUU

GGU

C UG

C AU

G AU

3' 5'

A site

GGU

G C U

P site

UUU

GGU

C UG

C AU

3'

A site

(c)

(d)

A peptide bond forms between amino acid 1 and amino acid 2 as amino acid 1 moves from the P site to the A site.

The first tRNA is released, the ribosome moves one codon to the right, translocating the dipeptide to the P site, and the tRNA with amino acid 3 occupies the A site. Met Gly

Ala

C C A

C GA

GGU

G C U

Phe

A

AUG

Figure 22.23 The process of translation that occurs during protein synthesis. The anticodons of tRNA molecules are paired with the codons of an mRNA molecule to bring the appropriate amino acids into sequence for protein formation.

In elongation, the polypeptide chain grows one amino acid at a time.

The process of translocation occurs at approximately 50-millisecond intervals, that is, 20 times per second.

5'

P site

A

A

UUU

GGU

C UG

C AU

3'

A site (e)

Elongation continues as the dipeptide at the P site is bonded to the amino acid at the A site to form a tripeptide.

the P site amino acid to the A site amino acid to form a dipeptide. Such peptide bond formation leaves the tRNA at the P site empty and the tRNA at the A site bearing the dipeptide (Figure 22.23c). The empty tRNA at the P site now leaves that site and is free to pick up another molecule of its specific amino acid. Simultaneously with the release of tRNA from the P site, the ribosome shifts along the mRNA. This shift puts the newly formed dipeptide at the P site, and the third codon of mRNA is now available, at site A, to accept a tRNA molecule whose anticodon complements this codon (see Figure 22.23d). The movement of a ribosome along an mRNA molecule is called translocation. Translocation is the part of translation in which a ribosome moves down an mRNA molecule three base positions (one codon) so that a new codon can occupy the ribosomal A site.

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22.11 Translation: Protein Synthesis

c

761

HEMICAL

onnections

Antibiotics That Inhibit Bacterial Protein Synthesis

Some antibiotics work because they inhibit protein synthesis in bacteria but not in humans. They inhibit one specific enzyme or another in the bacterial ribosomes. These antibiotics are useful in treating disease and in studying protein synthesis mecha-

nisms in bacteria. The accompanying table lists a few of the most commonly encountered antibiotics and their modes of action relative to protein synthesis.

Antibiotic

Biological Action

Antibiotic

Biological Action

chloramphenicol

inhibits an important enzyme (peptidyl transferase) in the large ribosomal subunit

streptomycin

inhibits initiation of protein synthesis and also causes the mRNA codons to be read incorrectly

erythromycin

binds to the large subunit and stops the ribosome from moving along the mRNA from one codon to the next

tetracycline

binds to the small ribosomal subunit and inhibits the binding of incoming tRNA molecules

puromycin

induces premature polypeptide chain termination

Now a repetitious process begins. The third codon, now at the A site, accepts an incoming tRNA with its accompanying amino acid; and then the entire dipeptide at the P site is transferred and bonded to the A site amino acid to give a tripeptide (see Figure 22.23e). The empty tRNA at the P site is released, the ribosome shifts along the mRNA, and the process continues. The transfer of the growing peptide chain from the P site to the A site is an example of an acyl transfer reaction, a reaction type first introduced in Section 16.19. Figure 22.24 shows the structural detail for such transfer when Met is the amino acid at the P site and Gly is the amino acid at the A site.

NH2 CH3

Acyl group CH3

S

CH2

CH2 O

CH2

CH2 O

C

Gly

NH2

NH2

NH

CH

CH2

CH2

C

C

O

O

O

C

Acyl transfer reaction

UA C

C C C

AUG

GGG

5'

AU C

mRNA P site

OH

Met

CH

Met

tRNA Ribosome

S

Gly O

O

Empty tRNA UA C

C C C

AUG

GGG

3'

AU C

3'

5'

A site

P site

A site

Figure 22.24 The transfer of an amino acid (or growing peptide chain) from the ribosomal P site to the ribosomal A site during translation is an example of an acyl transfer reaction.

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Chapter 22 Nucleic Acids

Termination The polypeptide continues to grow by way of translocation until all necessary amino acids are in place and bonded to each other. Appearance in the mRNA codon sequence of one of the three stop codons (UAA, UAG, or UGA) terminates the process. No tRNA has an anticodon that can base-pair with these stop codons. The polypeptide is then cleaved from the tRNA through hydrolysis.

Post-Translation Processing Some modification of proteins usually occurs after translation. This post-translation processing gives the protein the final form it needs to be fully functional. Some of the aspects of post-translation processing are the following. 1. In most proteins, the methionine (Met) residue that initiated protein synthesis is removed by a specialized enzyme in a hydrolysis reaction. A second hydrolysis reaction releases the polypeptide chain from its tRNA carrier. 2. Some covalent modification of a protein can occur, such as the formation of disulfide bridges between cysteine residues (Section 20.5). 3. Completion of the folding of polypeptides into their active conformations occurs. Protein folding actually begins as the polypeptide chain is elongated on the ribosome. For protein with quaternary structure (Section 20.12), the various components are assembled together. Recent research indicates that there may be a connection between synonymous codons within the genetic code (Section 22.9) and protein folding. It now appears that synonymous codons, even though they translate into the same amino acids during protein synthesis, have an effect on the way emerging proteins fold into their three-dimensional shapes (tertiary structure; Section 20.11) as they elongate and then leave a ribosome. This means that two stretches of mRNA that differ only in synonymous codons can produce proteins with identical amino acid sequences but different folding patterns. Two differently folded proteins would be expected to produce different biochemical responses within a cell when interacting with other substances; there is some evidence, now, that this is the case.

Efficiency of mRNA Utilization Many ribosomes can move simultaneously along a single mRNA molecule (Figure 22.25). In this highly efficient arrangement, many identical protein chains can be synthesized almost at the same time from a single strand of mRNA. This multiple use of mRNA molecules reduces the amount of resources and energy that the cell expends to synthesize needed protein. Such complexes of several ribosomes and mRNA are called polyribosomes or polysomes. A polyribosome is a complex of mRNA and several ribosomes. The Chemistry at a Glance feature on page 764 summarizes the steps in protein synthesis.

Figure 22.25 Several ribosomes can simultaneously proceed along a single strand of mRNA one after another. Such a complex of mRNA and ribosomes is called a polyribosome or polysome.

Large subunit of ribosome

Growing Secondary structure protein begins to form.

Ribosome 3' subunits are released.

mRNA 5' Ribosomes move along mRNA. Small subunit of ribosome

Complete protein

22.13 Nucleic Acids and Viruses

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22.112 MUTATIONS 22. A mutation is an error in base sequence in a gene that is reproduced during DNA replication. Such errors alter the genetic information that is passed on during transcription. The altered information can cause changes in amino acid sequence during protein synthesis. Sometimes, such changes have a profound effect on an organism. A mutagen is a substance or agent that causes a change in the structure of a gene. Radiation and chemical agents are two important types of mutagens. Radiation, in the form of ultraviolet light, X rays, radioactivity (Chapter 11), and cosmic rays, has the potential to be mutagenic. Ultraviolet light from the sun is the radiation that causes sunburn and can induce changes in the DNA of the skin cells. Sustained exposure to ultraviolet light can lead to serious problems such as skin cancer. Chemical agents can also have mutagenic effects. Nitrous acid (HNO2) is a mutagen that causes deamination of heterocyclic nitrogen bases. For example, HNO2 can convert cytosine to uracil. NH2

O H

N N A H

N

HNO2

O

Cytosine

N A H

O

Uracil

Deamination of a cytosine that was part of an mRNA codon would change the codon; for example, CGG would become UGG. A variety of chemicals—including nitrites, nitrates, and nitrosamines—can form nitrous acid in the body. The use of nitrates and nitrites as preservatives in foods such as bologna and hot dogs is a cause of concern because of their conversion to nitrous acid in the body and possible damage to DNA. Fortunately, the body has repair enzymes that recognize and replace altered bases. Normally, the vast majority of altered DNA bases are repaired, and mutations are avoided. Occasionally, however, the damage is not repaired, and the mutation persists.

22.113 NUCLEIC ACIDS AND VIRUSES 22.

Figure 22.26 An electron microscope image of an influenza virus.

Viruses are very small disease-causing agents that are considered the lowest order of life. Indeed, their structure is so simple that some scientists do not consider them truly alive because they are unable to reproduce in the absence of other organisms. Figure 22.26 shows an electron microscope image of an influenza virus. A virus is a small particle that contains DNA or RNA (but not both) surrounded by a coat of protein and that cannot reproduce without the aid of a host cell. Viruses do not possess the nucleotides, enzymes, amino acids, and other molecules necessary to replicate their nucleic acid or to synthesize proteins. To reproduce, viruses must invade the cells of another organism and cause these host cells to carry out the reproduction of the virus. Such an invasion disrupts the normal operation of cells, causing diseases within the host organism. The only function of a virus is reproduction; viruses do not generate energy. There is no known form of life that is not subject to attack by viruses. Viruses attack bacteria, plants, animals, and humans. Many human diseases are of viral origin. Among them are the common cold, mumps, measles, smallpox, rabies, influenza, infectious mononucleosis, hepatitis, and AIDS. Viruses most often attach themselves to the outside of specific cells in a host organism. An enzyme within the protein overcoat of the virus catalyzes the breakdown of the cell membrane, opening a hole in the membrane. The virus then injects its DNA or RNA into the cell. Once inside, this nucleic acid material is mistaken by the host cell for its own, whereupon that cell begins to translate and/or transcribe the viral nucleic acid. When all

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Chapter 22 Nucleic Acids

Protein Synthesis: Transcription and Translation TRANSCRIPTION PHASE

Nuclear membrane Nucleus of cell

Step 1: Formation of hnRNA

Step 2: Formation of mRNA

DNA in the nucleus partially unwinds to allow a strand of hnRNA to be made.

TRANSLATION PHASE

3' end

Cytoplasm of cell

Step 3: mRNA Enters the Cytoplasm

Introns are removed from the hnRNA strand.

The mRNA leaves the nucleus and enters the cytoplasm.

Met

A C C G U A G C G U G C CAG A C C GGUC C U A G U C U C A G U

Step 1: Activation of tRNA 5' end

An amino acid interacts with ATP to become highly energized. It then forms a covalent bond with the 3' end of a tRNA molecule. Amino acid– tRNA pairing is governed by enzymes.

A U C G C C G G A GUUC C U A G A G U C C UAAG G C

A C C U U

Anticodon

Val

Met Met

UA C

AUG

mRNA

Gly

Glu

Gly

Ribosome

Ile Met

Gln

Codons

GGU

AU C

UA C

C C A

AUG

GGU

GUU AU C

GAA

C AA

UAA

A site

P site

Step 2: Initiation The mRNA attaches to a ribosome so that the first codon (AUG) is at the P site. A tRNA carrying methionine attaches to the first codon.

Step 3: Elongation Another tRNA with the second amino acid binds at the A site. The methionine transfers from the P site to the A site. The ribosome shifts to the next codon, making its A site available for the tRNA carrying the third amino acid.

Steps 4 and 5: Termination and Post-Translation Processing The polypeptide chain continues to lengthen until a stop codon appears on the mRNA. The new protein is cleaved from the last tRNA. During post-translation processing, cleavage of Met (the initiation codon) usually occurs. S—S bonds between Cys units also can form.

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22.14 Recombinant DNA and Genetic Engineering

Viral infections are more difficult to treat than bacterial infections because viruses, unlike bacteria, replicate inside cells. It is difficult to design drugs that prevent the replication of the virus that do not also affect the normal activities of the host cells.

765

the virus components have been synthesized by the host cell, they assemble automatically to form many new virus particles. Within 20 to 30 minutes after a single molecule of viral nucleic acid enters the host cell, hundreds of new virus particles have formed. So many are formed that they eventually burst the host cell and are free to infect other cells. If a virus contains DNA, the host cell replicates the viral DNA in a manner similar to the way it replicates its own DNA. The newly produced viral DNA then proceeds to make the proteins needed for the production of protein coats for additional viruses. An RNA-containing virus is called a retrovirus. Once inside a host, such viruses first make viral DNA. This reverse synthesis is governed by the enzyme reverse transcriptase. The template is the viral RNA rather than DNA. The viral DNA so produced then produces additional viral DNA and the proteins necessary for the protein coats. The AIDS (acquired immunodeficiency syndrome) virus is an example of a retrovirus. This virus has an affinity for a specific type of white blood cell called a helper T cell, which is an important part of the body’s immune system. When helper T cells are unable to perform their normal functions as a result of such viral infection, the body becomes more susceptible to infection and disease. A vaccine is a preparation containing an inactive or weakened form of a virus or bacterium. The antibodies produced by the body against these specially modified viruses or bacteria effectively act against the naturally occurring active forms as well. Thanks to vaccination programs, many diseases, such as polio and mumps (caused by RNA-containing viruses) and smallpox and yellow fever (caused by DNA-containing viruses), are now seldom encountered.

22.114 RECOMBINANT DNA AND GENETIC ENGINEERING 22. Increased knowledge about how DNA molecules function under various chemical conditions has opened the door to the field of technology called genetic engineering or biotechnology. Techniques now exist whereby a “foreign” gene can be added to an organism, and the organism will produce the protein associated with the added gene. As an example of benefits that can come from genetic engineering, consider the case of human insulin. For many years, because of the very limited availability of human insulin, the insulin used by diabetics was obtained from the pancreases of slaughterhouse animals. Such insulin is structurally very similar to human insulin (see the Chemical Connections feature “Substitutes for Human Insulin” on page 671) and can be substituted for it. Today, diabetics can also choose to use “real” human insulin produced by genetically altered bacteria. Such “genetically engineered” bacteria are grown in large numbers, and the insulin they produce is harvested in a manner similar to the way some antibiotics are obtained from cultured microorganisms. Human growth hormone is another substance that is now produced by genetically altered bacteria. Table 22.3 gives additional

TABLE 22.3 Selected Human Proteins Produced Using Recombinant DNA Technology and Their Uses

Protein

Treatment

insulin erythropoietin (EPO) human growth hormone (HGH) interleukins interferons lung surfactant protein serum albumin tumor necrosis factor (TNF) tissue plasminogen activator (TPA) epidermal growth factor fibroblast growth factor

diabetes anemia stimulate growth stimulate immune system leukemia and other cancers respiratory distress plasma supplement cancers heart attacks healing of wounds and burns ulcers

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Chapter 22 Nucleic Acids

Figure 22.27 Recombinant DNA is made by inserting a gene obtained from DNA of one organism into the DNA from another kind of organism.

Isolated plasmid (bacterial DNA) E. coli bacterium DNA from foreign cell

Desired foreign gene

Plasmids

DNA segment is “opened up” by restriction enzyme. Foreign gene is “clipped out” by restriction enzyme. Recombinant DNA E. coli with recombinant DNA molecules

The notation rDNA is often used to designate recombinant DNA.

Foreign gene and bacterial DNA are spliced together in presence of DNA ligase.

examples of human proteins that are used in therapeutic medicine that have become available through the use of recombinant DNA technology. Genetic engineering procedures involve a type of DNA called recombinant DNA. Recombinant DNA (rDNA) is DNA that contains genetic material from two different organisms. Let us examine the theory and procedures used in obtaining recombinant DNA through genetic engineering. The bacterium E. coli, which is found in the intestinal tract of humans and animals, is the organism most often used in recombinant DNA experiments. Yeast cells are also used, with increasing frequency, in this research. In addition to their chromosomal DNA, E. coli (and other bacteria) contain DNA in the form of small, circular, double-stranded molecules called plasmids. These plasmids, which carry only a few genes, replicate independently of the chromosome. Also, they are transferred relatively easily from one cell to another. Plasmids from E. coli are used in recombinant DNA work. The procedure used to obtain E. coli cells that contain recombinant DNA involves the following steps (see Figure 22.27). Step 1: Step 2:

Step 3:

Step 4: Step 5:

Cell membrane dissolution. E. coli cells of a specific strain are placed in a solution that dissolves cell membranes, thus releasing the contents of the cells. Isolation of plasmid fraction. The released cell components are separated into fractions, one fraction being the plasmids. The isolated plasmid fraction is the material used in further steps. Cleavage of plasmid DNA. A special enzyme, called a restriction enzyme, is used to cleave the double-stranded DNA of a circular plasmid. The result is a linear (noncircular) DNA molecule. Gene removal from another organism. The same restriction enzyme is then used to remove a desired gene from a chromosome of another organism. Gene–plasmid splicing. The gene (from Step 4) and the opened plasmid (from Step 3) are mixed in the presence of the enzyme DNA ligase, which splices the two together. This splicing, which attaches one end of the gene to one end of the

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22.14 Recombinant DNA and Genetic Engineering

Figure 22.28 Cleavage pattern resulting from the use of a restriction enzyme that cleaves DNA between G and A bases in the 5-to-3 direction in the sequence G—A—A—T—T—C. The double-helix structure is not cut straight across.

767

Cleavage point 5'

3' T T GAA T T C T G C A AA C T T AAGA C G T

3'

5'

Cleavage point

T T G AA C T T AA

Step 6:

Sticky ends A A T T C T G C A GA C G T

opened plasmid and attaches the other end of the gene to the other end of the plasmid, results in an altered circular plasmid (the recombinant DNA). Uptake of recombinant DNA. The altered plasmids (recombinant DNA) are placed in a live E. coli culture, where they are taken up by the E. coli bacteria. The E. coli culture into which the plasmids are placed need not be identical to that from which the plasmids were originally obtained.

We noted in Step 3 that the conversion of a circular plasmid into a linear DNA molecule requires a restriction enzyme. A restriction enzyme is an enzyme that recognizes specific base sequences in DNA and cleaves the DNA in a predictable manner at these sequences. The discovery of restriction enzymes made genetic engineering possible. Restriction enzymes occur naturally in numerous types of bacterial cells. Their function is to protect the bacteria from invasion by foreign DNA by catalyzing the cleavage of the invading DNA. The term restriction relates to such enzymes placing a “restriction” on the type of DNA allowed into the bacterial cells. To understand how a restriction enzyme works, let us consider one that cleaves DNA between G and A bases in the 5-to-3 direction in the sequence G–A–A–T–T–C. This enzyme will cleave the double-helix structure of a DNA molecule in the manner shown in Figure 22.28. Note that the double helix is not cut straight across; the individual strands are cut at different points, giving a staircase cut. (Both cuts must be between G and A in the 5-to-3 direction.) This staircase cut leaves unpaired bases on each cut strand. These ends with unpaired bases are called “sticky ends” because they are ready to “stick to” (pair up with) a complementary section of DNA if they can find one. If the same restriction enzyme used to cut a plasmid is also used to cut a gene from another DNA molecule, the sticky ends of the gene will be complementary to those of the plasmid. This enables the plasmid and gene to combine readily, forming a new, modified plasmid molecule. This modified plasmid molecule is called recombinant DNA. In addition to the newly spliced gene, the recombinant DNA plasmid contains all of the genes and characteristics of the original plasmid. Figure 22.29 shows diagrammatically the match between sticky ends that occurs when plasmid and gene combine. Step 6 involves inserting the recombinant DNA (modified plasmids) back into E. coli cells. The process is called transformation. Transformation is the process of incorporating recombinant DNA into a host cell. The transformed cells then reproduce, resulting in large numbers of identical cells called clones. Clones are cells with identical DNA that have descended from a single cell. Within a few hours, a single genetically altered bacterial cell can give rise to thousands of clones. Each clone has the capacity to synthesize the protein directed by the foreign gene it carries. Researchers are not limited to selection of naturally occurring genes for transforming bacteria. Chemists have developed nonenzymatic methods of linking nucleotides

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Chapter 22 Nucleic Acids

Figure 22.29 The “sticky ends” of the cut plasmid and the cut gene are complementary and combine to form recombinant DNA.

Cut gene A A T T T T A A

Complementary sticky ends

G

C

G G A A T T T C TA A

G TT C AA

G

C T T A A

C T T A A

A

T T

A

A

T

A

T

G

C

A A T

G T C

Plasmid

Cut plasmid

T A T A A T A G T C

Recombinant DNA

together such that they can construct artificial genes of any sequence they desire. In fact, benchtop instruments are now available that can be programmed by a microprocessor to synthesize any DNA base sequence automatically. The operator merely enters a sequence of desired bases, starts the instrument, and returns later to obtain the product. Such flexibility in manufacturing DNA has opened many doors, accelerated the pace of recombinant DNA research, and redefined the term designer genes!

22.115 THE POLYMERASE CHAIN REACTION 22. PCR temperature conditions are higher than those in the human body. This is possible because the DNA polymerase used was isolated from an organism that lives in the “hot pots” of Yellowstone National Park at temperatures of 70C–75C.

After n cycles of the PCR process, the amount of DNA will have increased 2n times. 210 is approximately 1000. 220 is approximately 1,000,000. Twenty-five cycles of the PCR can be carried out in an hour in a process that is fully automated.

The polymerase chain reaction (PCR) is a method for rapidly producing multiple copies of a DNA nucleotide sequence. Billions of copies of a specific DNA sequence (gene) can be produced in a few hours via this reaction. The PCR is easy to carry out, requiring only a few chemicals, a container, and a source of heat. (In actuality, the PCR process is now completely automated.) By means of the PCR process, DNA that is available only in very small quantities can be amplified to quantities large enough to analyze. The PCR process, devised in 1983, has become a valuable tool for diagnosing diseases and detecting pathogens in the body. It is now used in the prenatal diagnosis of a number of genetic disorders, including muscular dystrophy and cystic fibrosis, and in the identification of bacterial pathogens. It is also the definitive way to detect the AIDS virus. The PCR process has also proved useful in certain types of forensic investigations. A DNA sample may be obtained from a single drop of blood or semen or a single strand of hair at a crime scene and amplified by the PCR process. A forensic chemist can then compare the amplified samples with DNA samples taken from suspects. Work with DNA in the forensic area is often referred to as DNA fingerprinting. DNA polymerase, an enzyme present in all living organisms, is a key substance in the PCR process. It can attach additional nucleotides to a short starter nucleotide chain, called a primer, when the primer is bound to a complementary strand of DNA that functions as a template. The original DNA is heated to separate its strands, and then primers, DNA polymerase, and deoxyribonucleotides are added so that the DNA polymerase can replicate the original strand. The process is repeated until, in a short time, millions of copies of the original DNA have been made. Figure 22.30 shows diagrammatically, in very simplified terms, the basic steps in the PCR process.

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22.16 DNA Sequencing

Figure 22.30 The basic steps, in simplified terms, of the polymerase chain reaction process. Each cycle of the polymerase chain reaction doubles the number of copies of the target DNA sequence.

Step 1

A DNA solution is heated to cause the base-paired double helix to unwind into single strands.

5'

Target area

3' 90˚C

3'

Target area

5'

Step 2

5'

Target area

3'

3'

Target area

5'

Primers complementary to the DNA on either side of the target area of the single-stranded DNA are added.

5'

3'

Target area

5'

3' 5'

3'

3'

Target area

3' Primer

5'

3' Target area

5'

70˚C

5'

Target area

3'

3'

Target area

5'

5'

Target area

3'

3'

Target area

5'

3'

Primer

3'

5'

Target area

3'

5'

3'

Target area

5'

5'

Target area

3'

3'

3'

Target area

5' Repeat

3'

Target area

5'

5'

Target area

3' cycle

5'

Target area

3'

5'

3'

Target area

5'

5'

Target area

3'

3'

Target area

5'

3' 5' 3'

Primer

Cycle 1

The process is repeated for as many cycles as necessary, and in a short time millions of identical DNA molecules have been produced. Target area

Primer

5'

5'

Target area

5'

5'

Primer

3'

3' Step 4

Primer

Primer

DNA polymerase is used to extend the primers to create segments of DNA identical to the original segment.

5'

5'

3'

5'

Target area

3'

Target area

50˚C

Step 3

769

Primer

3' Target area

5'

Cycle 2

22.116 DNA SEQUENCING 22. DNA sequencing is a method by which the base sequence in a DNA molecule (or a portion of it) is determined. Discovered in 1977, this is the process that made the Human Genome Project (Section 22.8) possible. Today, thanks to computer technology, sequencing a nucleic acid is a fairly routine, fully automated process. The key concept in DNA sequencing is the selective interruption of polynucleotide synthesis. This interruption of synthesis, which is caused to occur at every possible nucleotide site, depends on the presence of 2,3-dideoxyribonucleotide triphosphates (ddNTPs) in the synthesis mixture. Such compounds are synthetic analogs of the standard deoxyribonucleotide triphosphates in which both the 2 and the 3 hydroxy groups of deoxyribose have been replaced by hydrogen substituents. Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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Chapter 22 Nucleic Acids

O ⫺

O

P

O O

⫺

O

P

O O

⫺

O

P ⫺

O

O

CH2 H

O

Base (A, C, G, or T) H

H

H H

H

ddNTPs

The basic steps involved in the DNA sequencing process are as follows: Step 1:

Step 2:

Step 3:

Step 4: Figure 22.31 A schematic diagram of selected steps in the DNA sequencing procedure for the 10-base DNA segment 5⬘ AGCAGCTGGT 3⬘.

(a)

STEP 4

DNA template with primer (b)

STEP 5

Nucleotides present in the four reaction mixtures (c)

Addition of primer to the single strands. The single-stranded DNA to be sequenced (the template) is mixed with short polynucleotides that serve as a primer for the complementary strands (see Figure 22.31a).

3' 5'

CATGGTCGACGA GT

Mixture 1 dATP + ddATP dCTP dGTP dTTP

Template Primer

Mixture 2 dATP dCTP dGTP + ddGTP dTTP

Mixture 3 dATP dCTP + ddCTP dGTP dTTP

Fluorescent marker

Mixture 4 dATP dCTP dGTP dTTP + ddTTP

STEP 6

Complementary strands formed through synthesis interruption (d)

Cleavage using restriction enzymes. Restriction enzymes (Section 22.14) are used to cleave a DNA molecule, which is too large to be sequenced as a whole, into smaller fragments (100–200 base pairs). These smaller fragments are the DNA actually sequenced. By later identifying the points of overlap among the fragments sequenced, it is possible to determine the base sequence of the entire original DNA molecule. Separation into individual components. The mixture of small DNA fragments generated by the restriction enzymes is separated into individual components. Each component type is then sequenced independently. Separation of the fragment mixture is accomplished via gel electrophoresis techniques (Section 20.4). Separation into single strands. Using chemical methods, a given DNA fragment is separated into its two strands, and one strand is then used as a template to create complementary strands of varying lengths via the “interruption of synthesis” process.

GTA GTACCA

GTACCAG GTAC GTACCAGCT GTACCAGCTG GTACC GTACCAGCTGCT GTACCAGC GTACCAGCTGC

STEP 7

Separation using gel electrophoresis

A Largest fragment

Smallest fragment

G

C 10 9 8 7 6 5 4 3 2 1

T

Sequence complementary to template DNA 3' end T C G T C G A C C A 5' end

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Concepts to Remember

Step 5:

Step 6:

Step 7:

c

771

Separation of the reaction mixture into four parts. The mixture of template DNA and primer is divided into four portions, and four parallel synthesis reactions are carried out. Each reaction mixture contains all four deoxyribonucleotide triphosphates: dATP, dCTP, dGTP, and dTTP (Section 22.2). Each test tube also contains a unique ingredient—one of the ddNTPs that has been labeled with a fluorescent material that can be detected using instrumentation (see Figure 22.31b). Polynucleotide synthesis with interruption. As DNA complementary strand synthesis proceeds, nucleotides from the solution are added to the growing polynucleotide chain. Elongation of the growing chain takes place without complication until a ddNTP is incorporated into the chain. Synthesis stops at this point because a ddNTP lacks a hydroxyl group at carbon 3 and hence cannot participate in a 3-to-5 phosphodiester linkage, a necessary requirement for chain elongation (Section 22.3). Thus the portion of the reaction mixture that contains ddATP will be a mixture of all possible lengths of DNA complementary strands that terminate in ddA. Similarly, all of the complementary strands in the portion that contains ddGTP will terminate in ddG, and so on (see Figure 22.31c). Identification of the reaction mixture components. The newly synthesized complementary DNA strands of the four portions of the reaction mixture are then subjected to gel electrophoresis. Smaller DNA fragments move more rapidly through the gel than do larger ones, which is the basis for the separation. Fluorescence from the four differently marked ddNTPs present in the complementary strands is the basis for identification; the labeling pattern observed indicates the sequence of bases. Figure 22.31d shows the gel separation of the complementary nucleotide strands for the 10-base DNA segment shown in Figure 22.31a.

O N C E P TS TO R E M E M B E R

Nucleic acids. Nucleic acids are polymeric molecules in which the

Transcription. Transcription is the process in which the genetic

repeating units are nucleotides. Cells contain two kinds of nucleic acids—deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). The major biochemical functions of DNA and RNA are, respectively, transfer of genetic information and synthesis of proteins (Section 22.1). Nucleotides. Nucleotides, the monomers of nucleic acid polymers, are molecules composed of a pentose sugar bonded to both a phosphate group and a nitrogen-containing heterocyclic base. The pentose sugar must be either ribose or deoxyribose. Five nitrogen-containing bases are found in nucleotides: adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U) (Section 22.2). Primary nucleic acid structure. The “backbone” of a nucleic acid molecule is a constant alternating sequence of sugar and phosphate groups. Each sugar unit has a nitrogen-containing base attached to it (Section 22.3). Complementary bases. Complementary bases are specific pairs of bases in nucleic acid structures that hydrogen-bond to each other (Section 22.4). Secondary DNA structure. A DNA molecule exists as two polynucleotide chains coiled around each other in a double-helix arrangement. The double helix is held together by hydrogen bonding between complementary pairs of bases. Only two base-pairing combinations occur: A with T, and C with G (Section 22.4). DNA replication. DNA replication occurs when the two strands of a parent DNA double helix separate and act as templates for the synthesis of new chains using the principle of complementary base pairing (Section 22.5). Chromosome. A chromosome is a cell structure that consists of an individual DNA molecule bound to a group of proteins (Section 22.5). RNA molecules. Five important types of RNA molecules, distinguished by their function, are ribosomal RNA (rRNA), messenger RNA (mRNA), heterogeneous nuclear RNA (hnRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA) (Section 22.7).

information encoded in the base sequence of DNA is copied into hnRNA/mRNA molecules (Section 22.8). Gene. A gene is a portion of a DNA molecule that contains the base

sequences needed for the production of a specific hnRNA/mRNA molecule. Genes are segmented, with portions called exons that contain genetic information and portions called introns that do not convey genetic information (Section 22.8). Codon. A codon is a three-nucleotide sequence in mRNA that codes

for a specific amino acid needed during the process of protein synthesis (Section 22.9). Genetic code. The genetic code consists of all the mRNA codons that specify either a particular amino acid or the termination of protein synthesis (Section 22.9). Anticodon. An anticodon is a three-nucleotide sequence in tRNA

that binds to a complementary sequence (a codon) in mRNA (Section 22.10). Translation. Translation is the stage of protein synthesis in which the

codons in mRNA are translated into amino acid sequences of new proteins. Translation involves interactions between the codons of mRNA and the anticodons of tRNA (Section 22.11). Mutations. Mutations are changes in the base sequence in DNA molecules (Section 22.12). Recombinant DNA. Recombinant DNA molecules are synthesized

by splicing a segment of DNA, usually a gene, from one organism into the DNA of another organism (Section 22.14). Polymerase chain reaction. The polymerase chain reaction is a

method for rapidly producing many copies of a DNA sequence (Section 22.15). DNA sequencing. DNA sequencing is a multistep process for determining the sequence of bases in a DNA segment (Section 22.16).

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Chapter 22 Nucleic Acids

EY R E A C T I O N S A N D E Q U AT I O N S

1. Formation of a nucleotide (Section 22.2) Pentose sugar (ribose or deoxyribose)  phosphate ion  nitrogen-containing heterocyclic base ¡ Phosphate

Sugar Base

2. Formation of a nucleic acid (Section 22.3) Many deoxyribose-containing nucleotides ¡ DNA Many ribose-containing nucleotides ¡ RNA 3. Protein synthesis (Section 22.6)

 2H2O

Transcription

Translation

DNA 88888888n RNA 8888888n protein

EXERCISES a n d P R O B L E M S The members of each pair of problems in this section test similar material. Types of Nucleic Acids (Section 22.1)

22.18 Which nitrogen-containing base is present in each of the

22.1 What does the designation DNA stand for? 22.2 What does the designation RNA stand for? 22.3 What is the primary function within cells for RNA? 22.4 What is the primary function within cells for DNA? 22.5 Within human cells, where is the DNA located? 22.6 Within human cells, where is the RNA located? 22.7 What is the general name for the building blocks (monomers)

following nucleotides? a. GMP b. dAMP

c. CMP

22.19 Which pentose sugar is present in each of the nucleotides in

Problem 22.17?

22.20 Which pentose sugar is present in each of the nucleotides in

Problem 22.18?

22.21 Characterize as true or false each of the following statements

about the given nucleotide.

from which an RNA molecule is made? 22.8 What is the general name for the building blocks (monomers) from which a DNA molecule is made? Nucleotides (Section 22.2) 22.9 How many subunits are present within a nucleotide? 22.10 What are the name of the subunits present within a nucleotide?

d. dCMP

O CH3

N



O A O P P OOO CH2 A O

O

N

O

H

22.11 What is the structural difference between the pentose sugars

ribose and 2-deoxyribose? 22.12 What are the names of the pentose sugars present, respectively, in DNA and RNA molecules? 22.13 Characterize each of the following nitrogen-containing bases as

a purine derivative or a pyrimidine derivative. a. Thymine b. Cytosine c. Adenine d. Guanine 22.14 Characterize each of the following nitrogen-containing bases as a component of (1) both DNA and RNA, (2) DNA but not RNA, or (3) RNA but not DNA. a. Adenine b. Thymine c. Uracil d. Cytosine 22.15 How many different choices are there for each of the following

subunits in the specified type of nucleotide? a. Pentose sugar subunit in DNA nucleotides b. Nitrogen-containing base subunit in RNA nucleotides c. Phosphate subunit in DNA nucleotides 22.16 How many different choices are there for each of the following subunits in the specified type of nucleotide? a. Pentose sugar subunit in RNA nucleotides b. Nitrogen-containing base subunit in DNA nucleotides c. Phosphate subunit in RNA nucleotides 22.17 Which nitrogen-containing base is present in each of the

following nucleotides? a. AMP b. dGMP

c. dTMP

d. UMP

OH

H

a. The nitrogen-containing base is a purine derivative. b. The phosphate group is attached to the sugar unit at carbon 3. c. The sugar unit is ribose. d. The nucleotide could be a component of both DNA and RNA. 22.22 Characterize as true or false each of the following statements about the given nucleotide.

O O A O P P OOO CH2 A O

N O

N

N N

H NH2

OH OH a. The sugar unit is 2-deoxyribose. b. The sugar unit is attached to the nitrogen-containing base at nitrogen 3. c. The nitrogen-containing base is a pyrimidine derivative. d. The nucleotide could be a component of both DNA and RNA. 22.23 Draw the structures of the three products produced when the

nucleotide in Problem 22.21 undergoes hydrolysis.

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Exercises and Problems

22.24 Draw the structures of the three products produced when the

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22.27 What distinguishes various DNA molecules from each other?

ends labeled, for each of the following DNA base sequences. a. 5 ACGTAT 3 b. 5 TTACCG 3 c. 3 GCATAA 5 d. AACTGG 22.46 Using the concept of complementary base pairing, write the complementary DNA strands, with their 5 and 3 ends labeled, for each of the following DNA base sequences. a. 5 CCGGTA 3 b. 5 CACAGA 3 c. 3 TTTAGA 5 d. CATTAC

22.28 What distinguishes various RNA molecules from each other?

22.47 How many total hydrogen bonds would exist between the DNA

nucleotide in Problem 22.22 undergoes hydrolysis.

Primary Nucleic Acid Structure (Section 22.3) 22.25 What are the two repeating subunits present in the backbone portion of a nucleic acid? 22.26 To which type of subunit in a nucleic acid backbone are the nitrogen-containing bases attached?

22.29 What is the difference between a nucleic acid’s 3 end and its 5

end? 22.30 In the lengthening of a polynucleotide chain, which type of nucleotide subunit would bond to the 3 end of the polynucleotide chain? 22.31 What are the nucleotide subunits that participate in a nucleic

acid 3,5-phosphodiester linkage?

22.32 How many 3,5-phosphodiester linkages are present in a tetra-

nucleotide segment of a nucleic acid?

22.33 Draw the structure of the dinucleotide product obtained by com-

bining the nucleotides of Problems 22.21 and 22.22 such that the Problem 22.21 nucleotide is the 5 end of the dinucleotide. 22.34 Draw the structure of the dinucleotide product obtained by combining the nucleotides of Problems 22.21 and 22.22 such that the Problem 22.21 nucleotide is the 3 end of the dinucleotide. The DNA Double Helix (Section 22.4) 22.35 Describe the DNA double helix in terms of a. general shape. b. what is on the outside of the helix and what is within the interior of the helix. 22.36 Describe the DNA double helix in terms of a. the directionality of the two polynucleotide chains present. b. a comparison of the total number of nitrogen-containing bases present in each of the two polynucleotide chains. 22.37 The base content of a particular DNA molecule is 36% thy-

mine. What is the percentage of each of the following bases in the molecule? a. Adenine b. Guanine c. Cytosine 22.38 The base content of a particular DNA molecule is 24% guanine. What is the percentage of each of the following bases in the molecule? a. Adenine b. Cytosine c. Thymine

strand 5 AGTCCTCA 3 and its complementary strand? 22.48 How many total hydrogen bonds would exist between the DNA strand 5 CCTAGGAT 3 and its complementary strand? Replication of DNA Molecules (Section 22.5) 22.49 What is the function of the enzyme DNA helicase in the DNA replication process? 22.50 What are two functions of the enzyme DNA polymerase in the DNA replication process? 22.51 In the replication of a DNA molecule, two daughter molecules,

Q and R, are formed. The following base sequence is part of the newly formed strand in daughter molecule Q. 5 ACTTAG 3

Indicate the corresponding base sequence in a. the newly formed strand in daughter molecule R. b. the “parent” strand in daughter molecule Q. c. the “parent” strand in daughter molecule R. 22.52 In the replication of a DNA molecule, two daughter molecules, S and T, are formed. The following base sequence is part of the “parent” strand in daughter molecule S. 5 TTCAGAG 3 Indicate the corresponding base sequence in a. the newly formed strand in daughter molecule T. b. the newly formed strand in daughter molecule S. c. the “parent” strand in daughter molecule T. 22.53 During DNA replication, one of the newly formed strands

grows continuously, whereas the other grows in segments that are later connected together. Explain why this is so. 22.54 DNA replication is most often a bidirectional process. Explain why this is so. 22.55 What is a chromosome?

22.39 In terms of hydrogen bonding, a G–C base pair is more stable

22.56 Chromosomes are nucleoproteins. Explain.

22.41 What is the relationship between the total number of purine

Overview of Protein Synthesis (Section 22.6) 22.57 What type of molecule is the starting material for the transcription phase of protein synthesis? 22.58 What type of molecule is the end product for the transcription phase of protein synthesis?

than an A–T base pair. Explain why this is so. 22.40 What structural consideration prevents the following bases from forming complementary base pairs? a. A and G b. T and C bases (A and G) and the total number of pyrimidine bases (C and T) present in a DNA double helix? 22.42 The base composition for one of the strands of a DNA double helix is 19% A, 34% C, 28% G, and 19% T. What is the percent base composition for the other strand of the DNA double helix? 22.43 Identify the 3 and 5 ends of the DNA base sequence TAGCC.

22.59 What type of molecule is the starting material for the translation

phase of protein synthesis? 22.60 What type of molecule is the end product for the translation phase of protein synthesis? RNA Molecules (Section 22.7)

22.44 The two-base DNA sequences TA and AT represent different di-

22.61 What are the four major differences between RNA molecules

22.45 Using the concept of complementary base pairing, write

22.62 What are the names and abbreviations for the five major types

nucleotides. Explain why this is so.

the complementary DNA strands, with their 5 and 3

and DNA molecules? of RNA molecules?

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Chapter 22 Nucleic Acids

22.63 State whether each of the following phrases applies to hnRNA,

mRNA, tRNA, rRNA, or snRNA. a. Material from which messenger RNA is made b. Delivers amino acids to protein synthesis sites c. Smallest of the RNAs in terms of nucleotide units present d. Also goes by the designation ptRNA 22.64 State whether each of the following phrases applies to hnRNA, mRNA, tRNA, rRNA, or snRNA. a. Associated with a series of proteins in a complex structure b. Contains genetic information needed for protein synthesis c. Most abundant type of RNA in a cell d. Involved in the editing of hnRNA molecules 22.65 For each of the following types of RNA, indicate whether the

22.81 In the process of splicing, which type of RNA

a. undergoes the splicing? b. is present in the spliceosomes? 22.82 What is the difference between snRNA and snRNPs? 22.83 What is alternative splicing? 22.84 How many different mRNAs can be produced from an

hnRNA that contains three exons, one of which is an “alternative” exon?

The Genetic Code (Section 22.9) 22.85 What is a codon? 22.86 On what type of RNA molecule are codons found?

predominant cellular location for the RNA is the nuclear region, the extranuclear region, or both the nuclear and the extranuclear regions. a. hnRNA b. tRNA c. rRNA d. mRNA 22.66 Indicate whether each of the following processes occurs in the nuclear or the extranuclear region of a cell. a. DNA transcription b. Processing of hnRNA to mRNA c. mRNA translation (protein synthesis) d. DNA replication

22.87 Using the information in Table 22.2, determine what amino

Transcription: RNA Synthesis (Section 22.8) 22.67 What serves as a template in the process of transcription? 22.68 What is the initial product of the transcription process?

22.91 Explain why the base sequence ATC could not be a codon.

22.69 What are two functions of the enzyme RNA polymerase in the

22.93 Predict the sequence of amino acids coded by the mRNA

transcription process? 22.70 What is a gene?

interactions? 22.72 In DNA–DNA interactions there are two complementary base pairs, and in DNA–RNA interactions there are three complementary base pairs. Explain. 22.73 Write the base sequence of the hnRNA formed by transcrip-

tion of the following DNA base sequence. 5 ATGCTTA 3

22.74 Write the base sequence of the hnRNA formed by transcrip-

tion of the following DNA base sequence. 5 TAGTGAT 3

22.75 From what DNA base sequence was the following hnRNA

sequence transcribed?

5 UUCGCAG 3 22.76 From what DNA base sequence was the following hnRNA sequence transcribed? 5 GCUUAUC 3 22.77 What is the relationship between an exon and a gene? 22.78 What is the relationship between an intron and a gene? 22.79 What mRNA base sequence would be obtained from the fol-

lowing portion of a gene?

intron

exon

5 TCAG–TAGC–TTCA 3 22.80 What mRNA base sequence would be obtained from the fol-

lowing portion of a gene? intron

22.89 Using the information in Table 22.2, determine the

synonyms, if any, of each of the codons in Problem 22.87.

22.90 Using the information in Table 22.2, determine the

synonyms, if any, of each of the codons in Problem 22.88.

22.92 Explain why the base sequence AGAC could not be a

codon.

sequence

22.71 What are the complementary base pairs in DNA–RNA

exon

acid is coded for by each of the following codons. a. CUU b. AAU c. AGU d. GGG 22.88 Using the information in Table 22.2, determine what amino acid is coded for by each of the following codons. a. GUA b. CCC c. CAC d. CCA

exon

intron

5 TTAC–AACG–GCAT 3

5 AUG–AAA–GAA–GAC–CUA 3 22.94 Predict the sequence of amino acids coded by the mRNA

sequence

5 GGA–GGC–ACA–UGG–GAA 3 Anticodons and tRNA Molecules (Section 22.10) 22.95 Describe the general structure of a tRNA molecule. 22.96 Where is the anticodon site on a tRNA molecule? 22.97 By what type of bond is an amino acid attached to a tRNA

molecule?

22.98 What principle governs the codon–anticodon interaction

that leads to proper placement of amino acids in proteins?

22.99 What is the anticodon that would interact with each of the

following codons? a. AGA b. CGU c. UUU d. CAA 22.100 What is the anticodon that would interact with each of the following codons? a. CCU b. GUA c. AUC d. GCA 22.101 Which amino acid will a tRNA molecule be carrying if its

anticodon is the following? a. CCC b. CAG c. UGC d. GAG 22.102 Which amino acid will a tRNA molecule be carrying if its anticodon is the following? a. GGG b. GAC c. AUA d. CGA 22.103 What are the possible codons that a tRNA molecule could

react with if it is carrying each of the following amino acids? (Note that a given tRNA will be specific for one or more of the possible codons.) a. Serine b. Leucine c. Isoleucine d. Glycine

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Exercises and Problems

22.104 What are the possible codons that a tRNA molecule could in-

teract with if it is carrying each of the following amino acids? (Note that a given tRNA will be specific for one or more of the possible codons.) a. Valine b. Cysteine c. Alanine d. Tyrosine

Translation: Protein Synthesis (Section 22.11) 22.105 What is a ribosome? 22.106 Approximately how many ribosomes are present in cells of higher organisms? 22.107 What is the chemical composition of a ribosome’s active site? 22.108 To which subunit of a ribosome does mRNA bind? 22.109 What are the two steps involved in the activation of a tRNA

molecule?

22.110 Why is the first amino acid in a developing human protein

always the amino acid Met?

22.111 In the elongation phase of translation, at which site in the

ribosome does new peptide bond formation actually take place? 22.112 What two changes occur at a ribosome during protein synthesis immediately after peptide bond formation? 22.113 What types of events occur during post-translation processing

of a protein? 22.114 At what stage of protein formation does folding of the protein into its active conformation occur? 22.115 Write a possible mRNA base sequence that would lead to the

production of this pentapeptide. (There is more than one correct answer.) Gly–Ala–Cys–Val–Tyr 22.116 Write a possible mRNA base sequence that would lead to the production of this pentapeptide. (There is more than one correct answer.) Lys–Met–Thr–His–Phe Mutations (Section 22.12) 22.117 For the codon sequence 5⬘ GGC–UAU–AGU–AGC–CCC 3⬘ write the amino acid sequence produced in each of the following ways. a. Translation proceeds in a normal manner. b. A mutation changes CCC to CCU. c. A mutation changes CCC to ACC. 22.118 For the codon sequence 5⬘ GGA–AUA–UGG–UUC–CUA 3⬘ write the amino acid sequence produced in each of the following ways. a. Translation proceeds in a normal manner. b. A mutation changes GGA to GGG. c. A mutation changes GGA to CGA. Viruses and Vaccines (Section 22.13) 22.119 Describe the general structure of a virus. 22.120 What is the only function of a virus? 22.121 What is the most common method by which viruses invade cells? 22.122 Why must a virus infect another organism in order to

reproduce?

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Recombinant DNA and Genetic Engineering (Section 22.14) 22.123 How does recombinant DNA differ from normal DNA? 22.124 Give two reasons why bacterial cells are used for recombinant

DNA procedures.

22.125 What role do plasmids play in recombinant DNA

procedures?

22.126 Describe what occurs when a particular restriction enzyme

operates on a segment of double-stranded DNA.

22.127 Describe what happens during transformation. 22.128 How are plasmids obtained from E. coli bacteria? 22.129 A particular restriction enzyme will cleave DNA between A

and A in the sequence AAGCTT in the 5⬘-to-3⬘ direction. Draw a diagram showing the structural details of the “sticky ends” that result from cleavage of the following DNA segment. 5¿ 3¿ C C A A G C T T G G G T T C G A A C 3¿ 5¿

22.130 A particular restriction enzyme will cleave DNA between A

and A in the sequence AAGCTT in the 5⬘-to-3⬘ direction. Draw a diagram showing the structural details of the “sticky ends” that result from cleavage of the following DNA segment. 5¿ 3¿ G G A A G C T T A C C T T C G A A T 3¿ 5¿

Polymerase Chain Reaction (Section 22.15) 22.131 What is the function of the polymerase chain reaction? 22.132 What is the function of the enzyme DNA polymerase in the

PCR process?

22.133 What is a primer and what is its function in the PCR process? 22.134 What are the four types of substances needed to carry out the

PCR process?

DNA Sequencing (Section 22.16) 22.135 How do the notations dATP and ddATP differ in meaning? 22.136 What role do dideoxynucleotides play in the DNA sequencing process? 22.137 Assume that the red lines in the first and second columns of

Figure 22.31d are interchanged, while the other labels stay the same. a. Given this change, what would be the sequence of bases in the DNA fragment under study? b. Given this change, what would be the sequence of bases in the original DNA fragment that was to be sequenced? 22.138 Assume that the “red lines” in the second and fourth columns of Figure 22.31d are interchanged, while the other labels stay the same. a. Given this change, what would be the sequence of bases in the DNA fragment under study? b. Given this change, what would be the sequence of bases in the original DNA fragment that was to be sequenced?

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Chapter 22 Nucleic Acids

ADDITIONAL PROBLEMS 22.139 With the help of the structures given in Section 22.2, describe

the structural differences between the following pairs of nucleotide bases. a. Thymine and uracil b. Adenine and guanine 22.140 The following is a sequence of bases for an exon portion of a strand of a gene. 5 CATACAGCCTGGAAGCTC 3 a. What is the sequence of bases on the strand of DNA complementary to this segment? b. What is the sequence of bases on the mRNA molecule synthesized from this strand? c. What codons are present on the mRNA molecule from part b? d. What anticodons will be found on the tRNA molecules that interact with the codons from part c? e. What is the sequence of amino acids in the peptide formed using these protein synthesis instructions? 22.141 Which of these RNA types, (1) mRNA, (2) hnRNA, (3) rRNA, or (4) tRNA, is most closely associated with each of the following terms? a. Codon b. Anticodon c. Intron d. Amino acid carrier 22.142 Which of these processes, (1) translation phase of protein synthesis, (2) transcription phase of protein synthesis, (3) replication of DNA, or (4) formation of recombinant DNA, is associated with each of the following events? a. Complete unwinding of a DNA molecule occurs. b. Partial unwinding of a DNA molecule occurs. c. An mRNA–ribosome complex is formed. d. Okazaki fragments are formed.

22.143 Which of these base-pairing situations, (1) between two DNA

segments, (2) between two RNA segments, (3) between a DNA segment and an RNA segment, or (4) between a codon and an anticodon, fits each of the following base-pairing sequences? More than one response may apply to a given base-pairing situation. a. A G T b. A C T o o o o o o U CA T GA c. A G U d. C C G o o o o o o U CA GGC 22.144 Which of these characterizations, (1) found in DNA but not RNA, (2) found in RNA but not DNA, (3) found in both DNA and RNA, or (4) not found in DNA or RNA, fits each of the following mono-, di-, or trinucleotides? a. 5 dAMP–dAMP 3 b. 5 AMP–AMP–CMP 3 c. 5 dAMP–CMP 3 d. 5 GGA 3 22.145 Suppose that 28% of the nucleotides of a DNA molecule are deoxythymidine 5-monophosphate, and during replication the relative amounts of available nucleotide bases are 22% A, 28% T, 22% C, and 28% G. What base would be depleted first in the replication process? 22.146 On the basis of the most recent results of the Human Genome Project concerning the DNA present in a human cell a. How many base-pairs are present in the DNA? b. How many genes are present in the DNA? c. What percentage of the base-pairs are accounted for by the genes?

multiple-Choice Practice Test 22.147 Which of the following is not a structural subunit of a

22.148

22.149

22.150

22.151

nucleotide? a. A nitrogen-containing heterocyclic base b. A pentose sugar c. An amino acid d. A phosphate The number of kinds of RNA nucleotides is which of the following? a. The same as the number of kinds of DNA nucleotides b. Double the number of kinds of DNA nucleotides c. Less than the number of kinds of DNA nucleotides d. Greater than the number of kinds of DNA nucleotides In which of the following pairs of nucleotide bases are both members of the pair “single-ring” bases? a. A and C b. G and T c. T and U d. A and G Which of the following elements is not present in the “backbone” of a nucleic acid molecule? a. Nitrogen b. Carbon c. Oxygen d. Hydrogen In a DNA double helix, the base pairs are which of the following? a. Part of the backbone structure b. Located inside the helix c. Located outside the helix d. Covalently bonded to each other

22.152 Which of the following types of RNA has a “cloverleaf

22.153

22.154

22.155

22.156

shape” with three hairpin loops? a. mRNA b. rRNA c. hnRNA d. tRNA Which of the following types of RNA contains introns and exons? a. hnRNA b. mRNA c. tRNA d. rRNA Which of the following events occurs during the translation phase of protein synthesis? a. mRNA is converted to hnRNA. b. tRNAs carry amino acids to the site for protein synthesis. c. A partial unwinding of a DNA double helix occurs. d. tRNAs interact with ribosomes. The genetic code is a listing that gives the relationships between which of the following? a. Codons and anticodons b. Codons and amino acids c. Anticodons and amino acids d. Codons and genes What is the complementary hnRNA sequence to the DNA sequence CTA–TAC? a. TCG–CGT b. GAU–AUG c. UGC–GCU d. TCG–CGT

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Biochemical Energy Production Chapter Outline 23.1 Metabolism 777 23.2 Metabolism and Cell Structure 779 23.3 Important Intermediate Compounds in Metabolic Pathways 781

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23.4 High-Energy Phosphate Compounds 786 23.5 An Overview of Biochemical Energy Production 788 23.6 The Citric Acid Cycle 788

CHEMISTRY AT A GLANCE: Simplified Summary of the Four Stages of Biochemical Energy Production 790 CHEMISTRY AT A GLANCE: Summary of the Reactions of the Citric Acid Cycle 794 23.7 The Electron Transport Chain 794

CHEMISTRY AT A GLANCE: Summary of the Flow of Electrons Through the Four Complexes of the Electron Transport Chain 799 23.8 Oxidative Phosphorylation 800

CHEMISTRY AT A GLANCE: Summary of the Common Metabolic Pathway 802 23.9 ATP Production for the Common Metabolic Pathway 802 23.10 The Importance of ATP 804 23.11 Non-ETC Oxygen-Consuming Reactions 804

The energy consumed by these scarlet ibises in flight is generated by numerous sequences of biochemical reactions that occur within their bodies.

T

his chapter is the first of four dealing with the chemical reactions that occur in a living organism. In this first chapter, we consider those molecules that are repeatedly encountered in biological reactions, as well as those reactions that are common to the processing of carbohydrates, lipids, and proteins. The three following chapters consider the reactions associated uniquely with carbohydrate, lipid, and protein processing, respectively.

23.1 METABOLISM

CHEMICAL CONNECTIONS Cyanide Poisoning 801 Brown Fat, Newborn Babies, and Hibernating Animals 803 Flavonoids: An Important Class of Dietary Antioxidants 805

Catabolism is pronounced ca-TABo-lism, and anabolism is pronounced an-ABB-o-lism. Catabolic is pronounced CAT-a-bol-ic, and anabolic is pronounced AN-a-bol-ic.

Metabolism is the sum total of all the biochemical reactions that take place in a living organism. Human metabolism is quite remarkable. An average human adult whose weight remains the same for 40 years processes about 6 tons of solid food and 10,000 gallons of water, during which time the composition of the body is essentially constant. Just as we must put gasoline in a car to make it go or plug in a kitchen appliance to make it run, we also need a source of energy to think, breathe, exercise, or work. As we have seen in previous chapters, even the simplest living cell is continually carrying on energy-demanding processes such as protein synthesis, DNA replication, RNA transcription, and membrane transport. Metabolic reactions fall into one of two subtypes: catabolism and anabolism. Catabolism is all metabolic reactions in which large biochemical molecules are broken down to smaller ones. Catabolic reactions usually release energy. The reactions involved in the oxidation of glucose are catabolic. Anabolism is all metabolic reactions in which small biochemical molecules are joined together to form larger ones. Anabolic reactions usually require energy in order to proceed. The synthesis of proteins

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Chapter 23 Biochemical Energy Production

Figure 23.1 The processes of catabolism and anabolism are opposite in nature. The first usually produces energy, and the second usually consumes energy.

Catabolism

Smaller molecules

Larger molecules + Energy

A n a b o li s m

from amino acids is an anabolic process. Figure 23.1 contrasts catabolic and anabolic processes. The metabolic reactions that occur in a cell are usually organized into sequences called metabolic pathways. A metabolic pathway is a series of consecutive biochemical reactions used to convert a starting material into an end product. Such pathways may be linear, in which a series of reactions generates a final product, or cyclic, in which a series of reactions regenerates the first reactant. Enzyme 1

Linear metabolic pathway:

A

Cyclic metabolic pathway:

A

B

D

C

B

Enzyme 2

C

Enzyme 3

D

The major metabolic pathways for all life forms are similar. This enables scientists to study metabolic reactions in simpler life forms and use the results to help understand the corresponding metabolic reactions in more complex organisms, including humans.

EXAMPLE 23.1 Distinguishing Between Anabolic and Catabolic Processes

Classify each of the following chemical processes as anabolic or catabolic. a. b. c. d.

Synthesis of a polysaccharide from monosaccharides Hydrolysis of a pentasaccharide to monosaccharides Formation of a nucleotide from phosphate, nitrogenous base, and pentose sugar Hydrolysis of a triacylglycerol to glycerol and fatty acids

Solution

a. b. c. d.

Anabolic. A large molecule is formed from many small molecules. Catabolic. Five monosaccharides are produced from a larger molecule. Anabolic. Three subunits are combined to give a larger unit. Catabolic. A four-subunit molecule is broken down into four smaller molecules.

Practice Exercise 23.1 Classify each of the following chemical processes as anabolic or catabolic. a. b. c. d.

Synthesis of a protein from amino acids Formation of a triacylglycerol from glycerol and fatty acids Hydrolysis of a polysaccharide to monosaccharides Formation of a nucleic acid from nucleotides

Answers: a. Anabolic; b. Anabolic; c. Catabolic; d. Anabolic

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23.2 Metabolism and Cell Structure

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23.2 METABOLISM AND CELL STRUCTURE

The term eukaryotic, pronounced you-KAHR-ee-ah-tic, is from the Greek eu, meaning “true,” and karyon, meaning “nucleus.” The term prokaryotic, which contains the Greek pro, meaning “before,” literally means “before the nucleus.”

Eukaryotic and prokaryotic cells differ in that the former contain a well-defined nucleus, set off from the rest of the cell by a membrane.

B

F

A protective mechanism exists to prevent lysosome enzymes from destroying the cell in which they are found if they should be accidently released (via membrane rupture or leakage). The optimum pH (Section 21.6) for lysosome enzyme activity is 4.8. The cytoplasmic pH of 7.0–7.3 renders them inactive.

Mitochondria, pronounced my-toeKON-dree-ah, is plural. The singular form of the term is mitochondrion. The threadlike shape of the inner membrane of the mitochondria is responsible for this organelle’s name; mitos is Greek for “thread,” and chondrion is Greek for “granule.”

Knowledge of the major structural features of a cell is a prerequisite to understanding where metabolic reactions take place. Cells are of two types: prokaryotic and eukaryotic. Prokaryotic cells have no nucleus and are found only in bacteria. The DNA that governs the reproduction of prokaryotic cells is usually a single circular molecule found near the center of the cell in a region called the nucleoid. A eukaryotic cell is a cell in which the DNA is found in a membraneenclosed nucleus. Cells of this type, which are found in all higher organisms, are about 1000 times larger than bacterial cells. Our focus in the remainder of this section will be on eukaryotic cells, the type present in humans. Figure 23.2 shows the general internal structure of a eukaryotic cell. Note the key components shown: the outer membrane, nucleus, cytosol, ribosomes, lysosomes, and mitochondria. The cytoplasm is the water-based material of a eukaryotic cell that lies between the nucleus and the outer membrane of the cell. Within the cytoplasm are several kinds of small structures called organelles. An organelle is a minute structure within the cytoplasm of a cell that carries out a specific cellular function. The organelles are surrounded by the cytosol. The cytosol is the water-based fluid part of the cytoplasm of a cell. Three important types of organelles are ribosomes, lysosomes, and mitochondria. We have considered ribosomes before; they are the sites where protein synthesis occurs (Section 22.11). A lysosome is an organelle that contains hydrolytic enzymes needed for cellular rebuilding, repair, and degradation. Some lysosome enzymes hydrolyze proteins to amino acids; others hydrolyze polysaccharides to monosaccharides. Bacteria and viruses “trapped” by the body’s immune system (Section 20.16) are degraded and destroyed by enzymes from lysosomes. A mitochondrion is an organelle that is responsible for the generation of most of the energy for a cell. Much of the discussion of this chapter deals with the energyproducing chemical reactions that occur within mitochondria. Further details of mitochondrion structure will help us understand more about how these reactions occur. Mitochondria are sausage-shaped organelles containing both an outer membrane and a multifolded inner membrane (see Figure 23.3). The outer membrane, which is about 50% lipid and 50% protein, is freely permeable to small molecules. The inner membrane, which is about 20% lipid and 80% protein, is highly impermeable to most substances. The nonpermeable nature of the inner membrane divides a mitochondrion into two separate compartments—an interior region called the matrix and the region between the

Figure 23.2 A schematic representation of a eukaryotic cell with selected internal components identified.

Lysosome Plasma membrane

Cytosol Mitochondria

Nucleus

Ribosomes (small dots)

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Chapter 23 Biochemical Energy Production

Outer membrane Inner membrane

Matrix

Cristae Intermembrane space

ATP synthase complex (a)

(b)

Figure 23.3 (a) A schematic representation of a mitochondrion, showing key features of its internal structure. (b) An electron micrograph showing the ATP synthase knobs extending into the matrix.

inner and outer membranes, called the intermembrane space. The folds of the inner membrane that protrude into the matrix are called cristae. The invention of high-resolution electron microscopes allowed researchers to see the interior structure of the mitochondrion more clearly and led to the discovery, in 1962, of small spherical knobs attached to the cristae called ATP synthase complexes. As their name implies, these relatively small knobs, which are located on the matrix side of the inner membrane, are responsible for ATP synthesis, and their association with the inner membrane is critically important for this task. More will be said about ATP in the next section.

EXAMPLE 23.2 Recognizing Structural Characteristics of a Mitochondrion

Identify each of the following structural features of a mitochondrion. a. b. c. d.

The more permeable of the two mitochondrial membranes The mitochondrial membrane that has cristae The mitochondrial membrane that determines the size of the matrix The mitochondrial membrane that is interior to the intermembrane space

Solution

a. Outer membrane. The outer membrane is more permeable. b. Inner membrane. Cristae are “folds” present on the inner membrane. c. Inner membrane. The matrix is the center part of a mitochondrion and is surrounded by the inner membrane. d. Inner membrane. The intermembrane space separates the outer membrane from the inner membrane.

Practice Exercise 23.2 Identify each of the following structural features of a mitochondrion. a. b. c. d.

The mitochondrial membrane that is highly folded. The mitochondrial membrane with the higher protein content. The mitochondrial membrane that is exterior to the intermembrane space. The mitochondrial membrane with which ATP synthase complexes are associated.

Answers: a. Inner membrane; b. Inner membrane; c. Outer membrane; d. Inner membrane

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23.3 Important Intermediate Compounds in Metabolic Pathways

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23.3 IMPORTANT INTERMEDIATE COMPOUNDS IN METABOLIC PATHWAYS Nucleotides, besides being the monomer units from which nucleic acids are made, are also present in several nonpolymeric molecules that are important in energy production in living things.

As a prelude to an overview presentation (Section 23.5) of the metabolic processes by which our food is converted to energy, we now consider several compounds that repeatedly function as key intermediates in these metabolic pathways. Knowing about these compounds will make it easier to understand the details of metabolic pathways. The compounds to be discussed all have nucleotides (Section 22.2) as part of their structures.

Adenosine Phosphates (ATP, ADP, and AMP) Several adenosine phosphates exist. Of importance in metabolism are adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP). AMP is not a new molecule to us; it is one of the nucleotides present in RNA molecules (Section 22.2). ADP and ATP differ structurally from AMP only in the number of phosphate groups present. Block structural diagrams for these three adenosine phosphates follow. Phosphate Ribose Adenine AMP Phosphate Phosphate Ribose Adenine ADP Phosphate Phosphate Phosphate Ribose Adenine ATP

Figure 23.4 shows actual structural formulas for these three adenosine phospates. In ATP, a phosphoester bond joins the first phosphoryl group to the pentose sugar ribose. The other two phosporyl groups are joined to one another by phosphoanhydride bonds, as shown in the figure. A phosphoryl group is the functional group derived from a phosphate ion that is part of another molecule. ATP contains three phosphoryl groups, ADP two phosphoryl groups, and AMP one phosphoryl group. When two phosphate groups react with one another, a water molecule is produced (Section 16.20); hence the use of the word anhydride in describing the chemical bonds present between phosphoryl groups in ATP and ADP. A phosphoanhydride bond is the chemical bond formed when two phosphate groups react with each other and a water molecule is produced. ATP and ADP molecules readily undergo hydrolysis reactions in which phosphate groups (Pi, inorganic phosphate) are released ATP  H2O 88n ADP  Pi  energy ADP  H2O 88n AMP  Pi  energy ATP  2H2O 88n AMP  2Pi  energy

Figure 23.4 Structures of the various phosphate forms of adenosine.

Phosphoanhydride bonds O –

O

P O–

O O

P O–

Phosphoester bond

N

O O

P

NH2 N

O

N

Adenine

N Adenosine

CH2 O

O–

Ribose OH OH

Adenosine monophosphate (AMP) Adenosine diphosphate (ADP) Adenosine triphosphate (ATP)

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In metabolic pathways in which they are involved, the adenosine phosphates continually change back and forth among the various forms: ATP Δ ADP Δ AMP

These hydrolyses are energy-producing reactions that are used to drive cellular processes that require energy input. The phosphoanhydride bonds in ATP and ADP are very reactive bonds that require less energy than normal to break. The presence of such reactive bonds, which are often called strained bonds (see Section 23.4), is the basis for the net energy production that accompanies hydrolysis. Greater-than-normal electron–electron repulsive forces at specific locations within a molecule are the cause for bond strain; in ATP and ADP, it is the highly electronegative oxygen atoms in the additional phosphate groups that cause the increased repulsive strain. A typical cellular reaction in which ATP functions as both a source of a phosphate group and a source of energy is the conversion of glucose to glucose-6-phosphate, a reaction that is the first step in the process of glycolysis (Section 24.2). H A H O OOCOH A A HO

OH A

H A P OOOCOH A

O A  ATP OH

Hexokinase

ADP 

A HO

Glucose

A OH

OH A

A OH

O The symbol P is a shorthand notation for a PO32– unit.

A OH

Glucose 6-phosphate

ATP is not the only nucleotide triphosphate present in cells, although it is the most prevalent. The other nitrogen-containing bases associated with nucleotides (Section 22.2) are also present in triphosphate form. Uridine triphosphate (UTP) is involved in carbohydrate metabolism, guanosine triphosphate (GTP) participates in protein and carbohydrate metabolism, and cytidine triphosphate (CTP) is involved in lipid metabolism.

Flavin Adenine Dinucleotide (FAD, FADH2) Flavin adenine dinucleotide (FAD) is a coenzyme (Section 21.2) required in numerous metabolic redox reactions. Structurally, FAD can be visualized as containing either three subunits or six subunits. A block diagram of FAD from the three-subunit viewpoint is Flavin

Ribitol

ADP

Flavin and ribitol, the two components attached to the ADP unit, together constitute the B vitamin riboflavin (Section 21.12). The block diagram for FAD from the six-subunit viewpoint is Flavin

Ribitol

Phosphate

Adenine

Ribose

Phosphate

This block diagram shows the basis for the name flavin adenine dinucleotide. Ribitol is a reduced form of ribose; a 9CH2OH group is present in place of the 9CHO group (Section 18.12).

H H H

CHO OH OH OH CH2OH D-Ribose

H H H

CH2OH OH OH OH CH2OH D-Ribitol

The complete structural formula of FAD is given in Figure 23.5a. The active portion of FAD in metabolic redox reactions is the flavin subunit of the molecule. The flavin is reduced, converting the FAD to FADH2, a molecule with two additional hydrogen atoms. Thus FAD is the oxidized form of the molecule, and FADH2 is the reduced form. Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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23.3 Important Intermediate Compounds in Metabolic Pathways

O C NH2

CH3 CH3

N H

N C

N O

N

OH OH OH H C

C

C

C

H H H H H

O O

P

O

O–

N H

N

O P

O

Adenine

O

N

Ribose

CH2

CH2 O

OH OH

O–

O –

O

P

NH2

O

N

N

O –

O

ADP Flavin

Ribitol

Nicotinamide

N+

N

OH OH

O

NH2

Adenosine diphosphate (ADP)

N

P

O

O

CH2

Adenine

N

O

Riboflavin

OH OH

(b) Nicotinamide adenine dinucleotide (NAD+)

(a) Flavin adenine dinucleotide (FAD)

Figure 23.5 Structural formulas of the molecules flavin adenine dinucleotide, FAD (a) and nicotinamide adenine dinucleotide, NAD (b).

O H

N

N O

H

CH3

N



 2H  2e N

H

O

O

CH3

N

N

R

H

FAD (oxidized form)

R=

Ribitol

N

CH3

N

CH3

R FADH2 (reduced form)

ADP

A typical cellular reaction in which FAD serves as the oxidizing agent involves a 9CH29CH29 portion of a substrate being oxidized to produce a carbon–carbon double bond. In metabolic pathways in which it is involved, flavin adenine dinucleotide continually changes back and forth between its oxidized form and its reduced form. 2H  2e  FAD 34 FADH 2

R

H

H

C

C

H

R  FAD

H

R

CH

CH R  FADH2

Unsaturated (oxidized)

Saturated (reduced)

For an enzyme-catalyzed redox reaction involving removal of two hydrogen atoms, such as this, each removed hydrogen atom is equivalent to a hydrogen ion, H, plus an electron, e. 2 H atoms 1removed2 ¡ 2H 1 1 2e 2 On the basis of this equivalency, the summary equation relating the oxidized and reduced forms of flavin adenine dinucleotide is usually written as ⎧ ⎪ ⎨ ⎪ ⎩

2H  2e  FAD 34 FADH 2 2 H atoms

Nicotinamide Adenine Dinucleotide (NADⴙ, NADH) Several parallels exist between the characteristics of nicotinamide adenine dinucleotide (NAD) and those of FAD. Both have coenzyme functions in metabolic redox pathways, both have a B vitamin as a structural component, and both can be represented structurally by using a three-subunit or a six-subunit formulation. In the case of NAD, the B vitamin present is nicotinamide (Section 21.12). The three-subunit block diagram for the structure of NAD is Nicotinamide

Ribose

ADP

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The six-subunit block diagram, which emphasizes the dinucleotide nature of the coenzyme, as well as the origin of its name, is Nicotinamide

Ribose

Phosphate

Adenine

Ribose

Phosphate

Examination of the detailed structure of NAD (Figure 23.5b) reveals the basis for the positive electrical charge. The  sign refers to the positive charge on the nitrogen atom in the nicotinamide component of the structure; this nitrogen atom has four bonds instead of the usual three (Section 17.6). The active portion of NAD in metabolic redox reactions is the nicotinamide subunit of the molecule. The nicotinamide is reduced, converting the NAD to NADH, a molecule with one additional hydrogen atom and two additional electrons. Thus NAD is the oxidized form of the molecule, and NADH is the reduced form. H

O NH2

C +

+ H+ + 2e–

N

NH2

N

R

R

NAD+ (oxidized form)

NADH (reduced form)

R= In metabolic pathways, nicotinamide adenine dinucleotide continually changes back and forth between its oxidized form and its reduced form.

H O C

H

Ribose

ADP

A typical cellular reaction in which NAD serves as the oxidizing agent is the oxidation of a secondary alcohol to give a ketone. OH R

2H  2e  NAD  34 NADH  H

C

O R  NAD

H

R

C

R  NADH  H

Ketone

2 alcohol

In this reaction, one hydrogen atom of the alcohol substrate is directly transferred to NAD, whereas the other appears in solution as H ion. Both electrons lost by the alcohol go to the nicotinamide ring in NADH. (Two electrons are required, rather than one, because of the original positive charge on NAD.) Thus the summary equation relating the oxidized and reduced forms of nicotinamide adenine dinucleotide is written as ⎧ ⎪ ⎨ ⎪ ⎩

2H  2e  NAD  34 NADH  H 2 H atoms

Coenzyme A (CoA–SH) Another important coenzyme in metabolic pathways is coenzyme A, a derivative of the B vitamin pantothenic acid (Section 21.12). The three-subunit and six-subunit block diagrams for coenzyme A are 2-Aminoethanethiol

Pantothenic acid

Phosphorylated ADP

and 2-Aminoethanethiol

Pantothenic acid

Phosphate

Adenine

Phosphorylated ribose

Phosphate

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23.3 Important Intermediate Compounds in Metabolic Pathways

785 NH2

N

OH CH3 HS

CH2

CH2

NH

C O

CH2

CH2

NH

C O

C H

C

O CH2

O

P

O –

CH3

O

P O

O

CH2

N

O

N

–

4'

1' 3'

2'

2–

O3PO

2-Aminoethanethiol

N

O

Pantothenic acid

OH

Phosphorylated ADP

Figure 23.6 Structural formula for coenzyme A (CoA–SH).

In metabolic pathways, coenzyme A is continually changing back and forth between its CoA form and its acetyl CoA form. H S CoA O B CH3 C S CoA

Note, in the three-subunit block diagram, that the ADP subunit present is phosphorylated. As shown in Figure 23.6, the complete structural formula for coenzyme A, the phosphorylated version of ADP carries an extra phosphate group attached to carbon 3 of its ribose. The active portion of coenzyme A is the sulfhydryl group (9SH group; Section 14.20) in the ethanethiol subunit of the coenzyme. For this reason, the abbreviation CoA–SH is used for coenzyme A. Think of the letter A in the name coenzyme A as reflecting a general metabolic function of this substance; it is the transfer of acetyl groups in metabolic pathways. An acetyl group is the portion of an acetic acid molecule (CH3–COOH) that remains after the —OH group is removed from the carboxyl carbon atom. An acetyl group bonds to CoA–SH through a thioester bond (Section 16.17) to give acetyl CoA. Acetyl group

An acetyl group, which can be considered to be derived from acetic acid, has the structure O B CH3OCO

O B CH3OCOOH

Acetyl group

Acetic acid

Thioester bond O B CH3 OCO S O CoA Acetyl CoA

Classification of Metabolic Intermediate Compounds The metabolic intermediate compounds considered in this section can be classified into three groups based on function. The classifications are: 1. Intermediates for the storage of energy and transfer of phosphate groups 2. Intermediates for the transfer of electrons in metabolic redox reactions 3. Intermediates for the transfer of acetyl groups Figure 23.7 shows the category assignment for the intermediates previously considered.

Figure 23.7 Classification of metabolic intermediate compounds in terms of function.

Intermediates for the storage of energy and transfer of phosphate groups

ATP

ADP

Intermediates for the transfer of electrons in metabolic redox reactions

FAD

FADH2

NAD+

NADH

Intermediates for the transfer of acetyl groups

H–S–CoA

AMP

acetyl–S–CoA

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EXAMPLE 23.3 Recognizing Relationships Among Metabolic Intermediate Compounds

Give the abbreviated formula for the following metabolic intermediate compounds. a. b. c. d.

The intermediate produced when FAD is reduced The intermediate produced when FADH2 is oxidized The intermediate produced when ATP loses two phosphoryl groups as a PPi The intermediate produced when acetyl–S–CoA transfers an acetyl group

Solution

a. In FAD reduction two hydrogen ions and two electrons are acquired by the FAD to produce FADH2. b. In FADH2 oxidation two hydrogen ions and two electrons are released by the FADH2 to produce FAD. FADH2 oxidation and FAD reduction (part a) are reverse processes. c. Loss of one phosphoryl group by ATP as Pi produces ADP. Loss of two phosphoryl groups by ATP as PPi produces AMP. d. Release of the acetyl group from acetyl CoA (acetyl–S–CoA) produces coenzyme A (H–S–CoA) itself.

Practice Exercise 23.3 Give the abbreviated formula for the following metabolic intermediate compounds. a. b. c. d.

The intermediate produced when NADH is oxidized The intermediate produced when NAD is reduced The intermediate produced when a phosphate group is added to AMP The intermediate produced when CoA–S–H bonds to an acetyl group

Answers: a. NAD; b. NADH; c. ADP; d. Acetyl–S–CoA

23.4 HIGH-ENERGY PHOSPHATE COMPOUNDS

In the definition for a high-energy compound, the term free energy rather than simply energy was used. Free energy is the amount of energy released by a chemical reaction that is actually available for further use at a given temperature and pressure. In reality, the energy released in a chemical reaction is divisible into two parts. One part, lost as heat, is not available for further use. The other part, the free energy, is available for further use; in cells, it can be used to “drive” reactions that require energy.

B

F

In a chemical reaction, the energy balance between bond breaking among reactants (energy input) and new bond formation among products (energy release) determines whether there is a net loss or a net gain of energy (Section 9.5).

In the previous section, we noted that knowing about several key intermediate compounds in metabolic reactions makes it easier to understand the yet-to-come details of metabolic processes. In like manner, knowing about a particular type of bond present in certain phosphate-containing metabolic intermediates makes the details of metabolic processes easier to understand. Several phosphate-containing compounds found in metabolic pathways are known as high-energy compounds. A high-energy compound is a compound that has a greater free energy of hydrolysis than that of a typical compound. High-energy compounds differ from other compounds in that they contain one or more very reactive bonds, often called strained bonds. The energy required to break these strained bonds during hydrolysis is less than that generally required to break a chemical bond. Consequently, the balance between the energy needed to break bonds in the reactants and that released by bond formation in the products is such that more than the typical amount of free energy is released during the hydrolysis reaction. Greater-than-normal electron–electron repulsive forces at specific locations within a molecule are the cause of bond strain. Highly electronegative atoms and/or highly charged atoms occurring together in a molecule cause increased repulsive forces and thus increase bond strain. Let us specifically consider bond strain as it is related to phosphate-containing organic molecules involved in metabolic pathways. The parent molecule for phosphate groups is phosphoric acid, H3PO4, a weak triprotic inorganic acid (Section 10.4). This acid exists in aqueous solution in several forms, the dominant form at cellular pH being HPO42 ion. O B HOO P OO A O

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23.4 High-Energy Phosphate Compounds

The designation high-energy compound does not mean that a compound is different from other compounds in terms of bonding. High-energy compounds obey the normal rules for chemical bonding. The only difference between such compounds and other compounds is the presence of one or more strained bonds. The breaking of such bonds requires lower-thannormal amounts of energy.

O O B B HOO P OOO P OO A A O O

787

O O O B B B HOO P OOO P OOO P OO A A A O O O

Note the presence in these three phosphate structures of highly electronegative oxygen atoms, many of which bear negative charges. The factors that can produce bond strain are present when phosphates (mono-, di-, and tri-) are bonded to certain organic molecules. Table 23.1 gives the structures of commonly encountered phosphate-containing compounds, as well as a numerical parameter—the free energy of hydrolysis—that can be considered a measure of the extent of bond strain in the molecules. The more negative the free energy of

TABLE 23.1 Free Energies of Hydrolysis of Common Phosphate-Containing Metabolic Compounds

Free Energy of Hydrolysis (kcal/mole)

Type

Example

enol phosphates

phosphoenolpyruvate

14.8

1,3-bisphosphoglycerate acetyl phosphate

11.8 11.3

creatine phosphate arginine phosphate

10.3 9.1

O B R O ⬃ P OO G D A  C O B C D G H H acyl phosphates

O B O O ⬃ P OO M D A C O A R guanidine phosphates

NOH O B B RONO C ON ⬃ P OO A A A H H O The —PO32 group as part of a larger organic phosphate molecule is referred to as a phosphoryl group.

triphosphates

O O O B B B ROOO P OO ⬃ P OO ⬃ P OO A A A O O O diphosphates

O O B B ROOO P OO ⬃ P OO A A O O sugar phosphates

O B ROOO P OO A O

ATP ¡ AMP  PPi* ATP ¡ ADP  Pi*

7.7 7.5

PPi ¡ 2Pi ADP ¡ AMP  Pi

7.8 7.5

glucose 1-phosphate fructose 6-phosphate AMP ¡ adenosine  Pi glucose 6-phosphate glycerol 3-phosphate

5.0 3.8 3.4 3.3 2.2

*The notation Pi is used as a general designation for any free monophosphate species present in cellular fluid. Free diphosphate ions are designated as PPi (“i” stands for inorganic).

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Chapter 23 Biochemical Energy Production

hydrolysis, the greater the bond strain. A free-energy release greater than 6.0 kcal/mole is generally considered indicative of bond strain. In Table 23.1, strained bonds within the molecules are noted with a squiggle (~), a notation often employed to denote strained bonds.

23.5 AN OVERVIEW OF BIOCHEMICAL ENERGY PRODUCTION The energy needed to run the human body is obtained from ingested food through a multistep process that involves several different catabolic pathways. There are four general stages in the biochemical energy production process, and numerous reactions are associated with each stage. The first stage of biochemical energy production, digestion, is not considered part of metabolism because it is extracellular. Metabolic processes are intracellular.

Stage 1: The first stage, digestion, begins in the mouth (saliva contains starch-digesting enzymes), continues in the stomach (gastric juices), and is completed in the small intestine (the majority of digestive enzymes and bile salts). The end products of digestion—glucose and other monosaccharides from carbohydrates, amino acids from proteins, and fatty acids and glycerol from fats and oils—are small enough to pass across intestinal membranes and into the blood, where they are transported to the body’s cells. Stage 2: The second stage, acetyl group formation, involves numerous reactions, some of which occur in the cytosol of cells and some in cellular mitochondria. The small molecules from digestion are further oxidized during this stage. Primary products include two-carbon acetyl units (which become attached to coenzyme A to give acetyl CoA) and the reduced coenzyme NADH. Stage 3: The third stage, the citric acid cycle, occurs inside mitochondria. Here acetyl groups are oxidized to produce CO2 and energy. Some of the energy released by these reactions is lost as heat, and some is carried by the reduced coenzymes NADH and FADH2 to the fourth stage. The CO2 that we exhale as part of the breathing process comes primarily from this stage. Stage 4: The fourth stage, the electron transport chain and oxidative phosphorylation, also occurs inside mitochondria. NADH and FADH2 supply the “fuel” (hydrogen ions and electrons) needed for the production of ATP molecules, the primary energy carriers in metabolic pathways. Molecular O2, inhaled via breathing, is converted to H2O in this stage. The reactions in stages 3 and 4 are the same for all types of foods (carbohydrates, fats, proteins). These reactions constitute the common metabolic pathway. The common metabolic pathway is the sum total of the biochemical reactions of the citric acid cycle, the electron transport chain, and oxidative phosphorylation. The remainder of this chapter deals with the common metabolic pathway. The reactions of stages 1 and 2 of biochemical energy production differ for different types of foodstuffs. They are discussed in Chapters 24–26, which cover the metabolism of carbohydrates, fats (lipids), and proteins, respectively. The Chemistry at a Glance feature on page 790 summarizes the four general stages in the process of production of biochemical energy from ingested food. This diagram is a very simplified version of the “energy generation” process that occurs in the human body, as will become clear from the discussions presented in later sections of this chapter, which give further details of the process.

23.6 THE CITRIC ACID CYCLE Figure 23.8 Hans Adolf Krebs (1900–1981), a German-born British biochemist, received the 1953 Nobel Prize in medicine for establishing the relationships among the different compounds in the cycle that carries his name, the Krebs cycle.

The citric acid cycle is the series of biochemical reactions in which the acetyl portion of acetyl CoA is oxidized to carbon dioxide and the reduced coenzymes FADH2 and NADH are produced. This cycle, stage 3 of biochemical energy production, gets its name from the first intermediate product in the cycle, citric acid. It is also known as the Krebs cycle, after its discoverer Hans Adolf Krebs (see Figure 23.8), and as the tricarboxylic acid cycle, in reference to the three carboxylate groups present in citric acid. Figure 23.9 lists the compounds produced in all eight steps of the citric acid cycle.

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23.6 The Citric Acid Cycle

Figure 23.9 The citric acid cycle. Details of the numbered steps are given in the text.

789

Acetyl CoA C2 Starting point

Oxaloacetate C4

1

2

Oxidation

8

Citrate C6

Condensation

Isomerization Isocitrate C6

Malate C4

7

Hydration

3

Oxidation and decarboxylation

Fumarate C4

␣-Ketoglutarate C5 6

Oxidation 4

Succinate C4

5

Oxidation and decarboxylation

Phosphorylation Succinyl CoA C4

B

F

The chemical reactions of the citric acid cycle take place in the mitochondrial matrix where the needed enzymes are found, except the succinate dehydrogenase reaction that involves FAD. The enzyme that catalyzes this reaction is an integral part of the inner mitochondrial membrane. We shall now consider the individual steps of the cycle in detail. As we go through these steps, we will observe two important types of reactions: (1) oxidation, which produces NADH and FADH2, and (2) decarboxylation, wherein a carbon chain is shortened by the removal of a carbon atom as CO2.

The formation of citryl CoA involves addition of acetyl CoA to the carbon–oxygen double bond. A hydrogen atom of the acetyl —CH3 group adds to the oxygen atom of the double bond, and the remainder of the acetyl CoA adds to the carbon atom of the double bond (Section 15.10).

Reactions of the Citric Acid Cycle Step 1: Formation of Citrate. Acetyl CoA, which carries the two-carbon degradation product of carbohydrates, fats, and proteins (Section 23.5), enters the cycle by combining with the four-carbon keto dicarboxylate species oxaloacetate. This results in the transfer of the acetyl group from coenzyme A to oxaloacetate, producing the C6 citrate species and free coenzyme A.

At cellular pH, citric acid is actually present as citrate ion. Despite this, the name of the cycle is the citric acid cycle, which references the molecular, rather than ionic, form of the substance.

O B OPC O COO  CO SOCoA A A CH2 CH3 A COO 

Oxaloacetate

Acetyl CoA

Citrate synthase

O B CO S OCoA A CH2 A HOO CO COO A CH2 A COO Citryl CoA

Citrate synthase

H2O

COO A CH2 A HOO CO COO  CoAO SH  H A CH2 A COO Citrate

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Chapter 23 Biochemical Energy Production

Simplified Summary of the Four Stages of Biochemical Energy Production Ingested Food

STAGE 1

Fats

The process of digestion changes large, complex molecules into relatively small, simpler ones. Fatty acids

STAGE 2 Small molecules from digestion are degraded to still smaller units, primarily the two-carbon acetyl group that becomes part of acetyl CoA.

Glycerol

Carbohydrates

Proteins

Glucose and other sugars

Amino acids

Acetyl Group Formation (acetyl CoA) CoA

SH

STAGE 3 Acetyl CoA is oxidized to produce CO2 and reduced coenzymes (NADH, FADH2) in the citric acid cycle.

CO2

CITRIC ACID CYCLE

CO2

STAGE 4 NADH and FADH2 facilitate ATP production through the electron transport chain and oxidative phosphorylation.

NADH, FADH2

O2

Electron transport chain and oxidative phosphorylation

ATP

A synthase is an enzyme that makes a new covalent bond during a reaction without the direct involvement of an ATP molecule.

Common Metabolic Pathway

ATP

H2O

ATP

There are two parts to the reaction: (1) the condensation of acetyl CoA and oxaloacetate to form citryl CoA, a process catalyzed by the enzyme citrate synthase, and (2) hydrolysis of the thioester bond in citryl CoA to produce CoA—SH and citrate, also catalyzed by the enzyme citrate synthase. Step 2: Formation of Isocitrate. Citrate is converted to its less symmetrical isomer isocitrate in an isomerization process that involves a dehydration followed by a hydration, both catalyzed by the enzyme aconitase. The net result of these reactions is that the —OH group from citrate is moved to a different carbon atom.

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23.6 The Citric Acid Cycle

B

F

COO A CH2 A HOO CO COO A HOCOH A COO

All acids found in the citric acid cycle exist as carboxylate ions (Section 16.8) at cellular pH.

H2O Aconitase

1. The hydroxyl group of isocitrate is oxidized to a ketone group. 2. NAD is converted to its reduced form, NADH. 3. A carboxyl group from the original oxaloacetate is removed as CO2.

The key happenings in Step 4 are the following: 1. A second NAD is converted to its reduced form, NADH. 2. A second carboxyl group is removed as CO2. 3. Coenzyme A reacts with the decarboxylation product succinate to produce succinyl CoA, a compound with a high-energy thioester bond. This is the second involvement of a coenzyme A molecule in the cycle, the other instance occurring in Step 1.

B

F

The thioester bond in succinyl CoA is a strained bond. Its hydrolysis releases energy, which is trapped by GTP formation. The function of the GTP produced is similar to that of ATP: to store energy in the form of a high-energy phosphate bond (Section 23.4).

Aconitase

Isocitrate

Citrate is a tertiary alcohol and isocitrate a secondary alcohol. Tertiary alcohols are not readily oxidized; secondary alcohols are easier to oxidize (Section 14.9). The next step in the cycle involves oxidation. Step 3: Oxidation of Isocitrate and Formation of CO2. This step involves oxidation– reduction (the first of four redox reactions in the citric acid cycle) and decarboxylation. The reactants are a NAD molecule and isocitrate. The reaction, catalyzed by isocitrate dehydrogenase, is complex: (1) Isocitrate is oxidized to a ketone (oxalosuccinate) by NAD, releasing two hydrogens. (2) One hydrogen and two electrons are transferred to NAD to form NADH; the remaining hydrogen ion (H) is released. (3) The oxalosuccinate remains bound to the enzyme and undergoes decarboxylation (loses CO2), which produces the C5 a-ketoglutarate (a keto dicarboxylate species). COO A CH2 A HO CO COO A H OO COH A COO

The CO2 molecules produced in Steps 3 and 4 of the citric acid cycle are the CO2 molecules we exhale in the process of respiration.

H2O

COO A CH2 A HO COCOO A HOO COH A COO

cis-Aconitate

Citrate

The key happenings in Step 3 are the following:

COO A CH2 A CO COO B COH A COO

791

NAD NAD H  H Isocitrate dehydrogenase

Isocitrate

COO A CH2 A HOCO COO A C PO A COO

H

Oxalosuccinate

CO2

COO A CH2 A HO COH A C PO A COO -Ketoglutarate

This step yields the first molecules of CO2 and NADH in the cycle. Step 4: Oxidation of a-Ketoglutarate and Formation of CO2. This second redox reaction of the cycle involves one molecule each of NAD, CoA—SH, and a-ketoglutarate. The catalyst is an aggregate of three enzymes called the a-ketoglutarate dehydrogenase complex. As in Step 3, both oxidation and decarboxylation occur. There are three products: CO2, NADH, and the C4 species succinyl CoA. COO A CH2 A CH2 A C PO A COO

 NAD  H  CoAO SH

-Ketoglutarate dehydrogenase complex

 -Ketoglutarate

COO A CH2 A CH2  NADH  CO2  H A C PO A S O CoA Succinyl CoA

Step 5: Thioester bond cleavage in Succinyl CoA and Phosphorylation of GDP. Two molecules react with succinyl CoA—a molecule of GDP (similar to ADP; Section 23.3) and a free phosphate group (Pi). The enzyme succinyl CoA synthetase removes coenzyme A by thioester bond cleavage. The energy released is used to combine GDP and Pi to form GTP. Succinyl CoA has been converted to succinate. COO A CH2 A CH2  GDP  Pi A C PO A S OCoA Succinyl CoA

Succinyl CoA synthetase

COO A CH2  GTP  CoAO SH A CH2 A COO Succinate

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Chapter 23 Biochemical Energy Production

Steps 6 through 8 of the citric acid cycle involve a sequence of functional group changes that we have encountered several times in the organic sections of the text. The reaction sequence is

Alkane Step 6:

Fumarate, with its trans double bond, is an essential metabolic intermediate in both plants and animals. Its isomer, with a cis double bond, is called maleate, and it is toxic and irritating to tissues. Succinate dehydrogenase produces only the trans isomer of this unsaturated diacid.

1 Oxidation (dehydrogenation)

alkene

2 Hydration

3 Oxidation (dehydrogenation)

ketone

Oxidation of Succinate. This is the third redox reaction of the cycle. The enzyme involved is succinate dehydrogenase, and the oxidizing agent is FAD rather than NAD. Two hydrogen atoms are removed from the succinate to produce fumarate, a C4 species with a trans double bond. FAD is reduced to FADH2 in the process. COO A CH2 A  FAD CH2 A COO

H Succinate dehydrogenase 

OOC

Succinate

Step 7:

secondary alcohol

G D C B C D G

COO  FADH2 H

Fumarate

Hydration of Fumarate. The enzyme fumarase catalyzes the addition of water to the double bond of fumarate. The enzyme is stereospecific, so only the L isomer of the product malate is produced. COO A C OH  H2O B HO C A COO

Fumarase

Fumarate

COO A HOO COH A H O CO H A COO L-Malate

Step 8: Oxidation of L-Malate to Regenerate Oxaloacetate. In the fourth oxidation– reduction reaction of the cycle, a molecule of NAD reacts with malate, picking up two hydrogen atoms with their associated energy to form NADH  H. The product of this reaction is oxaloacetate, so we are back where we started. The oxaloacetate formed in this step can combine with another molecule of acetyl CoA (Step 1), and the cycle can begin again. COO A H OO COH  NAD A CH2 A COO

Malate dehydrogenase

L-Malate

COO A CP O  NAD H  H A CH2 A COO Oxaloacetate

Summary of the Citric Acid Cycle An overall summary equation for the citric acid cycle is obtained by adding together the individual reactions of the cycle: Acetyl CoA  3NAD   FAD  GDP  Pi  2H2O ¡ 2CO2  CoA¬SH  3NADH  2H  FADH 2  GTP Important features of the cycle include the following: 1. The “fuel” for the cycle is acetyl CoA, obtained from the breakdown of carbohydrates, fats, and proteins. 2. Four of the cycle reactions involve oxidation and reduction. The oxidizing agent is either NAD (three times) or FAD (once). The operation of the cycle depends on the availability of these oxidizing agents. Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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23.6 The Citric Acid Cycle

B

F

The eight B vitamins and their structures were discussed in Section 21.12.

793

3. In redox reactions, NAD is the oxidizing agent when a carbon–oxygen double bond is formed; FAD is the oxidizing agent when a carbon–carbon double bond is formed. 4. The three NADH and one FADH2 that are formed during the cycle carry electrons and H to the electron transport chain (Section 23.7) through which ATP is synthesized. 5. Two carbon atoms enter the cycle as the acetyl unit of acetyl CoA, and two carbon atoms leave the cycle as two molecules of CO2. The carbon atoms that enter and leave are not the same ones. The carbon atoms that leave during one turn of the cycle are carbon atoms that entered during the previous turn of the cycle. 6. Four B vitamins are necessary for the proper functioning of the cycle: riboflavin (in both FAD and the a-ketoglutarate dehydrogenase complex), nicotinamide (in NAD), pantothenic acid (in CoA—SH), and thiamine (in the a-ketoglutarate dehydrogenase complex). 7. One high-energy GTP molecule is produced by phosphorylation. The Chemistry at a Glance feature on page 794 gives a detailed diagrammatic summary of the reactions that occur in the citric acid cycle.

EXAMPLE 23.4 Recognizing the Reactants and Products of Various Steps in the Citric Acid Cycle

When one acetyl CoA is processed through the citric acid cycle, how many times does each of the following events occur? a. b. c. d.

A secondary alcohol group is oxidized to a ketone group. A NADH molecule is produced. A decarboxylation reaction occurs. A C6 molecule is produced.

Solution

a. Two. Both isocitrate (Step 3) and malate (Step 8) are secondary alcohols that are oxidized by NAD to ketones. b. Three. The product of the use of NAD as an oxidizing agent is NADH. Oxidation using NAD occurs in Steps 3, 4, and 8. c. Two. In Step 3 isocitrate is decarboxylated and in Step 4 a-ketoglutarate is decarboxylated. In each case the product is a CO2 molecule. d. Two. Citrate and isocitrate are C6 molecules. Citrate is produced in Step 1 and isocitrate is produced in Step 2.

Practice Exercise 23.4 When one acetyl CoA is processed through the citric acid cycle, how many times does each of the following events occur? a. b. c. d.

A FAD molecule is a reactant. A CoA–S–H molecule is produced. A dehydrogenase enzyme is needed for the reaction to occur. A C5 molecule is produced.

Answers: a. One (Step 6); b. Two (Steps 1 and 5); c. Four (Steps 3, 4, 6, and 8);

d. One (Step 3)

Regulation of the Citric Acid Cycle The rate at which the citric acid cycle operates is controlled by the body’s need for energy (ATP). When the body’s ATP supply is high, the ATP present inhibits the activity of citrate synthase, the enzyme in Step 1 of the cycle. When energy is being used at a high rate, a state of low ATP and high ADP concentrations, the ADP activates citrate synthase and the cycle speeds up. A similar control mechanism exists at Step 3, which involves isocitrate dehydrogenase; here NADH acts as an inhibitor and ADP as an activator.

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Chapter 23 Biochemical Energy Production

Summary of the Reactions of the Citric Acid Cycle CH3 CO

S CoA

Acetyl CoA C2 O

COO–

C

CH2 COO

H2O

–

NADH + H+

CH

CH2 COO–

HC OOC CH

COO–

1

Condensation

(hydroxy triacid)

Malate dehydrogenase

2

Oxidation

8

H2O

Aconitase

H2O

Isomerization

CH2 COO–

Malate C4

Isocitrate C6

(hydroxy diacid)

(hydroxy triacid)

H 2O

–

COO–

Citrate C6

Citrate synthase

(keto diacid)

NAD+

COO–

CH2 COO– HO C

CH2 COO–

Oxaloacetate C4

HO

H+ + CoA SH

7

Fumarase

3

H+ CO2

(unsaturated diacid)

␣-Keto-glutarate C5

Succinate dehydrogenase

FADH2

6

4 Succinate C4

CH2

COO–

5

Oxidation and decarboxylation

NAD+ NADH + H+ Succinyl CoA C4

GTP

COO–

CoA SH

Phosphorylation

CoA SH

CH2 O C

Succinyl CoA synthetase

(saturated diacid)

CH2 COO–

(keto diacid)

α-Ketoglutarate dehydrogenase complex

Oxidation

FAD

COO–

COO–

NADH + H+

Oxidation and decarboxylation

Fumarate C4

CH2

COO–

HO CH

NAD+

Isocitrate dehydrogenase

Hydration

CH

(thio diacid) GDP + Pi

CO2 CH2 COO– CH2 CO

S

CoA

23.7 THE ELECTRON TRANSPORT CHAIN The electron transport chain is also frequently called the respiratory chain.

The NADH and FADH2 produced in the citric acid cycle pass to the electron transport chain. The electron transport chain is a series of biochemical reactions in which electrons and hydrogen ions from NADH and FADH2 are passed to intermediate carriers and

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23.7 The Electron Transport Chain

795

then ultimately react with molecular oxygen to produce water. NADH and FADH2 are oxidized in this process. NADH  H ¡ NAD   2H  2e FADH 2 ¡ FAD  2H  2e The oxygen involved in the water formation associated with the electron transport chain is the oxygen we breathe.

Water is formed when the electrons and hydrogen ions that originate from these reactions react with molecular oxygen. O2 1 4e 2 1 4H 1 ¡ 2H2O The electrons that pass through the various steps of the electron transport chain (ETC) lose some energy with each transfer along the chain. Some of this “lost” energy is used to make ATP from ADP (oxidative phosphorylation), as we will see in Section 23.8. The enzymes and electron carriers needed for the ETC are located along the inner mitochondrial membrane. Within this membrane are four distinct protein complexes, each containing some of the molecules needed for the ETC process to occur. These four protein complexes, which are tightly bound to the membrane, are Complex I: NADH–coenzyme Q reductase Complex II: Succinate–coenzyme Q reductase Complex III: Coenzyme Q–cytochrome c reductase Complex IV: Cytochrome c oxidase Two electron carriers, coenzyme Q and cytochrome c, which are not tightly associated with any of the four complexes, serve as mobile electron carriers that shuttle electrons between the various complexes. Our discussion of the individual reactions that occur in the ETC is divided into four parts, each part dealing with the reactions associated with one of the four protein complexes.

Complex I: NADH–Coenzyme Q Reductase NADH, from the citric acid cycle, is the source for the electrons that are processed through complex I, the largest of the four protein complexes. Complex I contains over 40 subunits, including flavin mononucleotide (FMN) and several iron–sulfur proteins (FeSP). The net result of electron movement through complex I is the transfer of electrons from NADH to coenzyme Q (CoQ), a result implied by the name of complex I: NADH–coenzyme Q reductase. The actual electron transfer process is not, however, a single-step direct transfer of electrons from NADH to CoQ; several intermediate carriers are involved. The first electron transfer step that occurs in complex I involves the interaction of NADH with flavin mononucleotide (FMN). The NADH is oxidized to NAD (which can again participate in the citric acid cycle) as it passes two hydrogen ions and two electrons to FMN, which is reduced to FMNH2. NADH  H The FMN/FMNH2 pair is the third biochemical situation we have encountered in which a flavin molecule is present. The other two are the FAD/FADH2 pair and the B vitamin riboflavin. FMN differs from FAD in not having an adenine nucleotide. Both FMN and FAD are synthesized within the body from riboflavin.

Oxidation

2H  2e  FMN

NAD  2H  2e Reduction

FMNH2

NADH supplies both electrons and one of the H ions that are transferred; the other H  ion comes from the matrix solution. The actual changes that occur within the structure of FMN as it accepts the two electrons and two H ions are shown in Figure 23.10a. The next steps involve transfer of electrons from the reduced FMNH2 through a series of iron/sulfur proteins (FeSPs). The iron present in these FeSPs is Fe3, which is reduced to Fe2. The two H atoms of FMNH2 are released to solution as two H ions. Two FeSP molecules are needed to accommodate the two electrons released by FMNH2 because an Fe3/Fe2 reduction involves only one electron.

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Chapter 23 Biochemical Energy Production

Figure 23.10 Structural characteristics of the electron carriers flavin mononucleotide and coenzyme Q. (a) The oxidized form (FMN) and reduced form (FMNH2) of the electron carrier flavin mononucleotide. (b) The oxidized form (CoQ) and reduced form (CoQH2) of the electron carrier coenzyme Q.

O H3C

N

N

N

H3C

H

N

O

H3C

N

H3C

N

N

R

H

N

+ 2H+ + 2e– O

R R =

Ribitol

O

Phosphate

FMN (oxidized form)

FMNH2 (reduced form) (a)

O

OH CH3

CH3O

CH3O CH3

CH3O

(CH2

CH

C

CH3 CH3

+ 2H+ + 2e– CH2)10

CH3O

H

O

(CH2

CH

C

CH2)10

H

OH

CoQ (oxidized form)

CoQH2 (reduced form) (b)

FMNH2

Oxidation

2e  2Fe(III)SP

FMN  2H  2e Reduction

2Fe(II)SP

In the final complex I reaction, Fe(II)SP is reconverted into Fe(III)SP as each of two Fe(II)SP units passes an electron to CoQ, changing it from its oxidized form (CoQ) to its reduced form (CoQH2). 2Fe(II)SP

Oxidation

2e  2H  CoQ

B

F

The molecule quinone, a cyclic ketone (Section 15.3), has the structure. O

O

2Fe(III)SP  2e Reduction

CoQH2

Coenzyme Q, in both its oxidized and reduced forms, is lipid soluble and can move laterally within the mitochondrial membrane. Its function is to shuttle its newly acquired electrons to complex III, where it becomes the initial substrate for reactions at this complex. The Q in the designation coenzyme Q comes from the molecule quinone. Structurally, coenzyme Q is a quinone derivative. In its most common form, coenzyme Q has a long carbon chain containing 10 isoprene units (Section 13.6) attached to its quinone unit. The actual changes that occur within the structure of CoQ as it accepts the two electrons and the two H ions involve the quinone part of its structure, as is shown in Figure 23.10b. The two H ions that CoQ picks up in forming CoQH2 come from solution.

Complex II: Succinate–Coenzyme Q Reductase Complex II, which is much smaller than complex I, contains only 4 subunits, including two FeSPs. This complex is used to process the FADH2 that is generated in the citric acid cycle when succinate is converted to fumarate. (Thus the use of the term succinate in the name of complex II.) CoQ is associated with the operations in complex II in a manner similar to its actions in complex I. It is the final recipient of the electrons from FADH2, with iron–sulfur proteins serving as intermediaries. Thus complexes I and II produce a common product, the reduced form of coenzyme Q (CoQH2). As was the case with complex I, the reduced CoQH2 shuttles electrons to complex III.

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23.7 The Electron Transport Chain

NAD+ Citric acid cycle

797

CoQH2 Complex I Electron movement

NADH /H+

CoQ Complex III

FAD

CoQ

Citric acid cycle

Complex II Electron movement FADH2

CoQH2 (a)

Complex I NAD+

NADH /H+

Complex II

FMNH2

2Fe(III)SP

CoQH2

FMN

2Fe(II)SP

CoQ

FAD

2Fe(III)SP

CoQH2

FADH2

2Fe(II)SP

CoQ

Several FeSP steps

Several FeSP steps (b)

Figure 23.11 An overview of electron movement through complexes I and II of the electron transport chain. (a) CoQH2 carries electrons from both complexes I and II to complex III. (b) NADH is the substrate for complex I and FADH2 is the substrate for complex II. CoQH2 is the common product from both electron transfer processes.

FADH2

Oxidation

FAD  2H  2e

2e  2Fe(III)SP 2Fe(II)SP

Reduction

Oxidation

2e  2H  CoQ

2Fe(II)SP

2Fe(III)SP  2e Reduction

CoQH2

Figure 23.11 summarizes the electron transport chain reactions associated with complexes I and II. In Figure 23.11a the net process is shown with only starting and end products shown. In Figure 23.11b individual reaction detail is shown. Note the general pattern that is developing for the electron carriers. They are reduced in one step (accept electrons) and then regenerated (oxidized; lose electrons) in the next step so that they can again participate in electron transport chain reactions.

Complex III: Coenzyme Q–Cytochrome c Reductase 

All H ions required for the reactions of NADH, CoQ, and O2 in the ETC come from the matrix side of the inner mitochondrial membrane.

Complex III contains 11 different subunits. Electron carriers present include several iron–sulfur proteins as well as several cytochromes. A cytochrome is a hemecontaining protein in which reversible oxidation and reduction of an iron atom occur. Heme, a compound also present in hemoglobin and myoglobin (Section 20.13), has the structure

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Chapter 23 Biochemical Energy Production

CH3 In cytochromes the iron of the heme is involved in redox reactions in which the iron changes back and forth between the 2 and 3 oxidation states.

In cytochromes the heme present is bound to protein in such a way as to prevent the heme from combining with oxygen as it does when it is present in hemoglobin.

Iron/sulfur protein (FeSP) is a nonheme iron protein. Most proteins of this type contain sulfur, as is the case with FeSP. Often the iron is bound to the sulfur atom in the amino acid cysteine.

A feature that all steps in the ETC share is that as each electron carrier passes electrons along the chain, it becomes reoxidized and thus able to accept more electrons.

CHP CH2

N

H2CPCH

CH3

NO Fe O N H3C

CH2 O CH2 OCOOH

N

CH3

CH2 O CH2 OCOOH

Heme-containing proteins function similarly to FeSP; iron changes back and forth between the 3 and 2 oxidation states. Various cytochromes, abbreviated cyt a, cyt b, cyt c, and so on, differ from each other in (1) their protein constituents, (2) the manner in which the heme is bound to the protein, and (3) attachments to the heme ring. Again, because the Fe3/Fe2 system involves only a one-electron change, two cytochrome molecules are needed to move two electrons along the chain. The initial substrate for complex III is CoQH2 molecules carrying the electrons that have been processed through complex I (from NADH) and also those processed through complex II (from FADH2). The electron transfer process proceeds from CoQH2 to an FeSP, then to cyt b, then to another FeSP, then to cyt c1, and finally to cyt c. Cyt c can move laterally in the intermembrane space; it delivers its electrons to complex IV. Cyt c is the only one of the cytochromes that is water soluble. The initial oxidation–reduction reaction at complex III is between CoQH2 and an iron–sulfur protein (FeSP). CoQH2

CoQ  2e  2H

Oxidation

2e  2Fe(III)SP

Reduction

2Fe(II)SP

The H ions produced from the oxidation of CoQH2 go into cellular solution. All further redox reactions at complex III involve only electrons, which are conveyed further down the enzyme complex chain. Figure 23.12 shows diagrammatically the electron transfer steps associated with complex III.

Complex IV: Cytochrome c Oxidase Complex IV contains 13 subunits, including two cytochromes. The electron movement flows from cyt c (carrying electrons from complex III) to cyt a to cyt a3. In the final step of electron transfer, the electrons from cyt a3 and hydrogen ions from cellular solution combine with oxygen (O2) to form water. O2 1 4H 1 1 4e 2 ¡ 2H2O It is estimated that 95% of the oxygen used by cells serves as the final electron acceptor for the ETC.

Figure 23.12 Electron movement through complex III is initiated by the electron carrier CoQH2. In several steps the electrons are passed to cyt c.

Complex III CoQH2

2H+ + CoQ

3+

2Fe

2Fe2+

2Fe3+

2Fe2+

FeSP

cyt b

FeSP

cyt c1

2Fe2+

2Fe3+

2Fe2+

2Fe3+

2Fe3+ cyt c 2Fe2+

Copyright 2010 Cengage Learning, Inc. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.

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23.7 The Electron Transport Chain

799

Summary of the Flow of Electrons Through the Four Complexes of the Electron Transport Chain Intermembrane space

Inner mitochondrial membrane

Complex I

Complex II

Complex III

Complex IV

CoQ FeSP

FeSP FeSP FMN

FeSP

Cyt c

Cyt b

Cyt a

FeSP

Cyt a3

Cyt c1

Matrix NADH/H+ NAD+

FADH2

FAD

O2

H2O

Flow of electrons

Both hydrogen and electrons from NADH and FADH2 participate in the reactions involving enzyme complexes I and II. Following the formation of CoQH2, hydrogen ions no longer directly participate in enzyme complex reactions, that is, they are

not passed further down the enzyme complex chain. Instead they become part of the cellular solution, where they participate in several reactions including the process by which ATP is synthesized (Section 23.8).

The two cytochromes present in cytochrome c oxidase (a and a3) differ from previously encountered cytochromes in that each has a copper atom associated with it in addition to its iron center. The copper atom sites participate in the electron transfer process as do the iron atom sites, with the copper atoms going back and forth between the reduced Cu state and the oxidized Cu2 state. Figure 23.13 shows the electron transfer sequence through these copper and iron sites. The Chemistry at a Glance feature above is a schematic diagram summarizing the flow of electrons through the four complexes of the electron transport chain.

Figure 23.13 The electron transfer pathway through complex IV (cytochrome c oxidase). Electrons pass through both copper and iron centers and in the last step interact with molecular O2. Reduction of one O2 molecule requires the passage of four electrons through complex IV, one at a time.

Complex IV Cytochrome c oxidase 4e–

e– e– Fe Cyt c

Fe Fe

CuA

2H2O

CuB

e–

Cyt a

Cyt a3

O2 + 4H+

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Chapter 23 Biochemical Energy Production

EXAMPLE 23.5 Recognizing Relationships Among Electron Carriers and Enzyme Complexes in the Electron Transport Chain

With which of the four complexes in the electron transport chain is each of the following events associated? (There may be more than one correct answer in a given situation.) a. b. c. d.

Iron–sulfur proteins (FeSPs) are needed as reactants. The mobile electron carrier CoQ serves as a “shuttle molecule.” Molecular O2 is needed as a reactant. FAD is a product.

Solution

a. Complexes I, II, and III. Iron sulfur proteins accept electrons from NADH (complex I), FADH2 (complex II), and CoQH2 (complex III). b. Complexes I, II, and III. CoQ functions as a shuttle molecule between complex I and complex III and also between complex II and complex III. c. Complex IV. The final electron acceptor in the ETC is molecular O2. It combines with electrons and H ions to produce H2O. d. Complex II. FADH2 is converted to FAD at complex II.

Practice Exercise 23.5 With which of the four complexes in the electron transport chains is each of the following events associated? (There may be more than one correct answer in a given situation.) a. b. c. d.

The metal iron is present in the form of Fe2 and Fe3 ions. FADH2 is needed as a reactant. The metal copper is present in the form of Cu and Cu2 ions. Cytochromes are needed as reactants.

Answers: a. Complexes I, II, III, and IV; b. Complex II; c. Complex IV;

d. Complexes III and IV

23.8 OXIDATIVE PHOSPHORYLATION

B

F

Oxidative phosphorylation is not the only process by which ATP is produced in cells. A second process, substrate phosphorylation (Section 24.2), can also be an ATP source. However, the amount of ATP produced by this second process is much less than that produced by oxidative phosphorylation.

Oxidative phosphorylation is the biochemical process by which ATP is synthesized from ADP as a result of the transfer of electrons and hydrogen ions from NADH or FADH2 to O2 through the electron carriers involved in the electron transport chain. Oxidative phosphorylation is conceptually simple but mechanistically complex. Learning the “details” of oxidative phosphorylation has been—and still is—one of the most challenging research areas in biochemistry. One concept central to the oxidative phosphorylation process is that of coupled reactions. Coupled reactions are pairs of biochemical reactions that occur concurrently in which energy released by one reaction is used in the other reaction. Oxidative phosphorylation and the oxidation reactions of the electron transport chain are coupled systems. The interdependence (coupling) of ATP synthesis with the reactions of the ETC is related to the movement of protons (H ions) across the inner mitochondrial membrane. Three of the four protein complexes involved in the ETC chain (I, III, and IV) have a second function besides electron transfer down the chain. They also serve as “proton pumps,” transferring protons from the matrix side of the inner mitochondrial membrane to the intermembrane space (Figure 23.14). Some of the H ions crossing the inner mitochondrial membrane come from the reduced electron carriers, and some come from the matrix; the details of how the H ions cross the inner mitochondrial membrane are not fully understood. For every two electrons passed through the ETC, four protons cross the inner mitochondrial membrane through complex I, four through complex III, and two more through complex IV. This proton flow causes a buildup of H ions (protons) in the

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23.8 Oxidative Phosphorylation

Figure 23.14 A second function for protein complexes I, III, and IV involved in the electron transport chain is that of proton pump. For every two electrons passed through the ETC, 10 H ions are transferred from the mitochondrial matrix to the intermembrane space through these complexes.

4H+

Intermembrane space

4H+

2H+

Complex III

Complex IV

801

Inner membrane Matrix Complex I

intermembrane space; this high concentration of protons becomes the basis for ATP synthesis (Figure 23.15). The “proton flow” explanation for ATP–ETC coupling is formally called chemiosmotic coupling. Chemiosmotic coupling is an explanation for the coupling of ATP synthesis with electron transport chain reactions that requires a proton gradient across the inner mitochondrial membrane. The main concepts in this explanation for coupling follow.

The difference in H ion concentration between the two sides of the inner mitochondrial membrane causes a pH difference of about 1.4 units. A pH difference of 1.4 units means that the intermembrane space, the more acidic region, has 25 times more protons than the matrix.

c

Complex II

1. The result of the pumping of protons from the mitochondrial matrix across the inner mitochondrial membrane is a higher concentration of protons in the intermembrane space than in the matrix. This concentration difference constitutes an electrochemical (proton) gradient. A chemical gradient exists whenever a substance has a higher concentration in one region than in another. Because the proton has an electrical

HEMICAL

Cyanide Poisoning

Inhalation of hydrogen cyanide gas (HCN) or ingestion of solid potassium cyanide (KCN) rapidly inhibits the electron transport chain in all tissues, making cyanide one of the most potent and rapidly acting poisons known. The attack point for the cyanide ion (CN) is cytochrome c oxidase, the last of the four protein complexes in the electron transport chain. Cyanide inactivates this complex by bonding itself to the Fe3 in the complex’s heme portions. As a result, Fe3 is unable to transfer electrons to oxygen, blocking the cell’s use of oxygen. Death results from

tissue asphyxiation, particularly of the central nervous system. Cyanide also binds to the heme group in hemoglobin, blocking oxygen transport in the bloodstream. One treatment for cyanide poisoning is to administer various nitrites, NO2, which oxidize the iron atoms of hemoglobin to Fe3. This form of hemoglobin helps draw CN back into the bloodstream, where it can be converted to thiocyanate (SCN) by thiosulfate (S2O32), which is administered along with the nitrite (see the accompanying figure).

Administered medications Bloodstream NO2– 2+

Hb(Fe )

S2O32– NO3–

Hb(Fe3+) – CN

SCN – Hb(Fe3+)

3+

Hb(Fe )

Tissues Cytochrome a3 – (Fe3+) – CN

Nonfunctional enzyme

CN –

onnections

Cytochrome a3 – (Fe3+)

Functional enzyme

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Chapter 23 Biochemical Energy Production

Summary of the Common Metabolic Pathway Acetyl CoA Complex I Complex II Complex III

Suc

rate

CO2

F0 H+ NADH/H+

H+ FADH2

Electron transport chain

F1

H+

O2 + 4H+ + 4e–

2H2O

ADP + Pi

ATP

oA

l-C ciny

cina

te

e

Suc

e itrat Isoc Citric acid CO2 cycle α-K etog luta rate

H+

Cyt c

CoQ

Cit

tate ace

lo Oxa

Oxidative phosphorylation

Ma late

arat Fum

Complex IV

O2

B

F

Some of the energy released at each of the protein complexes I, III, and IV is consumed in the movement of H ions across the inner membrane from the matrix into the intermembrane space. Movement of ions from a region of lower concentration (the matrix) to one of higher concentration (the intermembrane space) requires the expenditure of energy because it opposes the natural tendency, as exhibited in the process of osmosis (Section 8.9), to equalize concentrations.

H2O

ADP

ATP

charge (H ion), an electrical gradient also exists. Potential energy (Section 7.2) is always associated with an electrochemical gradient. 2. A spontaneous flow of protons from the region of high concentration to the region of low concentration occurs because of the electrochemical gradient. This proton flow is not through the membrane itself (it is not permeable to H ions) but rather through enzyme complexes called ATP synthases located on the inner mitochondrial membrane (Section 23.2). This proton flow through the ATP synthases “powers” the synthesis of ATP. ATP synthases are thus the coupling factors that link the processes of oxidative phosphorylation and the electron transport chain. 3. ATP synthase has two subunits, the F0 and F1 subunits (Figure 23.15). The F0 part of the synthase is the channel for proton flow, whereas the formation of ATP takes place in the F1 subunit. As protons return to the mitochondrial matrix through the F0 subunit, the potential energy associated with the electrochemical gradient is released and used in the F1 subunit for the synthesis of ATP. ATP synthase

ADP  Pi 888888888n ATP  H2O

B

F

Without oxygen, the biochemical systems of the human body quickly shut down and death occurs. Why? Without oxygen as the final electron acceptor in the ETC, the ETC chain shuts down and ATP production stops. Without ATP to power life’s processes (Chapters 24–26), these processes stop.

The Chemistry at a Glance feature above brings together into one diagram the three processes that constitute the common metabolic pathway: the citric acid cycle, the electron transport chain, and oxidative phosphorylation. These three processes operate together. Discussing them separately, as we have done, is a matter of convenience only.

23.9 ATP PRODUCTION FOR THE COMMON METABOLIC PATHWAY For each mole of NADH oxidized in the ETC, 2.5 moles of ATP are formed. FADH2, which does not enter the ETC at its start, produces only 1.5 moles of ATP per mole of FADH2 oxidized. FADH2’s entrance point into the chain, complex II, is beyond the first

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23.9 ATP Production for the Common Metabolic Pathway

803

Figure 23.15 Formation of ATP accompanies the flow of protons from the intermembrane space back into the mitochondrial matrix. The proton flow results from an electrochemical gradient across the inner mitochondrial membrane.

Outer mitochondrial membrane H+ +

+

H

H

H+

Intermembrane space +

H

H+

H+

H+

H+

H+ H

H+

H+

+

+

H

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

Inner mitochondrial membrane Matrix H+ H+

c

H H+

+

H+

H

H+

+

H

F0

H+

+

+

+

H H H Electron transport chain

H+ Decreased [H+]

+

Increased [H+] H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+ F 1

H+ ADP + Pi

ATP

“proton-pumping” site, complex I. Hence fewer ATP molecules are produced from FADH2 than from NADH. The energy yield, in terms of ATP production, can now be totaled for the common metabolic pathway (Section 23.5). Every acetyl CoA entering the citric acid cycle (CAC) produces three NADH, one FADH2, and one GTP (which is equivalent in energy

HEMICAL

onnections

Brown Fat, Newborn Babies, and Hibernating Animals

Ordinarily, metabolic processes generate enough heat to maintain normal body temperature. In certain cases, however, including newborn infants and hibernating animals, normal metabolism is not sufficient to meet the body’s heat requirements. In these cases, a supplemental method of heat generation, which involves brown fat tissue, occurs. Brown fat tissue, as the name implies, is darker in color than ordinary fat tissue, which is white. Brown fat is specialized for heat production. It contains many more blood vessels and mitochondria than white fat. (The increased number of mitochondria gives brown fat its color.) Another difference between the two types of fat is that the mitochondria in brown fat cells contain a protein called thermogenin, which functions as an uncoupling agent. This protein “uncouples” the ATP production associated with the electron transport chain. The ETC reactions still take place, but the energy that would ordinarily be used for ATP synthesis is simply released as heat. Brown fat tissue is of major importance for newborn infants. Newborns are immediately faced with a temperature regulation problem. They leave an environment of constant 37C temperature and enter a much colder environment (25C). A supply of active brown fat, present at birth, helps the baby adapt to the cooler environment. Very limited amounts of brown fat are present in most adults. However, stores of brown fat increase in adults who are regularly exposed to cold environs. Thus the production of

Hibernating bears rely on brown fat tissue to help meet their bodies’ heat requirements.

brown fat is one of the body’s mechanisms for adaptation to cold. Thermogenin, the uncoupling agent in brown fat, is a protein bound to the inner mitochondrial membrane. When activated, it functions as a proton channel through the inner membrane. The proton gradient produced by the electron transport chain is dissipated through this “new” proton channel, and less ATP synthesis occurs because the normal proton channel, ATP synthase, has been bypassed. The energy of the proton gradient, no longer useful for ATP synthesis, is released as heat.

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Chapter 23 Biochemical Energy Production

Figure 23.16 The interconversion of ADP + Pi

ATP and ADP is the principal medium for energy exchange in biochemical processes.

ATP

FOOD CATABOLISM

LIFE PROCESSES

Oxidation of Carbohydrates Fats Proteins

Cellular work Muscle contracting Nutrient transport Synthesis of essential compounds

ATP

Biochemistry textbooks published before the mid-1990s make the following statements: 1 NADH produces 3 ATP in the ETC. 1 FADH2 produces 2 ATP in the ETC. As more has been learned about the electron transport chain and oxidative phosphorylation, these numbers have had to be reduced. The overall conversion process is more complex than was originally thought, and not as much ATP is produced.

ADP + Pi

to ATP; Section 23.6). Thus 10 molecules of ATP are produced for each acetyl CoA catabolized. 3 NADH ¡ 7.5 ATP 1 FADH 2 ¡ 1.5 ATP 1 GTP ¡ 1 ATP 10 ATP

23.10 THE IMPORTANCE OF ATP The cycling of ATP and ADP in metabolic processes is the principal medium for energy exchange in biochemical processes. The conversion ATP ¡ ADP  Pi powers life processes (the biosynthesis of essential compounds, muscle contraction, nutrient transport, and so on). The conversion Pi  ADP ¡ ATP

ATP molecules in cells have a high turnover rate. Normally, a given ATP molecule in a cell does not last more than a minute before it is converted to ADP. The concentration of ATP in a cell varies from 0.5 to 2.5 milligram per milliliter of cellular fluid.

which occurs in food catabolism cycles, regenerates the ATP expended in cell operation. Figure 23.16 summarizes the ATP–ADP cycling process. ATP is a high-energy phosphate compound (Section 23.4). Its hydrolysis to ADP produces an intermediate amount of free energy (7.5 kcal/mole; Table 23.1) compared with hydrolysis energies for other organophosphate compounds (Table 23.1). Of major importance, the energy derived from ATP hydrolysis is a biochemically useful amount of energy. It is larger than the amount of energy needed by compounds to which ATP donates energy, and yet it is smaller than that available in compounds used to form ATP. If the ATP hydrolysis energy were unusually high, the body would not be able to convert ADP back to ATP because ATP synthesis requires an energy input equal to or greater than the hydrolysis energy, and such an unusually high amount of energy would not be available.

23.11 NON-ETC OXYGEN-CONSUMING REACTIONS The electron transport chain/oxidative phosphorylation phase of metabolism consumes more than 90% of the oxygen taken into the human body via respiration. What happens to the remainder of the inspired O2?

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23.11 Non-ETC Oxygen-Consuming Reactions

805

As a normal part of metabolic chemistry, significant amounts of this remaining O2 are converted into several highly reactive oxygen species (ROS). Among these ROSs are hydrogen peroxide (H2O2), superoxide ion (O2), and hydroxyl radical (OH). The latter two of these substances are free radicals, substances that contain an unpaired electron (Section 11.7). Reactive oxygen species have beneficial functions within the body, but they can also cause problems if they are not eliminated when they are no longer needed. White blood cells have a significant concentration of superoxide free radicals. Here, these free radicals aid in the destruction of invading bacteria and viruses. Their formation reaction is 2O2 1 NADPH ¡ 2O22 1 NADP 1 1 H 1 (NADP is a phosphorylated version of the coenzyme NADH; see Section 24.8.)

c

HEMICAL

onnections

Flavonoids: An Important Class of Dietary Antioxidants

Numerous studies indicate that diets high in fruits and vegetables are associated with a “healthy lifestyle.” One reason for this is that fruits and vegetables contain compounds called phytochemicals. Phytochemicals are compounds found in plants that have biochemical activity in the human body even though they have no nutritional value. The functions that phytochemicals perform in the human body include antioxidant activity, cancer inhibition, cholesterol regulation, and anti-inflammatory activity. Each fruit and vegetable is a unique package of phytochemicals, so consuming a wide variety of fruits and vegetables provides the body with the broadest spectrum of benefits. In such a situation, many phytochemicals are consumed in small amounts. This approach is much safer than taking supplemental doses of particular phytochemicals; in larger doses, some phytochemicals are toxic. A major group of phytochemicals are the flavonoids, of which over 4000 individual compounds are known. All flavonoids are antioxidants (Section 14.14), but some are stronger antioxidants than others, depending on their molecular structure. About 50 flavonoids are present in foods and in beverages derived from plants (tea leaves, grapes, oranges, and so on). The core flavonoid structure is

O

Both aromatic and cyclic ether ring systems are present. Of particular importance as antioxidants in foods are flavonoids known as flavones and flavonols, flavonoids whose core structures are enhanced by the presence of ketone and/or hydroxyl groups and a double bond in the oxygen-containing ring system.

O

O

O

O

OH Flavones

Flavonols

The formation of flavone and flavonol compounds depends normally on the action of light, so in general the highest concentration of these compounds occurs in leaves or in the skins of fruits, whereas only traces are found in parts of plants that grow below the ground. The common onion is, however, a wellknown exception to this generalization. The most widespread flavonoid in food is the flavonol quercetin. OH O

HO

OH OH

OH

O

It is predominant in fruits, vegetables, and the leaves of various vegetables. In fruits, apples contain the highest amounts of quercetin, the majority of it being found in the outer tissues (skin, peel). A small peeled apple contains about 5.7 mg of the antioxidant vitamin C. But the same amount of apple with the skin contains flavonoids and other phytochemicals that have the effect of 1500 mg of vitamin C. Onions are also major dietary sources of quercetin. In addition to their antioxidant benefits, flavonoids may also help fight bacterial infections. Recent studies indicate that flavonoids can stop the growth of some strains of drug-resistant bacteria.

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Chapter 23 Biochemical Energy Production

Superoxide ion that is not needed is eliminated from cells in a two-step process governed by the enzymes superoxide dismutase and catalase, two of the most rapidly working enzymes known (see Table 21.2). In the first step, superoxide ion is converted to hydrogen peroxide, which is then, in the second step, converted to H2O. superoxide dismutase

2O2  2H 888888n H2O2  O2 catalase 2H2O2 88888n 2H2O  O2 Immediate destruction of the hydrogen peroxide produced in the first of these two steps is critical, because if it persisted, then unwanted production of hydroxyl radical would occur via hydrogen peroxide’s reaction with superoxide ion. H2O2 1 O22 1 H 1 ¡ H2O 1 O2 1 OH

Antioxidant molecules provide electrons to convert free radicals and other ROSs into less-reactive substances.

c

Hydroxyl radicals quickly react with other substances by taking an electron from them. Such action usually causes bond breaking. Lipids in cell membranes are particularly vulnerable to such attack by hydroxyl radicals. It is estimated that 5% of the ROSs escape destruction through normal channels (superoxide dimutase and catalase). Operating within a cell is a backup system—a network of antioxidants—to deal with this problem. Participating in this antioxidant network are glutathione (Section 20.7), vitamin C (Section 21.12), and beta-carotene and vitamin E (Section 21.13), as well as other compounds obtained from plants through dietary intake. Particularly important in this latter category are compounds called flavonoids (see the Chemical Connections feature on page 805). The vitamin antioxidants as well as the other antioxidants present prevent oxidative damage by reacting with the harmful ROS oxidizing agents before they can react with other biologically important substances. Reactive oxygen species can also be formed in the body as the result of external influences such as polluted air, cigarette smoke, and radiation exposure (including solar radiation). Vitamin C is particularly active against such free-radical damage.

O N C E P TS TO R E M E M B E R

Metabolism. Metabolism is the sum total of all the biochemical reactions that take place in a living organism. Metabolism consists of catabolism and anabolism. Catabolic biochemical reactions involve the breakdown of large molecules into smaller fragments. Anabolic biochemical reactions synthesize large molecules from smaller ones (Section 23.1). Mitochondria. Mitochondria are membrane-enclosed subcellular structures that are the site of energy production in the form of ATP molecules. Enzymes for both the citric acid cycle and the electron transport chain are housed in the mitochondria (Section 23.2). Important coenzymes. Three very important coenzymes involved in catabolism are NAD, FAD, and CoA. NAD and FAD are oxidizing agents that participate in the oxidation reactions of the citric acid cycle. They transport hydrogen atoms and electrons from the citric acid cycle to the electron transport chain. CoA interacts with acetyl groups produced from food degradation to form acetyl CoA. Acetyl CoA is the “fuel” for the citric acid cycle (Section 23.3). High-energy compounds. A high-energy compound liberates a larger-than-normal amount of free energy upon hydrolysis because structural features in the molecule contribute to repulsive strain in one

or more bonds. Most high-energy biochemical molecules contain phosphate groups (Section 23.4). Common metabolic pathway. The common metabolic pathway includes the reactions of the citric acid cycle and those of the electron transport chain and oxidative phosphorylation. The degradation products from all types of foods (carbohydrates, fats, and proteins) participate in the reactions of the common metabolic pathway (Section 23.5). Citric acid cycle. The citric acid cycle is a cyclic series of eight reactions that oxidize the acetyl portion of acetyl CoA, resulting in the production of two molecules of CO2. The complete oxidation of one acetyl group produces three molecules of NADH, one of FADH2, and one of GTP besides the CO2 (Section 23.6). Electron transport chain. The electron transport chain is a series of reactions that passes electrons from NADH and FADH2 to molecular oxygen. Each electron carrier that participates in the chain has an increasing affinity for electrons. Upon accepting the electrons and hydrogen ions, the O2 is reduced to H2O (Section 23.7). Oxidative phosphorylation. Oxidative phosphorylation is the biochemical process by which ATP is synthesized from ADP as the result of a proton gradient across the inner mitochondrial membrane.

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Exercises and Problems

Oxidative phosphorylation is coupled to the reactions of the electron transport chain (Section 23.8). Chemiosmotic coupling. Chemiosmotic coupling explains how the energy needed for ATP synthesis is obtained. Synthesis takes place because of a flow of protons across the inner mitochondrial membrane (Section 23.8).

k

807

Importance of ATP. ATP is the link between energy production and energy use in cells. The conversion of ATP to ADP powers life processes, and the conversion of ADP back to ATP regenerates the energy expended in cell operation (Section 23.10).

EY R E A C T I O N S A N D E Q U AT I O N S

1. Oxidation by FAD (Section 23.3) ⫹

4. The electron transport chain (Section 23.7) ⫺

FAD ⫹ 2H ⫹ 2e

¡ FADH 2

NADH ⫹ H⫹ ¡ NAD ⫹ ⫹ 2H⫹ ⫹ 2e⫺ FADH 2 ¡ FAD ⫹ 2H⫹ ⫹ 2e⫺

⫹

2. Oxidation by NAD (Section 23.3) NAD ⫹ ⫹ 2H⫹ ⫹ 2e⫺ ¡ NADH ⫹ H⫹ 3. The citric acid cycle (Section 23.6)

O2 1 4H 1 1 4e 2 ¡ 2H2O 5. Oxidative phosphorylation (Section 23.8)

Acetyl CoA ⫹ 3NAD ⫹ ⫹ FAD ⫹ GDP ⫹ Pi ⫹ 2H2O ¡ 2CO2 ⫹ CoAOSH ⫹ 3NADH ⫹ 2H⫹ ⫹ FADH 2 ⫹ GTP

Energy

ADP ⫹ Pi 888888n ATP ⫹ H2O from ETC

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Metabolism (Section 23.1) 23.1 Classify anabolism and catabolism as synthetic or degradative

processes.

23.2 Classify anabolism and catabolism as energy-producing or

energy-consuming processes.

23.3 What is a metabolic pathway? 23.4 What is the difference between a linear and a cyclic metabolic

pathway?

23.5 What general characteristics are associated with a catabolic

pathway? 23.6 What general characteristics are associated with an anabolic pathway?

Intermediate Compounds in Metabolic Pathways (Section 23.3) 23.15 What does each letter in ATP stand for? 23.16 What does each letter in ADP stand for? 23.17 Draw a block diagram structure for ATP. 23.18 Draw a block diagram structure for ADP. 23.19 What is the structural difference between ATP and AMP? 23.20 What is the structural difference between ADP and AMP? 23.21 What is the structural difference between ATP and GTP? 23.22 What is the structural difference between ATP and CTP? 23.23 In terms of hydrolysis, what is the relationship between ATP

and ADP?

Cell Structure (Section 23.2) 23.7 List several differences between prokaryotic cells and eukaryotic

cells.

23.8 What kinds of organisms have prokaryotic cells and what kinds

have eukaryotic cells?

23.9 What is an organelle? 23.10 What is the general function of each of the following types of

organelles? a. Ribosome b. Lysosome c. Mitochondrion 23.11 In a mitochondrion, what separates the matrix from the intermembrane space? 23.12 In what major way do the inner and outer mitochondrial membranes differ? 23.13 What is the intermembrane space of a mitochondrion? 23.14 Where are ATP synthase complexes located in a

mitochondrion?

23.24 In terms of hydrolysis, what is the relationship between ADP

and AMP?

23.25 What does each letter in FAD stand for? 23.26 What does each letter in NAD⫹ stand for? 23.27 Draw a block diagram structure for FAD based on the presence

of an ADP core (three-block diagram). 23.28 Draw a block diagram structure for FAD based on the presence of two nucleotides (six-block diagram).

23.29 Draw a block diagram structure for NAD⫹ based on the presence

of two nucleotides (six-block diagram).

23.30 Draw a block diagram structure for NAD⫹ based on the presence

of an ADP core (three-block diagram).

23.31 Which part of an NAD⫹ molecule is the active participant in

redox reactions?

23.32 Which part of an FAD molecule is the active participant in

redox reactions?

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Chapter 23 Biochemical Energy Production

23.33 Give the letter designation for

a. the reduced form of FAD. b. the oxidized form of NADH. 23.34 Give the letter designation for a. the oxidized form of FADH2. b. the reduced form of NAD.

c. How many decarboxylation reactions occur? d. How many oxidation–reduction reactions occur? 23.53 There are eight steps in the citric acid cycle. List those steps

b. FAD. a. NAD. 23.36 Indicate whether or not the vitamin B portion of the following molecules is the “active” portion of the molecule in redox processes. b. FAD. a. NAD.

that involve a. oxidation. b. isomerization. c. hydration. 23.54 There are eight steps in the citric acid cycle. List those steps that involve a. oxidation and decarboxylation. b. phosphorylation. c. condensation.

23.37 Draw the three-block diagram structure for coenzyme A.

23.55 There are four C4 dicarboxylic acid species in the citric acid

23.35 Name the vitamin B molecule that is part of the structure of

23.38 Which part of a coenzyme A molecule is the active participant

in an acetyl transfer reaction?

High-Energy Phosphate Compounds (Section 23.4) 23.39 What is a high-energy compound?

cycle. What are their names and structures? 23.56 There are two keto carboxylic acid species in the citric acid cycle. What are their names and structures?

23.57 What type of reaction occurs in the citric acid cycle whereby

a C6 compound is converted to a C5 compound?

23.40 What factors contribute to a strained bond in high-energy

23.58 What type of reaction occurs in the citric acid cycle whereby

23.41 What does the designation Pi denote?

23.59 Identify the oxidized coenzyme (NAD or FAD) that partici-

phosphate compounds?

23.42 What does the designation PPi denote? 23.43 With the help of Table 23.1, determine which compound in

each of the following pairs of phosphate-containing compounds releases more free energy upon hydrolysis. a. ATP and phosphoenolpyruvate b. Creatine phosphate and ADP c. Glucose 1-phosphate and 1,3-bisphosphoglycerate d. AMP and glycerol 3-phosphate 23.44 With the help of Table 23.1, determine which compound in each of the following pairs of phosphate-containing compounds releases more free energy upon hydrolysis. a. ATP and creatine phosphate b. Glucose 1-phosphate and glucose 6-phosphate c. ADP and AMP d. Phosphoenolpyruvate and PPi Biochemical Energy Production (Section 23.5) 23.45 Describe the four general stages of the process by which

biochemical energy is obtained from food.

23.46 Of the four general stages of biochemical energy production

from food, which are part of the common metabolic pathway?

The Citric Acid Cycle (Section 23.6) 23.47 What are two other names for the citric acid cycle? 23.48 What is the basis for the name citric acid cycle? 23.49 What is the “fuel” for the citric acid cycle? 23.50 What are the products of the citric acid cycle? 23.51 Consider the reactions that occur during one turn of the citric

acid cycle in answering each of the following questions. a. How many CO2 molecules are formed? b. How many molecules of FADH2 are formed? c. How many times is a secondary alcohol oxidized? d. How many times does water add to a carbon–carbon double bond? 23.52 Consider the reactions that occur during one turn of the citric acid cycle in answering each of the following questions. a. How many molecules of NADH are formed? b. How many GTP molecules are formed?

a C5 compound is converted to a C4 compound?

pates in each of the following citric acid cycle reactions. a. Isocitrate ¡ a-ketoglutarate b. Succinate ¡ fumarate 23.60 Identify the oxidized coenzyme (NAD or FAD) that participates in each of the following citric acid cycle reactions. a. Malate ¡ oxaloacetate b. a-Ketoglutarate ¡ succinyl CoA 23.61 List the two citric acid cycle intermediates involved in the

reaction governed by each of the following enzymes. List the reactant first. a. Isocitrate dehydrogenase b. Fumarase c. Malate dehydrogenase d. Aconitase 23.62 List the two citric acid cycle intermediates involved in the reaction governed by each of the following enzymes. List the reactant first. a. a-Ketoglutarate dehydrogenase b. Succinate dehydrogenase c. Citrate synthase d. Succinyl CoA synthetase

The Electron Transport Chain (Section 23.7) 23.63 By what other name is the electron transport chain known? 23.64 Give a one-sentence summary of what occurs during the

reactions known as the electron transport chain.

23.65 What is the final electron acceptor of the electron transport

chain? 23.66 Which substances generated in the citric acid cycle participate in the electron transport chain? 23.67 Give the abbreviation for each of the following electron carriers.

a. The oxidized form of flavin mononucleotide b. The reduced form of coenzyme Q 23.68 Give the abbreviation for each of the following electron carriers. a. The reduced form of flavin mononucleotide b. The oxidized form of coenzyme Q

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Exercises and Problems

23.69 Indicate whether each of the following electron carriers is in

its oxidized form or its reduced form. a. Fe(III)SP b. Cyt b (Fe3) c. NADH d. FAD 23.70 Indicate whether each of the following electron carriers is in its oxidized form or its reduced form. b. Fe(II)SP a. FMNH2 d. NAD c. Cyt c1 (Fe2) 23.71 Indicate whether each of the following changes represents

oxidation or reduction. a. CoQH2 ¡ CoQ b. NAD 1 ¡ NADH c. Cyt c 1Fe21 2 ¡ cyt c 1Fe31 2 d. Cyt b 1Fe31 2 ¡ cyt b 1Fe21 2 23.72 Indicate whether each of the following changes represents oxidation or reduction. a. FADH2 ¡ FAD b. FMN ¡ FMNH2 c. Fe1III2SP ¡ Fe1II2SP d. Cyt c1 1Fe31 2 ¡ cyt c1 1Fe21 2

23.73 With which of the protein complexes (I, II, III, and IV) of the

ETC is each of the following electron carriers associated? More than one answer may apply in a given situation. a. NADH b. CoQ c. Cyt b d. Cyt a 23.74 With which of the protein complexes (I, II, III, and IV) of the ETC is each of the following electron carriers associated? More than one answer may apply in a given situation. b. FeSP c. Cyt c d. Cyt c1 a. FADH2 23.75 Which electron carrier shuttles electrons between protein 23.76

complexes I and III? Which electron carrier shuttles electrons between protein complexes II and III?

23.77 How many electrons does the electron carrier between complexes 23.78

II and III carry per “trip”? How many electrons does the electron carrier between complexes III and IV carry per “trip”?

23.79 Fill in the missing substances in the following electron trans-

port chain reaction sequences. 2Fe(III)SP a. FAD

b.

? ?

? 2Fe3

? CoQ

?

FeSP FMN 23.80

?

CoQ

Fill in the missing substances in the following electron transport chain reaction sequences. ? ? ? a.

NADH

FMN

2Fe(II)SP

b. CoQH2

? FeSP

? Cyt b

2Fe2

2Fe3

?

Oxidative Phosphorylation (Section 23.8) 23.81 What is oxidative phosphorylation? 23.82

What are coupled reactions?

809

23.83 The coupling of ATP synthesis with the reactions of the ETC

23.84 23.85 23.86

23.87 23.88

is related to the movement of what chemical species across the inner mitochrondial membrane? At what protein complex location(s) in the electron transport chain does proton pumping occur? At what mitochondrial location does H ion buildup occur as the result of proton pumping? How many protons cross the inner mitochondrial membrane for every two electrons that are passed through the electron transport chain? What is the name of the enzyme that catalyzes ATP production during oxidative phosphorylation? What is the location of the enzyme that uses stored energy in a proton gradient to drive the reaction that produces ATP?

23.89 How is the proton gradient associated with chemiosmotic 23.90

coupling dissipated during ATP synthesis? What are the “starting materials” from which ATP is synthesized as the proton gradient associated with chemiosmotic coupling is dissipated?

ATP Production (Section 23.9) 23.91 How many ATP molecules are formed for each NADH molecule

that enters the electron transport chain? How many ATP molecules are formed for each FADH2 molecule that enters the electron transport chain? 23.93 NADH and FADH2 molecules do not yield the same number of ATP molecules. Explain why. 23.94 What is the energy yield, in terms of ATP molecules, from one turn of the citric acid cycle, assuming that the products of the cycle enter the electron transport chain? 23.92

The Importance of ATP (Section 23.10) 23.95 How does the free-energy release associated with the hydrolysis of ATP to ADP compare with the hydrolysis energies of other high-energy phosphate compounds? 23.96 What would the biochemical consequences be if the freeenergy release associated with the hydrolysis of ATP to ADP had an unusually high value? 23.97 Indicate whether each of the following processes would be expected to involve the conversion of ATP to ADP or the conversion of ADP to ATP. a. Heart muscle contraction b. Transport of nutrients to various locations in the body 23.98 Indicate whether each of the following processes would be expected to involve the conversion of ATP to ADP or the conversion of ADP to ATP. a. Degradation of dietary carbohydrates b. Synthesis of protein from amino acids Non-ETC Oxygen-Consuming Reactions (Section 23.11) 23.99 What does the designation ROS stand for? 23.100 Give the chemical formula for each of the following. a. Superoxide ion b. Hydroxyl radical 23.101 Give the chemical equation for the reaction by which a. superoxide ion is generated within cells. b. superoxide ion is converted to hydrogen peroxide within cells. 23.102 Give the chemical equation for the reaction by which a. hydrogen peroxide is converted to desirable products within cells. b. hydrogen peroxide is converted to an undesirable product within cells.

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Chapter 23 Biochemical Energy Production

A DD D IT IO NAL P R O BL L EM S 23.103 Classify each of the following substances as (1) a reactant in

the citric acid cycle, (2) a reactant in the electron transport chain, or (3) a reactant in both the CAC and the ETC. a. NADH b. O2 c. Fumarate d. Cytochrome a 23.104 Classify each of the following substances as (1) a product in the citric acid cycle, (2) a product in the electron transport chain, or (3) a product in both the CAC and the ETC. a. FAD b. CO2 c. Malate d. Flavin mononucleotide 23.105 Which of these substances, (1) ATP, (2) CoA, (3) FAD, and (4) NAD, contain the following subunits of structure? More than one choice may apply in a given situation. a. Contains two ribose subunits b. Contains two phosphate subunits c. Contains one adenine subunit d. Contains one ribitol subunit 23.106 Characterize, in terms of number of carbon atoms present, each of the following citric acid cycle changes as (1) a C6 to

C6 change, (2) a C6 to C5 change, (3) a C5 to C4 change, or (4) a C4 to C4 change. a. Citrate to isocitrate b. Succinate to fumarate c. Malate to oxaloacetate d. Isocitrate to a-ketoglutarate 23.107 In what way are the processes of the citric acid cycle and the electron transport chain interrelated? 23.108 Where within a cell does each of the following take place? a. Citric acid cycle b. Electron transport chain and oxidative phosphorylation 23.109 One of the oxidation steps that occurs when lipids are metabolized is

O O B B ROCH2OCH2OCOSOCoA8n ROCHPCHOCOSOCoA Would you expect this reaction to require FAD or NAD as the oxidizing agent? 23.110 In oxidative phosphorylation, what is oxidized and what is phosphorylated?

multiple-Choice Practice Test 23.111 Which of the following is true for a mitochondrion?

23.112

23.113

23.114

23.115

a. The inner membrane separates the matrix from the intermembrane space. b. The inner membrane is more permeable than the outer membrane. c. The outer membrane has ATP-synthase complexes attached to it. d. The outer membrane has a highly folded structure. Which of the following molecules has two unsubstituted ribose molecules as structural subunits? c. CoA d. ATP a. FAD b. NAD Which of the following are products of the citric acid cycle? a. Acetyl CoA and NADH b. Acetyl CoA and CO2 c. CO2 and H2O d. CO2 and FADH2 Which of the following citric acid cycle intermediates is not a C4 species? a. Fumarate b. Citrate c. Malate d. Oxaloacetate Which are the first two intermediates, respectively, in the citric acid cycle? a. Isocitrate and a-ketoglutarate b. Citrate and a-ketoglutarate c. Citrate and isocitrate d. Isocitrate and succinate

23.116 Which of the following is an electron carrier that shuttles

23.117

23.118

23.119

23.120

electrons between various protein complexes in the electron transport chain? a. FMN b. NADH c. Cyt c d. Cyt a3 What is the substrate that interacts with protein complex III in the electron transport chain? b. Cyt c1 a. CoQH2 c. FMN d. FeSP Which of the following is both a reactant and a product in the operation of the electron transport chain? b. H2O a. O2 d. Cyt b c. FADH2 At how many protein complex sites in the electron transport chain does proton pumping occur? a. One b. Two c. Three d. Four How many moles of ATP result from the entry of one mole of NADH into the electron transport chain? a. 1 mole ATP b. 1.5 moles ATP c. 2 moles ATP d. 2.5 moles ATP

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Carbohydrate Metabolism Chapter Outline 24.1 Digestion and Absorption of Carbohydrates 811 24.2 Glycolysis 813

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24.3 Fates of Pyruvate 822 24.4 ATP Production for the Complete Oxidation of Glucose 826 24.5 Glycogen Synthesis and Degradation 828 24.6 Gluconeogenesis 830 24.7 Terminology for Glucose Metabolic Pathways 832 24.8 The Pentose Phosphate Pathway 833

CHEMISTRY AT A GLANCE: Glucose Metabolism 835 24.9 Hormonal Control of Carbohydrate Metabolism 835

CHEMICAL CONNECTIONS

Carbohydrates are the major energy source for human beings.

Lactate Accumulation 825 Diabetes Mellitus 836

I

n this chapter we explore the relationship between carbohydrate metabolism and energy production in cells. The molecule glucose is the focal point of carbohydrate metabolism. Commonly called blood sugar, glucose is supplied to the body via the circulatory system and, after being absorbed by a cell, can be either oxidized to yield energy or stored as glycogen for future use. When sufficient oxygen is present, glucose is totally oxidized to CO2 and H2O. However, in the absence of oxygen, glucose is only partially oxidized to lactic acid. Besides supplying energy needs, glucose and other sixcarbon sugars can be converted into a variety of different sugars (C3, C4, C5, and C7) needed for biosynthesis. Some of the oxidative steps in carbohydrate metabolism also produce NADH and NADPH, sources of reductive power in cells.

24.1 DIGESTION AND ABSORPTION OF CARBOHYDRATES

Salivary a-amylase is a constituent of saliva, the fluid secreted by the salivary glands. Saliva is 99% water plus small amounts of several inorganic ions and organic molecules. Saliva secretion can be triggered by the taste, smell, sight, and even thought of food. Average saliva output is about 1.5 L per day.

Digestion is the biochemical process by which food molecules, through hydrolysis, are broken down into simpler chemical units that can be used by cells for their metabolic needs. Digestion is the first stage in the processing of food products. The digestion of carbohydrates begins in the mouth, where the enzyme salivary a-amylase catalyzes the hydrolysis of a-glycosidic linkages (Section 18.13) in starch from plants and glycogen from meats to produce smaller polysaccharides and the disaccharide maltose. Only a small amount of carbohydrate digestion occurs in the mouth because food is swallowed so quickly. Although the food mass remains longer in the stomach, very little further carbohydrate digestion occurs there either, because salivary a-amylase is

811

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Chapter 24 Carbohydrate Metabolism

Figure 24.1 A section of the small intestine, showing its folds and the villi that cover the inner surface of the folds. Villi greatly increase the inner intestinal surface area.

Villi

Folds of inner intestinal wall

inactivated by the acidic environment of the stomach, and the stomach’s own secretions do not contain any carbohydrate-digesting enzymes. The primary site for carbohydrate digestion is within the small intestine, where a-amylase, this time secreted by the pancreas, again begins to function. The pancreatic a-amylase breaks down polysaccharide chains into shorter and shorter segments until the disaccharide maltose (two glucose units; Section 18.13) and glucose itself are the dominant species. The final step in carbohydrate digestion occurs on the outer membranes of intestinal mucosal cells, where the enzymes that convert disaccharides to monosaccharides are located. The important disaccharidase enzymes are maltase, sucrase, and lactase. These enzymes convert, respectively, maltose to two glucose units, sucrose to one glucose and one fructose unit, and lactose to one glucose and one galactose unit (Section 18.13). (The disaccharides sucrose and lactose present in food are not digested until they reach this point.) The three major breakdown products from carbohydrate digestion are thus glucose, galactose, and fructose. These monosaccharides are absorbed into the bloodstream through the intestinal wall. The folds of the intestinal wall are lined with fingerlike projections called villi, which are rich in blood capillaries (Figure 24.1). Absorption is by active transport (Section 19.10), which, unlike passive transport, is an energy-requiring process. In this case, ATP is needed. Protein carriers mediate the passage of the monosaccharides through cell membranes. Figure 24.2 summarizes the different phases in the digestive process for carbohydrates. After their absorption into the bloodstream, monosaccharides are transported to the liver, where fructose and galactose are rapidly converted into compounds that are metabolized by the same pathway as glucose. Thus the central focus of carbohydrate metabolism is the pathway by which glucose is further processed, a pathway called glycolysis (Section 24.2)—a series of ten reactions, each of which involves a different enzyme.

EXAMPLE 24.1 Determining the Sites Where Various Aspects of Carbohydrate Digestion Occur

Based on the information in Figure 24.2, determine the location within the human body where each of the following aspects of carbohydrate digestion occurs. a. b. c. d.

The enzyme sucrase is active. Hydrolysis reactions converting polysaccharides to disaccharides occur. First site where breaking of glycosidic linkages occurs. The monosaccharides glucose, fructose, and galactose are produced. (continued)

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24.2 Glycolysis

Polysaccharides, maltose, sucrose, lactose

Dietary carbohydrates

1. Mouth

813

Salivary α-amylase—hydrolysis of some α-glycosidic linkages

2. Stomach

Gastric juice—no effect on digestion

Monosaccharides in bloodstream

5. Intestinal Lining (Villi)

Figure 24.2 Summary of carbohydrate digestion in the human body.

Active transport

3. Small Intestine

Pancreatic digestive enzymes—hydrolysis of polysaccharides to disaccharides

Maltose, sucrose, lactose

Glucose, fructose, galactose

4. Intestinal Mucosal Cells

Maltase Sucrase Lactase

Hydrolysis of disaccharides

Solution

a. Intestinal mucosal cells are the sites where hydrolysis of disaccharides, effected by the enzymes maltase, sucrase, and lactase, occurs. b. The small intestine is the location where pancreatic digestive enzymes convert polysaccharides to disaccharides. c. Digestion of carbohydrates begins in the mouth, where salivary enzymes convert some polysaccharides to smaller polysaccharides through breakage of glycosidic linkages. d. Intestinal mucosal cells are the sites where disaccharides, through hydrolysis, are converted to the monosaccharides glucose, fructose, and galactose.

Practice Exercise 24.1 Based on the information in Figure 24.2, determine the location within the human body where each of the following aspects of carbohydrate digestion occurs.

The term glycolysis, pronounced “gligh-KOLL-ih-sis,” comes from the Greek glyco, meaning “sweet,” and lysis, meaning “breakdown.” B

F

Pyruvate, pronounced “PIE-roovate,” is the carboxylate ion (Section 16.8) produced when pyruvic acid (a three-carbon keto acid) loses its acidic hydrogen atom. CH3 A C PO A COOH Pyruvic acid

CH3 A C PO  H A COO Pyruvate ion

a. b. c. d.

Pancreatic enzymes are active. Hydrolysis reactions converting disaccharides to monosaccharides occur. Monosaccharides enter the bloodstream. The primary site for carbohydrate digestion is located.

Answers: a. Small intestine; b. Intestinal mucosal cells; c. Intestinal lining villi; d. Small intestine

24.2 GLYCOLYSIS Glycolysis is the metabolic pathway by which glucose (a C6 molecule) is converted into two molecules of pyruvate (a C3 molecule), chemical energy in the form of ATP is produced, and NADH-reduced coenzymes are produced. This metabolic pathway functions in almost all cells. The conversion of glucose to pyruvate is an oxidation process in which no molecular oxygen is utilized. The oxidizing agent is the coenzyme NAD. Metabolic pathways in which molecular oxygen is not a participant are called anaerobic pathways. Pathways that require molecular oxygen are called aerobic pathways. Glycolysis is an anaerobic pathway.

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Chapter 24 Carbohydrate Metabolism

Anaerobic is pronounced “AN-airROE-bic.” Aerobic is pronounced “air-ROE-bic.” Glycolysis is also called the Embden–Meyerhof pathway after the German chemists Gustav Embden (1874–1933) and Otto Meyerhof (1884–1951), who discovered many of the details of the pathway in the early 1930s.

Glycolysis is a ten-step process (compared to the eight steps of the citric acid cycle; Section 23.6) in which every step is enzyme-catalyzed. Figure 24.3 gives an overview of glycolysis. There are two stages in the overall process, a six-carbon stage (Steps 1–3) and a three-carbon stage (Steps 4–10). All of the enzymes needed for glycolysis are present in the cell cytosol (Section 23.2), which is where glycolysis takes place. Details of the individual steps within the glycolysis pathway are now considered.

Six-Carbon Stage of Glycolysis (Steps 1–3) The six-carbon stage of glycolysis is an energy-consuming stage. The energy release associated with the conversion of two ATP molecules to two ADP molecules is used to transform monosaccharides into monosaccharide phosphates. The intermediates of the six-carbon stage of glycolysis are all either glucose or fructose derivatives in which phosphate groups are present. Step 1:

B

F

A kinase is an enzyme that catalyzes the transfer of a phosphoryl group (PO32) from ATP (or some other high-energy phosphate compound) to a substrate (Section 21.3).

Phosphorylation: Formation of Glucose 6-Phosphate. Glycolysis begins with the phosphorylation of glucose to yield glucose 6-phosphate, a glucose molecule with a phosphate group attached to the hydroxyl oxygen on carbon 6 (the carbon atom outside the ring). The phosphate group is from an ATP molecule. Hexokinase, an enzyme that requires Mg2 ion for its activity, catalyzes the reaction.

H A H OO O C O H

H A P OO O C O H O

O ADP

ATP

HO

Step 1 of glycolysis is the first of two steps in which an ATP molecule is converted to an ADP with the energy released used to effect a phosphorylation. The other ATPphosphorylation reaction occurs in Step 3.

OH

Hexokinase

HO

OH OH

The symbol P is a shorthand notation for a PO32 unit.

OH

OH OH

Glucose

Glucose 6-phosphate

This reaction requires energy, which is provided by the breakdown of an ATP molecule. This energy expenditure will be recouped later in the cycle. Phosphorylation of glucose provides a way of “trapping” glucose within a cell. Glucose can cross cell membranes, but glucose 6-phosphate cannot. Step 2: Isomerization: Formation of Fructose 6-Phosphate. Glucose 6-phosphate is isomerized to fructose 6-phosphate by phosphoglucoisomerase. P O O O CH2 O

HO

1

OH 3

2

OH Glucose 6-phosphate

Step 3 of glycolysis commits the original glucose molecule to the glycolysis pathway. Glucose 6-phosphate (Step 1) and fructose 6-phosphate (Step 2) can enter other metabolic pathways, but fructose 1,6-bisphosphate can enter only glycolysis.

Phosphoglucoisomerase

P O O O CH2

1

O

CH2OH

HO

OH

3

2

OH

HO Fructose 6-phosphate

The net result of this change is that carbon 1 of glucose is no longer part of the ring structure. [Glucose, an aldose, forms a six-membered ring, and fructose, a ketose, forms a five-membered ring (Section 18.10); both sugars, however, contain six carbon atoms.] Step 3:

Phosphorylation: Formation of Fructose 1,6-Bisphosphate. This step, like Step 1, is a phosphorylation reaction and therefore requires the expenditure of energy. ATP is the source of the phosphate and the energy. The enzyme involved, phosphofructokinase, is another enzyme that requires Mg2 ion for its activity. The fructose molecule now contains two phosphate groups.

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24.2 Glycolysis

815

Figure 24.3 An overview of Glucose

glycolysis.

ATP Step 1

Hexokinase

ADP Glucose 6-phosphate

Step 2

C6 stage

Phosphoglucoisomerase

Fructose 6-phosphate

Step 3

ATP

Phosphofructokinase

ADP Fructose 1,6-bisphosphate

Step 4

Aldolase

Step 5 Dihydroxyacetone phosphate

Two glyceraldehyde 3-phosphates

Triosephosphate isomerase

Step 6

Glyceraldehyde 3-phosphate dehydrogenase

2 NAD+ + 2 Pi 2 NADH + 2 H+

Two 1,3-bisphosphoglycerates

Step 7

Phosphoglycerokinase

2 ADP 2 ATP

Two 3-phosphoglycerates

Step 8

Phosphoglyceromutase

Two 2-phosphoglycerates

Step 9

Enolase

2 H2O

Two phosphoenolpyruvates

Step 10

2 ADP

Pyruvate kinase

2 ATP Two pyruvates

C3 stage

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Chapter 24 Carbohydrate Metabolism

O

P O OH2C

Step 3 of glycolysis, like Step 1, is a step in which phosphorylation is effected as an ATP molecule is converted to an ADP molecule.

CH2OH

ATP

HO

ADP

CH2O O P

HO

Phosphofructokinase

OH

OH

HO

HO

Fructose 6-phosphate

The term bisphosphate is used instead of diphosphate to indicate the two phosphates are on different carbon atoms in fructose and not connected to each other.

O

P O OH2C

Fructose 1,6-bisphosphate

Three-Carbon Stage of Glycolysis (Steps 4–10) The three-carbon stage of glycolysis is an energy-generating stage rather than an energyconsuming stage. All of the intermediates in this stage are C3-phosphates, two of which are high-energy phosphate species (Section 23.4). Loss of a phosphate from these high-energy species effects the conversion of ADP molecules to ATP molecules. The C3 intermediates in this stage of glycolysis are all phosphorylated derivatives of dihydroxyacetone, glyceraldehyde, glycerate, or pyruvate, which in turn are derivatives of either glycerol or acetone. Figure 24.4 shows the structural relationships among these molecules. Step 4: Cleavage: Formation of Two Triose Phosphates. In this step, the reacting C6 species is split into two C3 (triose) species. Because fructose 1,6-bisphosphate, the molecule being split, is unsymmetrical, the two trioses produced are not identical. One product is dihydroxyacetone phosphate, and the other is glyceraldehyde 3-phosphate. Aldolase is the enzyme that catalyzes this reaction. A better understanding of the structural relationships between reactant and products is obtained if the fructose 1,6-bisphosphate is written in its open-chain form (Section 18.10) rather than in its cyclic form.

Figure 24.4 Structural

Glyceraldehyde

relationships among glycerol and acetone and the C3 intermediates in the process of glycolysis.

CHO H GLYCEROL

C

Glyceraldehyde 3-phosphate

OH

CH2OH

CH2OH H

C

OH

CH2OH

Glycerate COO– H

C

OH

1,3-Bisphosphoglycerate 3-Phosphoglycerate 2-Phosphoglycerate

CH2OH

Dihydroxyacetone CH2OH C ACETONE

O

Dihydroxyacetone phosphate

CH2OH

CH3 C O CH3

Pyruvate COO– C CH3

O

Phosphoenolpyruvate

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24.2 Glycolysis

1

CH2O O P A 2 CPO A 3 HO OC O H A 4 HOC O OH A 5 HOC OOH A 6 CH2OO P

817

1

CH2OO P H O A G4J CPO C A A 5 3 HO C OOH HO OC O H A A  6 H CH2OO P 2

Aldolase

Fructose 1,6-bisphosphate (open-chain form)

Dihydroxyacetone phosphate

Glyceraldehyde 3-phosphate

Step 5: Isomerization: Formation of Glyceraldehyde 3-Phosphate. Only one of the two trioses produced in Step 4, glyceraldehyde 3-phosphate, is a glycolysis intermediate. Dihydroxyacetone phosphate, the other triose, can, however, be readily converted into glyceraldehyde 3-phosphate. Dihydroxyacetone phosphate (a ketose) and glyceraldehyde 3-phosphate (an aldose) are isomers, and the isomerization process from ketose to aldose is catalyzed by the enzyme triosephosphate isomerase. CH2O O P A OPC A HO O C O H A H

Triosephosphate isomerase

CH2O O P A HO OC O H A C J G O H

Dihydroxyacetone phosphate

Step 6:

Step 6 is the first of two glycolysis steps in which a high-energy phosphate compound, that is an “energyrich” compound, is formed. The other high-energy phosphate compound is formed in Step 9. In the step that follows each of these two situations, energy from the highenergy phosphate compound is used to convert ADP to ATP.

Oxidation and Phosphorylation: Formation of 1,3-Bisphosphoglycerate. In a reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase, a phosphate group is added to glyceraldehyde 3-phosphate to produce 1,3-bisphosphoglycerate. The hydrogen of the aldehyde group becomes part of NADH.

O H M D C A  NAD  Pi HO C O OH A CH2OO P

O O⬃ P M D C A  NADH  H HO CO OH A CH2OO P

Glyceraldehyde 3-phosphate dehydrogenase

Glyceraldehyde 3-phosphate

1,3-Bisphosphoglycerate

The newly added phosphate group in 1,3-bisphosphoglycerate is a high-energy phosphate group (Section 23.4). A high-energy phosphate group is produced when a phosphate group is attached to a carbon atom that is also participating in a carbon–carbon or carbon–oxygen double bond. Note that a molecule of the reduced coenzyme NADH is a product of this reaction and also that the source of the added phosphate is inorganic phosphate (Pi).

Keep in mind that from Step 6 onward, two molecules of each of the C3 compounds take part in every reaction for each original C6 glucose molecule.

Step 7:

Step 7 is the first of two steps in which ATP is formed from ADP. This process, called substrate-level phosphorylation, always involves a high-energy phosphate compound. This same process also occurs in Step 10.

Glyceraldehyde 3-phosphate

Phosphorylation of ADP: Formation of 3-Phosphoglycerate. In this step, the diphosphate species just formed is converted back to a monophosphate species. This is an ATP-producing step in which the C-1 phosphate group of 1,3-bisphosphoglycerate (the high-energy phosphate) is transferred to an ADP molecule to form the ATP. The enzyme involved is phosphoglycerokinase. O O⬃ P M D C A HO CO OH A CH2OO P 1,3-Bisphosphoglycerate

ADP

ATP

Phosphoglycerokinase

O O M D C A HO CO OH A CH2OO P 3-Phosphoglycerate

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A mutase is an enzyme that effects the shift of a functional group from one position to another within a molecule (Section 21.2).

Remember that two ATP molecules are produced for each original glucose molecule because both C3 molecules produced from the glucose react. ATP production in this step involves substrate-level phosphorylation. Substrate-level phosphorylation is the biochemical process by which a highenergy phosphate group from an intermediate compound (substrate) is directly transferred to ADP to produce ATP. Substrate-level phosphorylation differs from oxidative phosphorylation (Section 23.8) in that the latter process involves the transfer of free phosphate ions in solution (Pi) to ADP molecules to form ATP. Step 8: Isomerization: Formation of 2-Phosphoglycerate. In this isomerization step, the phosphate group of 3-phosphoglycerate is moved from carbon 3 to carbon 2. The enzyme phosphoglyceromutase catalyzes the exchange of the phosphate group between the two carbons. O O M D C A HO CO OH A CH2OO P

Phosphoglyceromutase

2-Phosphoglycerate

3-Phosphoglycerate

An enol (from ene  ol), as in phosphoenolpyruvate, is a compound in which an —OH group is attached to a carbon atom involved in a carbon– carbon double bond. Note that in phosphoenolpyruvate, the —OH group has been phosphorylated.

Step 9 is the second of two glycolytic steps in which a high-energy phosphate compound, that is, “energy-rich” compound, is formed; the other step was Step 6. In the next step, energy from the high-energy phosphate compound will be used to convert ADP and ATP. Step 10 is the second of two steps in which ATP is formed from ADP. This same process also occurred in Step 7.

Step 9:

O O M D C A HO CO OO P A CH2OH

Dehydration: Formation of Phosphoenolpyruvate. This is an alcohol dehydration reaction that proceeds with the enzyme enolase, another Mg2-requiring enzyme. The result is another compound containing a high-energy phosphate group; the phosphate group is attached to a carbon atom that is involved in a carbon–carbon double bond. O O M D C A H O CO OO P A HO O CO H A H

O O M D C A C O O⬃ P  HOH B C D G H H

Enolase

Phosphoenolpyruvate

2-Phosphoglycerate

Step 10: Phosphorylation of ADP: Formation of Pyruvate. In this step, substrate-level phosphorylation again occurs. Phosphoenolpyruvate transfers its high-energy phosphate group to an ADP molecule to produce ATP and pyruvate. O O M D C A C O O⬃ P B C D G H H Phosphoenolpyruvate

ADP

ATP

Pyruvate kinase

O O M D C A CPO A CH3 Pyruvate

The enzyme involved, pyruvate kinase, requires both Mg2 and K ions for its activity. Again, because two C3 molecules are reacting, two ATP molecules are produced. ATP molecules are involved in Steps 1, 3, 7, and 10 of glycolysis. Considering these steps collectively shows that there is a net gain of two ATP molecules for every glucose molecule converted into two pyruvates (Table 24.1). Though useful, this is a small amount of ATP compared to that generated in oxidative phosphorylation (Section 23.8). The net overall equation for the process of glycolysis is Glucose  2NAD  2ADP  2Pi ¡

2 pyruvate  2NADH  2ATP  2H  2H2O

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TABLE 24.1 ATP Production and Consumption During Glycolysis

EXAMPLE 24.2 Recognizing Structural Characteristics of Glycolysis Intermediates

Step

Reaction

1 3 7 10

Glucose : glucose 6-phosphate Fructose 6-phosphate : fructose 1,6-bisphosphate 2(1,3-Bisphosphoglycerate : 3-phosphoglycerate) 2(Phosphoenolpyruvate : pyruvate)

ATP Change per Glucose

⫺1 ⫺1 ⫹2 ⫹2 Net ⫹2

Specify the number of carbon atoms present and the number of phosphate groups present in each of the following glycolysis intermediates. a. b. c. d.

Glucose 6-phosphate Fructose 1,6-bisphosphate Glyceraldehyde 3-phosphate 3-Phosphoglycerate

Solution

a. Glucose is a hexose. It is a C6 molecule that carries one phosphate group, attached to carbon 6. b. Fructose is also a hexose. It is a C6 molecule that carries two phosphate groups, one attached to carbon 1 and the other attached to carbon 6. c. Glyceraldehyde is a C3 molecule with one phosphate group, attached to carbon 3. d. Glycerate, like glyceraldehyde, is a C3 molecule with one phosphate group, attached to carbon 3.

Practice Exercise 24.2 Specify the number of carbon atoms present and the number of phosphate groups present in each of the following glycolysis intermediates. a. b. c. d.

Fructose 6-phosphate 1,3-Bisphosphoglycerate 2-Phosphoglycerate Phosphoenolpyruvate

Answers: a. C6 with one phosphate; b. C3 with two phosphates; c. C3 with one phosphate;

d. C3 with one phosphate

EXAMPLE 24.3 Recognizing Reaction Types and Events That Occur in the Various Steps of Glycolysis

Indicate at what step in the glycolysis pathway each of the following events occurs. a. b. c. d.

First phosphorylation of ADP occurs First “energy-rich” compound is produced Second “energy-rich” compound undergoes reaction First isomerization reaction occurs

Solution

a. Phosphorylation of ADP produces ATP with the added phosphate coming from a glycolysis intermediate. This process occurs for the first time in Step 7, where 1,3-bisphosphoglycerate is converted to 3-phosphoglycerate. It occurs a second time in Step 10. b. In carbohydrate metabolism, an “energy-rich” compound is a high-energy phosphate. Two such compounds are produced during glycolysis, the first in Step 6 and the second in Step 9. The Step 6 compound is 1,3-bisphosphoglycerate. c. The second “energy-rich” compound is phosphoenolpyruvate, which is produced in Step 9 and undergoes reaction in Step 10. (continued) (continued)

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d. There are three isomerization reactions in glycolysis. They occur in Steps 2, 5, and 8. In the first occurrence, Step 2, glucose 6-phosphate is converted to fructose 6-phosphate. Glucose and fructose are isomeric hexose (Section 18.8) molecules.

Practice Exercise 24.3 Indicate at what step in the glycolysis pathway each of the following events occurs. a. b. c. d.

Second formation of ATP occurs. Second “energy-rich” compound is produced. Second time ATP is converted to ADP. A dehydration reaction occurs.

Answers: a. Step 10; b. Step 9; c. Step 3; d. Step 9

EXAMPLE 24.4 Relating Enzyme Names and Functions to Steps in the Process of Glycolysis

Relate the names and functions of the following glycolytic enzymes to steps in the process of glycolysis. a. b. c. d.

Phosphofructokinase Phosphoglyceromutase Triosephosphate isomerase Enolase

Solution

a. A kinase is an enzyme that is involved with phosphate group transfer. The phosphofructo portion of the enzyme name refers to a fructose phosphate. Transfer of a phosphate group to a fructose phosphate occurs in Step 3. Fructose 6-phosphate is converted to fructose 1,6-bisphosphate. b. A mutase is an enzyme that shifts the position of a functional group within a molecule. Such a functional group shift occurs in Step 8, where 3-phosphoglycerate is isomerized to 2-phosphoglycerate. The phosphoglycero portion of the enzyme name indicates that a glycerate phosphate is the substrate for the enzyme. c. A triosephosphate isomerase effects the isomerization of a triose. Such a process occurs in Step 5, where dihydroxyacetone phosphate (a ketone) is converted to glyceraldehyde 3-phosphate (an aldehyde). Ketones and aldehydes with the same number of carbon atoms are often isomers. d. The only enol species in glycolysis is the compound phosphoenolpyruvate produced in Step 9 through a dehydration reaction that introduces a carbon–carbon double bond in the molecule. An enolase effects such a change.

Practice Exercise 24.4 Relate the names and functions of the following glycolytic enzymes to steps in the process of glycolysis. a. b. c. d.

Hexokinase Pyruvate kinase Glyceraldehyde 3-phosphate dehydrogenase Phosphoglycerokinase

Answers: a. Step 1; b. Step 10; c. Step 6; d. Step 7

Entry of Galactose and Fructose into Glycolysis The breakdown products from carbohydrate digestion are glucose, fructose, and galactose (Section 24.1). Both fructose and galactose are converted, in the liver, to intermediates that enter into the glycolysis pathway.

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Glucose

ATP Step 1 ADP Four steps

Galactose

ATP

Glucose 1-phosphate

Glucose 6-phosphate

Step 2

ADP

Fructose 6-phosphate

ATP Step 3 ADP Fructose 1,6-bisphosphate

Step 4

Step 5 Dihydroxyacetone phosphate Fructose

Fructose 1-phosphate

ADP ATP

ATP

ADP

Two glyceraldehyde 3-phosphates

Glyceraldehyde

2 NAD+ + 2 Pi Step 6

2 NADH + 2 H+

Two 1,3-bisphosphoglycerates

2 H2O Steps 7–10

4 ADP 4 ATP

Two pyruvates

Figure 24.5 Entry points for fructose and galactose into the glycolysis pathway.

The entry of fructose into the glycolytic pathway involves phosphorylation by ATP to produce fructose 1-phosphate, which is then split into two trioses—glyceraldehyde and dihydroxyacetone phosphate. Dihydroxyacetone phosphate enters glycolysis directly; glyceraldehyde must be phosphorylated by ATP to glyceraldehyde 3-phosphate before it enters the pathway (see Figure 24.5). The entry of galactose into the glycolytic pathway begins with its conversion to glucose 1-phosphate (a four-step sequence), which is then converted to glucose 6-phosphate, a glycolysis intermediate (see Figure 24.5).

Regulation of Glycolysis Glycolysis, like all metabolic pathways, must have control mechanisms associated with it. In glycolysis, the control points are Steps 1, 3, and 10 (see Figure 24.3). Step 1, the conversion of glucose to glucose 6-phosphate, involves the enzyme hexokinase. This particular enzyme is inhibited by glucose 6-phosphate, the substance produced by its action (feedback inhibition; Section 21.8).

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At Step 3, where fructose 6-phosphate is converted to fructose 1,6-bisphosphate by the enzyme phosphofructokinase, high concentrations of ATP and citrate inhibit enzyme activity. A high ATP concentration, which is characteristic of a state of low energy consumption, thus stops glycolysis at the fructose 6-phosphate stage. This stoppage also causes increases in glucose 6-phosphate stores because glucose 6-phosphate is in equilibrium with fructose 6-phosphate. The third control point involves the last step of glycolysis, the conversion of phosphoenolpyruvate to pyruvate. Pyruvate kinase, the enzyme needed at this point, is inhibited by high ATP concentrations. Both pyruvate kinase (Step 10) and phosphofructokinase (Step 3) are allosteric enzymes (Section 21.8).

24.3 FATES OF PYRUVATE The production of pyruvate from glucose (glycolysis) occurs in a similar manner in most cells. In contrast, the fate of the pyruvate so produced varies with cellular conditions and the nature of the organism. Three common fates for pyruvate are of prime importance: conversion into acetyl CoA, into lactate, and into ethanol (see Figure 24.6). A key concept in considering these fates of pyruvate is the need for a continuous supply of NAD for glycolysis. As glucose is oxidized to pyruvate in glycolysis, NAD is reduced to NADH. Glucose  2NAD

2 pyruvate  2NADH  2H 2ADP  2Pi

2ATP

It is significant that each pathway of pyruvate metabolism includes provisions for regeneration of NAD from NADH so that glycolysis can continue.

Oxidation to Acetyl CoA Under aerobic (oxygen-rich) conditions, pyruvate is oxidized to acetyl CoA. Pyruvate formed in the cytosol through glycolysis crosses the two mitochondrial membranes and enters the mitochondrial matrix, where the oxidation takes place. The overall reaction, in simplified terms, is O B CH3 O C O COO  CoAOSH  NAD

Pyruvate dehydrogenase complex

O B CH3 O C OSO CoA  NADH  CO2

Pyruvate

Acetyl CoA

Figure 24.6 The three common fates of pyruvate generated by glycolysis.

PYRUVATE O CH3

B

F

An additional fate for pyruvate is conversion to oxaloacetate. This fate for pyruvate, which occurs during the process called gluconeogenesis, is discussed in Section 24.6.

C

COO–

Aerobic conditions in humans, animals, and microorganisms

Anaerobic conditions in humans, animals, and some microorganisms

Anaerobic conditions in some microorganisms

ACETYL CoA

LACTATE

ETHANOL

O CH3

C

OH CoA + CO2

CH3

CH

COO–

CH3

CH2

OH + CO2

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24.3 Fates of Pyruvate

B

F

Not all acetyl CoA produced from pyruvate enters the citric acid cycle. Particularly when high levels of acetyl CoA are produced (from excess ingestion of dietary carbohydrates), some acetyl CoA is used as the starting material for the production of the fatty acids needed for fat (triacylglycerol) formation (Section 25.7).

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This reaction, which involves both oxidation and decarboxylation (CO2 is produced), is far more complex than the simple stoichiometry of the equation suggests. The enzyme complex involved contains three different enzymes, each with numerous subunits. The overall reaction process involves four separate steps and requires NAD, CoA—SH, FAD, and two other coenzymes (lipoic acid and thiamine pyrophosphate, the latter derived from the B vitamin thiamine). Most acetyl CoA molecules produced from pyruvate enter the citric acid cycle. Citric acid cycle operations change more NAD to its reduced form, NADH. The NADH from glycolysis, from the conversion of pyruvate to acetyl CoA, and from the citric acid cycle enters the electron transport chain directly (Section 23.7) or indirectly (Section 24.4). In the ETC, electrons from NADH are transferred to O2, and the NADH is changed back to NAD. The NAD needed for glycolysis, pyruvate–acetyl CoA conversion, and the citric acid cycle is regenerated. The net overall reaction for processing one glucose molecule to two molecules of acetyl CoA is Glucose  2ADP  2Pi  4NAD  2CoA OSH 2 acetyl CoA  2CO2  2ATP  4NADH  4H  2H2O

Fermentation Processes When the body becomes oxygen deficient (anaerobic conditions), such as during strenuous exercise, the electron transport chain process slows down because its last step is dependent on oxygen. The result of this “slowing down” is a buildup in NADH concentration (it is not being consumed so fast) and a decreased amount of available NAD (it is not being produced so fast). Decreased NAD concentration then negatively affects the rate of glycolysis. An alternative method for conversion of NADH to NAD—a method that does not require oxygen—is needed if glycolysis is to continue, it being the only available source of new ATP under these conditions. Fermentation processes solve this problem. Fermentation is a biochemical process by which NADH is oxidized to NAD without the need for oxygen. We consider here two fermentation processes: lactate fermentation and ethanol fermentation.

Lactate Fermentation Lactate fermentation is the enzymatic anaerobic reduction of pyruvate to lactate. The sole purpose of this process is the conversion of NADH to NAD. The lactate so formed is converted back to pyruvate when aerobic conditions are again established in a cell (Section 24.6). Working muscles often produce lactate. If strenuous exercise is continued too long, the buildup of lactate in the muscles reaches a point beyond which fermentation cannot continue. This slows glycolysis and new ATP production, and the muscle action can no longer continue (fatigue and exhaustion; see the accompanying Chemical Connections feature on page 825) until oxygen supplies are re-established. The equation for lactate formation from pyruvate is O B CH3 O C O COO  NAD H  H Pyruvate

Red blood cells have no mitochondria and therefore always form lactate as the end product of glycolysis.

Lactate dehydrogenase

OH A CH3 O C H O COO  NAD Lactate

When the reaction for conversion of pyruvate to lactate is added to the net glycolysis reaction (Section 24.2), an overall reaction for the conversion of glucose to lactate is obtained. Glucose  2ADP  2Pi

2 lactate  2ATP  2H2O

Note that NADH and NAD do not appear in this equation, even though the process cannot proceed without them. The NADH generated during glycolysis (Step 6) is consumed

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in the conversion of pyruvate to lactate. Thus there is no net oxidation–reduction in the conversion of glucose to lactate.

Ethanol Fermentation With bread and other related products obtained using yeast, the ethanol produced by fermentation evaporates during baking.

Under anaerobic conditions, several simple organisms, including yeast, possess the ability to regenerate NAD through ethanol, rather than lactate, production. Such a process is called ethanol fermentation. Ethanol fermentation is the enzymatic anaerobic conversion of pyruvate to ethanol and carbon dioxide. Ethanol fermentation involving yeast causes bread and related products to rise as a result of CO2 bubbles being released during baking. Beer, wine, and other alcoholic drinks are produced by ethanol fermentation of the sugars in grain and fruit products. The first step in conversion of pyruvate to ethanol is a decarboxylation reaction to produce acetaldehyde. O B CH3 O C O COO  H Pyruvate

Pyruvate decarboxylase

O B CH3 O C O H  CO2 Acetaldehyde

The second step involves acetaldehyde reduction to produce ethanol. O B CH3 O C O H  NAD H  H

OH A CH3 O CO H  NAD A H

Alcohol dehydrogenase

Acetaldehyde

Ethanol

The overall equation for the conversion of pyruvate to ethanol (the sum of the two steps) is O B CH3 O C O COO  2H  NADH

Two steps

CH3 OCH C 2OOH  NAD  CO2

Pyruvate

Ethanol

An overall reaction for the production of ethanol from glucose is obtained by combining the reaction for the conversion of pyruvate with the net reaction for glycolysis (Section 24.2). Glucose  2ADP  2Pi

2 ethanol  2CO2  2ATP  2H2O

Again note that NADH and NAD do not appear in the final equation; they are both generated and consumed. Figure 24.7 summarizes the relationship between the fates of pyruvate and the regeneration of NAD from NADH.

Figure 24.7 All three of the

NAD+

Pyruvate

common fates of pyruvate from glycolysis provide for the regeneration of NAD from NADH.

NADH

NADH NAD+

CO2 Acetaldehyde

Lactate

CO2 Acetyl CoA NAD+

NADH Citric acid cycle NAD+ Ethanol

Electron transport chain

NADH NADH NAD+

Further oxidation

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24.3 Fates of Pyruvate

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HEMICAL

onnections

Lactate Accumulation

During strenuous exercise, conditions in muscle cells can change from aerobic to anaerobic as the oxygen supply becomes inadequate to meet demand. Such conditions cause pyruvate to be converted to lactate rather than acetyl CoA. (Lactate production can also be high at the start of strenuous exercise before the delivery of oxygen is stepped up via an increased respiration rate.) The resulting lactate begins to accumulate in the cytosol of cells where it is produced. Some lactate diffuses out of the cells into the blood, where it contributes to a slight decrease in blood pH. This lower pH triggers fast breathing, which helps supply more oxygen to the cells. Lactate accumulation is the cause of muscle pain and cramping during prolonged, strenuous exercise. As a result of such cramping, muscles may be stiff and sore the next day. Regular, hard exercise increases the efficiency with which oxygen is delivered to the body. Thus athletes can function longer than nonathletes under aerobic conditions without lactate production. Lactate accumulation can also occur in heart muscle if it experiences decreased oxygen supply (from artery blockage). The heart muscle experiences cramps and stops beating (cardiac arrest). Massage of heart muscle often reduces such cramps, just as it does for skeletal muscle, and it is sometimes possible to start the heart beating again by using such a technique. Premature infants born with underdeveloped lungs are often given increased amounts of oxygen to minimize lactate accumulation. They are also given bicarbonate (HCO3) solution to counteract the acidity change in blood that accompanies lactate buildup. Rapid breathing, which is also called hyperventilation, raises slightly the pH of blood. The CO2 loss associated with the rapid breathing causes carbonic acid (H2CO3) present in the blood to dissociate in CO2 and H2O to replace the lost CO2. H2CO3 Δ CO2  H2O

E X A M P L E 24. 5 Identifying Characteristics of the Three Common Pathways by Which Pyruvate Is Converted to Other Products

A decreased amount of carbonic acid causes blood pH to rise, which makes the blood slightly more basic. Athletes who compete in short-distance races, such as 50 meters and 100 meters, have learned how to use this phenomenon of hyperventilation to their advantage. A few seconds before the start of the race, through hyperventilation, they decrease the amount of CO2 in their lungs, making their blood a little bit more basic. This slight increase in basicity means the runner can absorb slightly more lactic acid before the blood pH drops to the point where cramping becomes a problem. Having such an advantage for only a few seconds in a short race can be helpful.

Strenuous muscular activity can result in lactate accumulation.

Which of the three common metabolic pathways for pyruvate is compatible with each of the following characterizations concerning the reactions that pyruvate undergoes? a. b. c. d.

CO2 is not a product for this pathway. A C3 molecule is a product for this pathway. NAD is needed as an oxidizing agent for this pathway. A C2 molecule is a product under anaerobic reaction conditions for this pathway.

Solution

a. CO2 is a product for both acetyl CoA formation and ethanol fermentation. In both of these processes the C3 pyruvate is converted to a C2 species and CO2. No CO2 production occurs during lactate fermentation, as C3 pyruvate is converted to C3 lactate. b. The only pathway that produces a C3 molecule is lactate fermentation. In the other two pathways a C2 molecule and CO2 are produced. c. NAD, as an oxidizing agent, is needed in pathways that function under aerobic conditions. NADH, as a reducing agent, is needed in pathways that function under anaerobic conditions. The only pathway that involves aerobic conditions is acetyl CoA formation. d. Alcohol fermentation, an anaerobic process, produces ethanol, a C2 molecule. The other anaerobic process, lactate fermentation, produces the C3 molecule lactate. (continued)

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Practice Exercise 24.5 Which of the three common metabolic pathways for pyruvate is compatible with each of the following characterizations concerning the reactions that pyruvate undergoes? a. b. c. d.

Acetaldehyde is an intermediate in this pathway. An anaerobic pathway that does not function in humans. An anaerobic pathway that does function in humans. A C2 molecule is a product under aerobic reaction conditions for this pathway.

Answers: a. Ethanol fermentation; b. Ethanol fermentation; c. Lactate fermentation; d. Acetyl CoA formation

24.4 ATP PRODUCTION FOR THE COMPLETE OXIDATION OF GLUCOSE We now assemble energy production figures for glycolysis, oxidation of pyruvate to acetyl CoA, the citric acid cycle, and the electron transport chain. The result, with one added piece of information, gives the ATP yield for the complete oxidation of one molecule of glucose. The new piece of information involves the NADH produced during Step 6 of glycolysis. This NADH, produced in the cytosol, cannot directly participate in the electron transport chain because mitochondria are impermeable to NADH (and NAD). A transport system shuttles the electrons from NADH, but not NADH itself, across the membrane. This shuttle involves dihydroxyacetone phosphate (a glycolysis intermediate) and glycerol 3-phosphate. The first step in the shuttle is the cytosolic reduction of dihydroxyacetone phosphate by NADH to produce glycerol 3-phosphate and NAD (see Figure 24.8). Glycerol 3-phosphate then crosses the outer mitochondrial membrane, where it is reoxidized to dihydroxyacetone phosphate. The oxidizing agent is FAD rather than NAD. The regenerated dihydroxyacetone phosphate diffuses out of the mitochondrion and returns to the cytosol for participation in another “turn” of the shuttle. The FADH2 coproduced in the mitochondrial reaction can participate in the electron transport chain reactions. The net reaction of this shuttle process is

Figure 24.8 The dihydroxyacetone phosphate–glycerol 3-phosphate shuttle.

Dihydroxyacetone phosphate

Glycerol 3-phosphate

+

NADH + H

CH2OH

Cytosol

C

O

CH2OPO3

Outer mitochondrial membrane

CH2OH

NAD+ HO 2–

–

Diffuses into mitochondrion

Diffuses into cytoplasm

C

CH2OH

O

– CH2OPO32

Inner mitochondrial membrane

H

CH2OPO32

CH2OH

Mitochondrial intermembrane space

C

HO FADH2

C

H

CH2OPO32 FAD

–

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24.4 ATP Production for the Complete Oxidation of Glucose

TABLE 24.2 Production of ATP from the Complete Oxidation of One Glucose Molecule in a Skeletal Muscle Cell Reaction

Comments

Yield of ATP

Glycolysis

glucose n glucose 6-phosphate glucose 6-phosphate n fructose 1,6-bisphosphate 2(glyceraldehyde 3-phosphate n 1,3-bisphosphoglycerate) 2(1,3-bisphosphoglycerate n 3-phosphoglycerate) 2(phosphoenolpyruvate n pyruvate)

⫺1 ⫺1 — ⫹2 ⫹2

consumes 1 ATP consumes 1 ATP each produces 1 cytosolic NADH each produces 1 ATP each produces 1 ATP

Oxidation of Pyruvate

2(pyruvate n acetyl CoA ⫹ CO2)

each produces 1 NADH

—

each produces 1 NADH each produces 1 NADH each produces 1 GTP each produces 1 FADH2 each produces 1 NADH

— — ⫹2 — —

each produces 1.5 ATP each produces 2.5 ATP each produces 1.5 ATP each produces 2.5 ATP

⫹3 ⫹5 ⫹3 ⫹15

Citric Acid Cycle

2(isocitrate n ␣-ketoglutarate ⫹ CO2) 2(␣-ketoglutarate n succinyl CoA ⫹ CO2) 2(succinyl CoA n succinate) 2(succinate n fumarate) 2(malate n oxaloacetate) Electron Transport Chain and Oxidative Phosphorylation

2 cytosolic NADH formed in glycolysis 2 NADH formed in the oxidation of pyruvate 2 FADH2 formed in the citric acid cycle 6 NADH formed in the citric acid cycle

⫹30

Net production of ATP

NADH ⫹ H⫹ ⫹ (cytosolic)

FAD

(mitochondrial)

¡ NAD ⫹ ⫹ FADH 2 (cytosolic)

(mitochondrial)

The consequence of this reaction is that only 1.5 rather than 2.5 molecules of ATP are formed for each cytosolic NADH, because FADH2 yields one less ATP than does NADH in the electron transport chain. Table 24.2 shows ATP production for the complete oxidation of a molecule of glucose. The final number is 30 ATP, 26 of which come from the oxidative phosphorylation associated with the electron transport chain. This total of 30 ATP for complete oxidation contrasts markedly with a total of 2 ATP for oxidation of glucose to lactate and 2 ATP for oxidation of glucose to ethanol. Neither of these latter processes involves the citric acid cycle or the electron transport chain. Thus the aerobic oxidation of glucose is 15 times more efficient in the production of ATP than the anaerobic lactate and ethanol processes. The production of 30 ATP molecules per glucose (Table 24.2) is for those cells where the dihydroxyacetone phosphate–glycerol 3-phosphate shuttle operates (skeletal muscle and nerve cells). In certain other cells, particularly heart and liver cells, a more complex shuttle system called the malate–aspartate shuttle functions. In this shuttle, 2.5 ATP molecules result from 1 cytosolic NADH, which changes the total ATP production to 32 molecules per glucose. The net overall reaction for the complete metabolism (oxidation) of a glucose molecule is the simple equation Glucose ⫹ 6O2 ⫹ 30ADP ⫹ 30Pi ¡ 6CO2 ⫹ 6H2O ⫹ 30 ATP Note that substances such as NADH, NAD⫹, and FADH2 are not part of this equation. Why? They cancel out—that is, they are consumed in one step (reactant) and regenerated in another step (product). Note also what the net equation does not acknowledge: the many dozens of reactions that are needed to generate the 30 molecules of ATP.

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Chapter 24 Carbohydrate Metabolism

24.5 GLYCOGEN SYNTHESIS AND DEGRADATION Glycogen, a branched polymeric form of glucose (Section 18.15), is the storage form of carbohydrates in humans and animals. It is found primarily in muscle and liver tissue. In muscles it is the source of glucose needed for glycolysis. In the liver, it is the source of glucose needed to maintain normal glucose levels in the blood.

Glycogenesis Glycogenesis is the metabolic pathway by which glycogen is synthesized from glucose 6-phosphate. Glycogenesis involves three reactions (steps). Formation of Glucose 1-phosphate. The starting material for this step is not glucose itself but rather glucose 6-phosphate (available from the first step of glycolysis). The enzyme phosphoglucomutase effects the change from a 6-phosphate to a 1-phosphate.

Step 1:

6

P O OOCH2

HO OCH2 Phosphoglucomutase

O

HO

OH

OH

O 1

HO

OH

O

OH

P

OH

Glucose 6-phosphate

Step 2:

O

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Glucose 1-phosphate

Formation of UDP-glucose. Glucose 1-phosphate from Step 1 must be activated before it can be added to a growing glycogen chain. The activator is the highenergy compound UTP (uridine triphosphate). A UMP is transferred to glucose 1-phosphate and the resulting PPi is hydrolyzed to 2Pi. O HN

CH2OH O

HO

OH

O B O O P O O A  O OH

O O O B B B O O P O OO P O O O P O O OCH2  A A A O O O

O

N UDP-glucose pyrophosphorylase

O

OH

OH

Uridine triphosphate (UTP)

Glucose 1-phosphate

O CH2OH O

HO

OH

HN

O O B B OO P OOO P OOO CH2 A A O O OH

O

N  PPi

O

H2O

2Pi OH Uridine diphosphate glucose (UDP-glucose)

OH

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24.5 Glycogen Synthesis and Degradation

Step 3:

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Glucose Transfer to a Glycogen Chain. The glucose unit of UDP-glucose is then attached to the end of a glycogen chain. UDP-glucose  (glucose)n

Glycogen synthase

Glycogen chain

(glucose)n1  UDP

Glycogen with an additional glucose unit

In a subsequent reaction, the UDP produced in Step 3 is converted back to UTP, which can then react with another glucose 1-phosphate (Step 2). The conversion reaction requires ATP. UDP  ATP 88n UTP  ADP Adding a single glucose unit to a growing glycogen chain requires the investment of two ATP molecules: one in the formation of glucose 6-phosphate and one in the regeneration of UTP.

Glycogenolysis Glycogenolysis is the metabolic pathway by which glucose 6-phosphate is produced from glycogen. This process is not simply the reverse of glycogen synthesis (glycogenesis), because it does not require UTP or UDP molecules. Glycogenolysis is a two-step process rather than a three-step process. Step 1: A phosphorylase is an enzyme that catalyzes the cleavage of a bond by Pi (in contrast to hydrolysis, which refers to bond cleavage by water), such as removal of a glucose unit from glycogen to give glucose 1-phosphate.

Phosphorylation of a Glucose Residue. The enzyme glycogen phosphorylase effects the removal of an end glucose unit from a glycogen molecule as glucose 1-phosphate.

(Glucose)n  Pi Glycogen

Step 2:

Glycogen Phosphorylase

(glucose)n1  glucose 1-phosphate

Glycogen with one fewer glucose unit

Glucose 1-phosphate Isomerization. The enzyme phosphoglucomutase catalyzes the isomerization process whereby the phosphate group of glucose 1-phosphate is moved to the carbon 6 position. Phosphoglucomutase

Glucose 1-phosphate Δglucose 6-phosphate A phosphatase is an enzyme that effects the removal of a phosphate group (Pi) from a molecule, such as converting glucose 6-phosphate to glucose, with H2O as the attacking species.

The fact that glycogen synthesis (glycogenesis) and glycogen degradation (glycogenolysis) are not totally reverse processes has significance. In fact, it is almost always the case in biochemistry that “opposite” biosynthetic and degradative pathways differ in some steps. This allows for separate control of the pathways.

This process is the reverse of the first step of glycogenesis. In muscle and brain cells an immediate need for energy is the stimulus that initiates glycogenolysis. The glucose 6-phosphate that is produced directly enters the glycolysis pathway at Step 1 (Figure 24.3) and its multistep conversion to pyruvate begins. A low level of glucose is the stimulus that initiates glycogenolysis in liver cells. Here, the glucose 6-phosphate produced must be converted to free glucose before it can enter the bloodstream, as glucose 6-phosphate cannot cross cell membranes (Section 24.2). This change is effected by the enzyme glucose 6-phosphatose, an enzyme found in liver cells but not in muscle cells or brain cells. Glucose 6-phosphate  H2O

Glucose 6-phosphatase

glucose  Pi

Because muscle and brain cells lack glucose 6-phosphatose, they cannot form free glucose from glucose 6-phosphate. Thus, muscle and brain cells can use glucose 6-phosphate from glycogen for energy production only. The liver, however, with this enzyme present, has the capacity to use glucose 6-phosphate obtained from glycogen to supply additional glucose to the blood. Figure 24.9 contrasts the “opposite” processes of glycogenesis and glycogenolysis. Both processes involve the glycolysis intermediate glucose 6-phosphate. UDP–glucose is unique to glycogenesis.

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Chapter 24 Carbohydrate Metabolism

GLYCOGENESIS (Glycogen)n PPi ATP

ADP

UTP UDP–Glucose

UTP

UDP–Glucose pyrophosphorylase

Hexokinase

Glucose 6-phosphate

Glucose Glucose 6-phosphatase

Glycolysis

Glucose 1-phosphate

Glycogen synthase

(Glycogen)n+1

Glycogen phosphorylase

Phosphoglucomutase

Pi

(Glycogen)n GLYCOGENOLYSIS

Figure 24.9 The processes of glycogenesis and glycogenolysis contrasted. The intermediate UDP—glucose is part of glycogenesis but not of glycogenolysis.

24.6 GLUCONEOGENESIS Gluconeogenesis is the metabolic pathway by which glucose is synthesized from noncarbohydrate materials. Glycogen stores in muscle and liver tissue are depleted within 12–18 hours from fasting or in even less time from heavy work or strenuous exercise. Without gluconeogenesis, the brain, which is dependent on glucose as a fuel, would have problems functioning if food intake were restricted for even one day. The noncarbohydrate starting materials for gluconeogenesis are lactate (from hardworking muscles and from red blood cells), glycerol (from triacylglycerol hydrolysis), and certain amino acids (from dietary protein hydrolysis or from muscle protein during starvation). About 90% of gluconeogenesis takes place in the liver. Hence gluconeogenesis helps to maintain normal blood-glucose levels in times of inadequate dietary carbohydrate intake (such as between meals). The processes of gluconeogenesis (pyruvate to glucose) and glycolysis (glucose to pyruvate) are not exact opposites. The most obvious difference between these two processes is that 12 compounds are involved in gluconeogenesis and only 11 in glycolysis. Why the difference? The last step of glycolysis is the conversion of the high-energy compound phosphoenolpyruvate to pyruvate. The reverse of this process, which is the beginning of gluconeogenesis, cannot be accomplished in a single step because of the large energy difference between the two compounds and the slow rate of the reaction. Instead, a two-step process by way of oxaloacetate is required to effect the change, and this adds an extra compound to the gluconeogenesis pathway (see Figure 24.10). Both an ATP molecule and a GTP molecule are needed to drive this two-step process.

Figure 24.10 The “opposite” processes of gluconeogenesis (pyruvate to glucose) and glycolysis (glucose to pyruvate) are not exact opposites. The reversal of the last step of glycolysis requires two steps in gluconeogenesis. Therefore, gluconeogenesis has 11 steps, whereas glycolysis has only 10 steps.

Phosphoenolpyruvate

Last step of glycolysis

Pyruvate kinase

Phosphoenolpyruvate carboxykinase

Oxaloacetate

Pyruvate

Pyruvate carboxylase

First two steps of gluconeogenesis

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24.6 Gluconeogenesis

COO A C P O  CO2  ATP  H2O A CH3

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COO A C P O  ADP  Pi A CH2 A COO

Pyruvate carboxylase Biotin

Pyruvate

Oxaloacetate

COO A CPO A  GTP CH2 A  COO

Phosphoenolpyruvate carboxykinase

Oxaloacetate

Glycolysis has a net production of 2 ATP (Section 24.2). Gluconeogenesis has a net expenditure of 4 ATP and 2 GTP, which is equivalent to the expenditure of 6 ATP.

2 Pyruvate  4ATP  2GTP  2NADH  2H2O glucose  4ADP  2GDP  6Pi  2NAD

Figure 24.11 The pathway for

Glucose

gluconeogenesis is similar, but not identical, to the pathway for glycolysis.

Hexokinase (ATP required)

Glucose 6-phosphatase (no ATP required)

Glucose 6-phosphate

Fructose 6-phosphate Phosphofructokinase (ATP required)

Fructose 1,6-bisphosphatase (no ATP required)

Fructose 1,6-bisphosphate

Phosphoenolpyruvate

Pyruvate kinase (no ATP required)

Phosphoenolpyruvate carboxykinase (GTP required)

Oxaloacetate Pyruvate carboxylase (ATP and CO2 required)

Pyruvate

GLUCONEOGENESIS

F

Phosphoenolpyruvate

The oxaloacetate intermediate in this two-step process provides a connection to the citric acid cycle. In the first step of this cycle, oxaloacetate combines with acetyl CoA. If energy rather than glucose is needed, then oxaloacetate can go directly into the citric acid cycle. As is shown in Figure 24.11, there are two other locations where gluconeogenesis and glycolysis differ. In Steps 9 and 11 of gluconeogenesis (Steps 1 and 3 of glycolysis), the reactant–product combinations match between pathways. However, different enzymes are required for the forward and reverse processes. The new enzymes for gluconeogenesis are fructose 1,6-bisphosphatase and glucose 6-phosphatase. The overall net reaction for gluconeogenesis is

GLYCOLYSIS

B

O O M D C A C OOO P  CO2  GDP B CH2

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Chapter 24 Carbohydrate Metabolism

Figure 24.12 The Cori cycle. Lactate, formed from glucose under anaerobic conditions in muscle cells, is transferred to the liver, where it is reconverted to glucose, which is then transferred back to the muscle cells.

Glucose GLYCOLYSIS Pyruvate

Glucose Active skeletal muscle

Lactate

GLUCONEOGENESIS Liver Pyruvate

Lactate

Thus to reconvert pyruvate to glucose requires the expenditure of 4 ATP and 2 GTP. Whenever gluconeogenesis occurs, it is at the expense of other ATP-producing metabolic processes.

The Cori Cycle The Cori cycle is named in honor of Gerty Radnitz Cori (1896–1957) and Carl Cori (1896–1984), the husbandand-wife team who discovered it. They were awarded a Nobel Prize in 1947, the third husband-and-wife team to be so recognized. Marie and Pierre Curie were the first, Irene and Frederic Joliot-Curie the second.

Gluconeogenesis using lactate as a source of pyruvate is particularly important because of lactate formation during strenuous exercise. The lactate so produced (Section 24.3) diffuses from muscle cells into the blood, where it is transported to the liver. Here the enzyme lactate dehydrogenase (the same enzyme that catalyzes lactate formation in muscle) converts lactate back to pyruvate. COO A H OC O O H  NAD A CH3 Lactate

Lactate dehydrogenase

COO A C P O  NAD H  H A CH3 Pyruvate

The newly formed pyruvate is then converted via gluconeogenesis to glucose, which enters the bloodstream and goes to the muscles. This cyclic process, which is called the Cori cycle, is diagrammed in Figure 24.12. The Cori cycle is a cyclic biochemical process in which glucose is converted to lactate in muscle tissue, the lactate is reconverted to glucose in the liver, and the glucose is returned to the muscle tissue.

24.7 TERMINOLOGY FOR GLUCOSE METABOLIC PATHWAYS In the preceding three sections we considered the processes of glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis. Because of their like-sounding names, keeping the terminology for these four processes “straight” is often a problem. Figure 24.13 shows the relationships among these processes. Note that the glycogen degradation pathways (left side of Figure 24.13) have names ending in -lysis, which means “breakdown.” The pathways associated with glycogen synthesis (right side of Figure 24.13) have names ending in -genesis, which means “making.”

EXAMPLE 24.6 Recognizing Characteristics of Glycolysis, Glycogenesis, Glycogenolysis, and Gluconeogenesis

Identify each of the following as a characteristic of one or more of the following processes: glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis. a. b. c. d.

Glucose 6-phosphate is the initial reactant. Glucose is the final product. Glucose 6-phosphate is produced in the first step. UTP is involved in this process.

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24.8 The Pentose Phosphate Pathway

Figure 24.13 The relationships

833

Glycogen

among four common metabolic pathways that involve glucose.

GLYCOGENOLYSIS

GLYCOGENESIS

Glucose 6-phosphate

Glucose 6-phosphate

Glucose

GLYCOLYSIS

Glucose

GLUCONEOGENESIS Pyruvate

Lactate

Acetyl CoA

Ethanol

Solution

a. Glycogenesis. In this 3-step process glucose 6-phosphate units are added to a growing glycogen molecule. b. Gluconeogenesis. This 11-step process converts pyruvate into glucose. c. Glycolysis. The first step of glycolysis is the production of glucose 6-phosphate from glucose. The glucose 6-phosphate produced can then be further processed in the glycolysis pathway or processed to glycogen using the glycogenesis pathway. d. Glycogenesis. The second step of glycogenesis is the conversion of glucose 1-phosphate to UDP-glucose.

Practice Exercise 24.6 Identify each of the following as a characteristic of one or more of the following processes: glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis. a. b. c. d.

Glycogen is the final product. Glucose is the initial reactant. Glucose 1-phosphate is produced in the first step. ADP is converted to ATP in this process.

Answers: a. Glycogenesis; b. Glycolysis; c. Glycogenesis; d. Glycolysis

24.8 THE PENTOSE PHOSPHATE PATHWAY Glycolysis is not the only pathway by which glucose may be degraded. Depending on the type of cell, various amounts of glucose are degraded by the pentose phosphate pathway, a pathway whose main focus is not subsequent ATP production as is the case for glycolysis. Major functions of this alternative pathway are (1) synthesis of the coenzyme NADPH needed in lipid biosynthesis (Section 25.7), and (2) production of ribose 5-phosphate, a pentose derivative needed for the synthesis of nucleic acids and many coenzymes. The pentose phosphate pathway is the metabolic pathway by which glucose is used to produce NADPH, ribose 5-phosphate (a pentose phosphate), and numerous other sugar phosphates. The operation of the pentose phosphate pathway is significant in cells that produce lipids: fatty tissue, the liver, mammary glands, and the adrenal cortex (an active producer of steroid lipids).

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Chapter 24 Carbohydrate Metabolism

H H

O C

H2N O –

O

P

N O

O

CH2

OH O

OH

NH2 N

N

O

P

O

6

P OO O CH2 O

N

N –

NADPH, the coenzyme produced in the pentose phosphate pathway, is the reduced form of NADP⫹ (nicotinamide adenine dinucleotide phosphate). Structurally, NADP⫹/ NADPH is a phosphorylated version of NAD⫹/NADH (see Figure 24.14). The nonphosphorylated and phosphorylated versions of this coenzyme have significantly different functions. The nonphosphorylated version is involved, mainly in its oxidized form (NAD⫹), in the reactions of the common metabolic pathway (Section 23.5). The phosphorylated version is involved, mainly in its reduced form (NADPH), in biosynthetic reactions of lipids and nucleic acids. There are two stages within the pentose phosphate pathway—an oxidative stage and a nonoxidative stage. The oxidative stage, which occurs first, involves three steps through which glucose 6-phosphate is converted to ribulose 5-phosphate and CO2.

O

CH2

HO

O

Three steps

OH

OH

2NADP⫹

2NADPH/2H⫹

OH OH –

O

Glucose 6-phosphate

O O

P –

O

Figure 24.14 The Structure of NADPH. The phosphate group shown in color is the structural feature that distinguishes NADPH from NADH.

CH2OH A C PO A ⫹ CO2 H O COOH A H O CO OH A CH2 O O O P Ribulose 5-phosphate

The net equation for the oxidative stage of the pentose phosphate pathway is Glucose 6-phosphate ⫹ 2NADP⫹ ⫹ H2O ¡ ribulose 5-phosphate ⫹ CO2 ⫹ 2NADPH ⫹ 2H⫹ Note the production of two NADPH molecules per glucose 6-phosphate processed during this stage. In the first step of the nonoxidative stage of the pentose phosphate pathway, ribulose 5-phosphate (a ketose) is isomerized to ribose 5-phosphate (an aldose). H

CH2OH A CP O A H O COOH A H O CO OH A CH2 O O O P Ribulose 5-phosphate

Phosphopentose isomerase

G KO C A H O C OOH A H O COOH A H O CO OH A CH2 O O O P Ribose 5-phosphate

The pentose ribose is a component of ATP, GTP, UTP, CoA, NAD⫹/NADH, FAD/FADH2, and RNA. Further steps in the nonoxidative stage contain provision for the conversion of ribose 5-phosphate to numerous other sugar phosphates. Ultimately, glyceraldehyde 3-phosphate and fructose 6-phosphate (both glycolysis intermediates) are formed. The overall net reaction for the pentose phosphate pathway is 3 Glucose 6-phosphate ⫹ 6NADP⫹ ⫹ 3H2O ¡ 2 fructose 6-phosphate ⫹ 3CO2 ⫹ glyceraldehyde 3-phosphate ⫹ 6NADPH ⫹ 6H⫹ The pentose phosphate pathway, with its many intermediates, helps meet cellular needs in numerous ways. 1. When ATP demand is high, the pathway continues to its end products, which enter glycolysis. 2. When NADPH demand is high, intermediates are recycled to glucose 6-phosphate (the start of the pathway), and further NADPH is produced. 3. When ribose 5-phosphate demand is high, for nucleic acid and coenzyme production, most of the nonoxidative stage is nonfunctional, leaving ribose 5-phosphate as a major product.

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24.9 Hormonal Control of Carbohydrate Metabolism

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Glucose Metabolism Carbohydrates from food intake

DIGESTION

GLYCOGENOLYSIS

Pentoses + CO2

Pentose phosphate pathway Glucose

Glycogen Glucose 6-phosphate – 2 ATP

GLYCOGENESIS GLUCONEOGENESIS GLYCOLYSIS

– 6 ATP

+ 2 ATP

Pyruvate

Lactate CO2

Acetyl CoA

CITRIC ACID CYCLE

CO2

+ 2 ATP H2O

ELECTRON TRANSPORT CHAIN

+ 26 ATP

The Chemistry at a Glance feature above shows how the pentose phosphate pathway is related to the other major pathways of glucose metabolism that we have considered.

24.9 HORMONAL CONTROL OF CARBOHYDRATE METABOLISM A second major method for regulating carbohydrate metabolism, besides enzyme inhibition by metabolites (Section 24.2), is hormonal control. Among others, three hormones—insulin, glucagon, and epinephrine—affect carbohydrate metabolism.

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c

HEMICAL

Diabetes Mellitus

Diabetes mellitus is the best-known and most prevalent metabolic disease in humans, affecting approximately 4% of the population. There are two major forms of this disease: insulin-dependent (type I) and non–insulin-dependent (type II) diabetes. Type I diabetes, which often appears in children, is the result of inadequate insulin production by the beta cells of the pancreas. Control of this condition involves insulin injections and special dietary programs. A risk associated with the insulin injections is that too much insulin can produce severe hypoglycemia (insulin shock); blackout or a coma can result. Treatment involves a quick infusion of glucose. Diabetics often carry candy bars (quick glucose sources) for use if they feel any of the symptoms that signal the onset of insulin shock. In Type II diabetes, which usually occurs in overweight individuals more than 40 years old, body insulin production can be normal, but the cells do not respond to it normally. Some of the insulin receptors on the cell membranes are not functioning properly and fail to recognize the insulin. Treatment involves drugs that increase body insulin levels and a carefully regulated diet (to reduce obesity). More efficient use of undamaged receptors occurs at increased insulin levels. About 10% of all cases of diabetes are type I. The more common non–insulin-dependent type II diabetes occurs in the other 90% of cases. The effects of both types of diabetes are the same—inadequate glucose uptake by cells. The result is bloodglucose levels much higher than normal (hyperglycemia). With an inadequate glucose intake, cells must resort to other procedures for energy production, procedures that involve the breakdown of fats and protein. Insulin was discovered in 1921, the first human body hormone to be discovered. Since that time, researchers have been searching for noninvasive (needle-free) ways to deliver the hormone to people who have diabetes. Avenues that have been investigated include oral delivery, nasal delivery, and dermal delivery using a patch. The first approval of a noninvasive approach to insulin therapy was given by the U.S. Food and Drug Administration

Severe diabetes Blood-glucose level (mg/100 mL)

onnections

300

Mild diabetes 200

100 Normal

0.5

1 2 3 Time (hours) Typical Tolerance Curves for Glucose

in 2006. It involves inhalable insulin, delivered with an inhaler, much the same way medicine to treat asthma is delivered. The insulin can be packaged as a powder or liquid. Tests show that inhalable insulin is as effective as injections in controlling blood sugar. The inhalable insulin reaches the deep lung alveoli structures, which offer the largest surface area for absorption. A concern about inhalable insulin is its cost, which is three to four times more than injectable insulin. It is still an important development for people who sometimes refuse insulin treatment because of a fear of needles. Another concern is convenience. The inhaler used to dispense the insulin is about 6 inches long (the size of an eyeglass case) when stored and about a foot long when it is in use.

Insulin Insulin, a 51-amino-acid protein whose structure we considered in Section 20.11, is a hormone produced by the beta cells of the pancreas. Insulin promotes the uptake and utilization of glucose by cells. Thus its function is to lower blood glucose levels. It is also involved in lipid metabolism. The release of insulin is triggered by high blood-glucose levels. The mechanism for insulin action involves insulin binding to protein receptors on the outer surfaces of cells, which facilitates entry of glucose into the cells. Insulin also produces an increase in the rates of glycogen synthesis, glycolysis, and fatty acid synthesis.

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Concepts to Remember

Figure 24.15 The series of events by which the hormone epinephrine stimulates glucose production.

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Epinephrine (first messenger) Adenyl cyclase Receptor site

Glucose 6-phosphate

ATP Glycogen

Cell membrane

Cyclic AMP (second messenger)

Glycogen phosphorylase

Glucagon Glucagon is a polypeptide hormone (29 amino acids) produced in the pancreas by alpha cells. It is released when blood-glucose levels are low. Its principal function is to increase blood-glucose concentrations by speeding up the conversion of glycogen to glucose (glycogenolysis) and gluconeogenesis in the liver. Thus glucagon’s effects are opposite to those of insulin.

Epinephrine Epinephrine (Section 17.10), also called adrenaline, is released by the adrenal glands in response to anger, fear, or excitement. Its function is similar to that of glucagon—stimulation of glycogenolysis, the release of glucose from glycogen. Its primary target is muscle cells, where energy is needed for quick action. It also functions in lipid metabolism. Epinephrine acts by binding to a receptor site on the outside of the cell membrane, stimulating the enzyme adenyl cyclase to begin production of a second messenger, cyclic AMP (cAMP) from ATP. The cAMP is released in the cell interior, where, in a series of reactions, it activates glycogen phosphorylase, the enzyme that initiates glycogenolysis. The glucose 6-phosphate that is produced from the glycogen breakdown provides a source of quick energy. Figure 24.15 shows the series of events initiated by the release of the hormone epinephrine. Cyclic AMP also inhibits glycogenesis, thus preventing glycogen production at the same time.

c

O N C E P TS TO R E M E M B E R

Glycolysis. Glycolysis, a series of ten reactions that occur in the cytosol, is a process in which one glucose molecule is converted into two molecules of pyruvate. A net gain of two molecules of ATP and two molecules of NADH results from the metabolizing of glucose to pyruvate (Section 24.2). Fates of pyruvate. With respect to energy-yielding metabolism, the pyruvate produced by glycolysis can be converted to acetyl CoA under aerobic conditions or to lactate under anaerobic conditions. Some microorganisms convert pyruvate to ethanol, an anaerobic process (Section 24.3). Glycogenesis. Glycogenesis is the process whereby excess glucose 6-phosphate is converted into glycogen. The glycogen is stored in the liver and in muscle tissue (Section 24.5). Glycogenolysis. Glycogenolysis is the breakdown of glycogen into glucose 6-phosphate. This process occurs when muscles need energy and when the liver is restoring a low blood-sugar level to normal (Section 24.5).

Gluconeogenesis. Gluconeogenesis is the formation of glucose from pyruvate, lactate, and certain other substances. This process takes place in the liver when glycogen supplies are being depleted and when carbohydrate intake is low (Section 24.6). Cori cycle. The Cori cycle is the cyclic process involving the transport of lactate from muscle tissue to the liver, the resynthesis of glucose by gluconeogenesis, and the return of glucose to muscle tissue (Section 24.6). Pentose phosphate pathway. The pentose phosphate pathway metabolizes glucose to produce ribose (a pentose), NADPH, and other sugars needed for biosynthesis (Section 24.8). Carbohydrate metabolism and hormones. Insulin decreases blood-glucose levels by promoting the uptake of glucose by cells. Glucagon increases blood-glucose levels by promoting the conversion of glycogen to glucose. Epinephrine stimulates the release of glucose from glycogen in muscle cells (Section 24.9).

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Chapter 24 Carbohydrate Metabolism

EY R E A C T I O N S A N D E Q U AT I O N S

1. Glycolysis (Section 24.2)

5. Complete oxidation of glucose (Section 24.4) ⫹

Glucose ⫹ 2Pi ⫹ 2ADP ⫹ 2NAD 88n 2 pyruvate ⫹ 2ATP ⫹ 2NADH ⫹ 2H⫹ ⫹ 2H2O 2. Oxidation of pyruvate to acetyl CoA (Section 24.3) O B CH3O C O COO⫺ ⫹ CoAOSH ⫹ NAD⫹

Four steps

O B CH3 O C OSO CoA ⫹ NADH ⫹ CO2 3. Reduction of pyruvate to lactate (Section 24.3) O B CH3O C O COO⫺ ⫹ NADH ⫹ H⫹

OH A CH3 O CH OCOO⫺ ⫹ NAD⫹

Glucose ⫹ 6O2 ⫹ 30ADP ⫹ 30Pi ¡

6CO2 ⫹ 6H2O ⫹ 30ATP

6. Glycogenesis (Section 24.5) Glucose 6-phosphate Three 88 8n glycogen steps 7. Glycogenolysis (Section 24.5) Two Glycogen 88 8n glucose 6-phosphate steps

8. Gluconeogenesis (Section 24.6) Lactate, certain ⎫ amino acids, ⎪⎬ Eleven 8888n pyruvate 888 8n glucose steps citric acid cycle ⎪ intermediates ⎭

4. Reduction of pyruvate to ethanol (Section 24.3) O B CH3O C O COO⫺ ⫹ 2H⫹ ⫹ NADH

Two steps

CH3 O CH2 OOH ⫹ NAD⫹ ⫹ CO2

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Carbohydrate Digestion (Section 24.1) 24.1 Where does carbohydrate digestion begin in the body, and what

is the name of the enzyme involved in this initial digestive process? 24.2 Very little digestion of carbohydrates occurs in the stomach. Why? 24.3 What is the primary site for carbohydrate digestion, and what

organ produces the enzymes that are active at this location? 24.4 Where does the final step in carbohydrate digestion take place, and in what form are carbohydrates as they enter this final step? 24.5 Where does the digestion of sucrose begin, and what is the

reaction that occurs? 24.6 Where does the digestion of lactose begin, and what is the reaction that occurs? 24.7 Identify the three major monosaccharides produced by

digestion of carbohydrates. 24.8 The various stages of carbohydrate digestion all involve the same general type of reaction. What is this reaction type? Glycolysis (Section 24.2) 24.9 What is the starting material for glycolysis? 24.10 What is the end product from glycolysis? 24.11 What coenzyme functions as the oxidizing agent in glycolysis?

24.12 What is meant by the statement that glycolysis is an anaerobic

pathway?

24.13 What is the first step of glycolysis, and why is it important in

retaining glucose inside the cell?

24.14 Step 3 of glycolysis is the commitment step. Explain. 24.15 What two C3 fragments are formed by the splitting of a fructose

1,6-bisphosphate molecule? 24.16 In one step of the glycolysis pathway, a C6 chain is broken into two C3 fragments, only one of which can be further degraded. What happens to the other C3 fragment?

24.17 How many pyruvate molecules are produced per glucose mole-

cule during glycolysis?

24.18 How many molecules of ATP and NADH are produced per glu-

cose molecule during glycolysis?

24.19 How many steps in the glycolysis pathway produce ATP? 24.20 How many steps in the glycolysis pathway consume ATP? 24.21 Of the 10 steps of glycolysis, which ones involve phosphorylation? 24.22 Of the 10 steps of glycolysis, which ones involve oxidation? 24.23 Where in a cell does glycolysis occur? 24.24 Do the reactions of glycolysis and the citric acid cycle occur at

the same location in a cell? Explain.

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Exercises and Problems

24.25 Replace the question mark in each of the following word equa-

tions with the name of a substance. Hexokinase

Enolase

b. ? 78888n phosphoenolpyruvate  water ? c. 3-Phosphoglycerate 788n 2-phosphoglycerate Phosphoglycero8888888888n kinase

3-phosphoglycerate  ATP 24.26 Replace the question mark in each of the following word equa-

tions with the name of a substance. a. Glucose 6-phosphate

Phosphogluco7888888888n isomerase

?

Aldolase

b. ? 78888n dihydroxyacetone phosphate  glyceraldehyde 3-phosphate c. Phosphoenolpyruvate  ?

Fates of Pyruvate (Section 24.3) 24.35 What are the three common possible fates for pyruvate pro-

a. Glucose  ATP 7888888n ?  ADP

d. 1,3-Bisphosphoglycerate  ?

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Pyruvate 78888n kinase

pyruvate  ATP ? d. Dihydroxyacetone phosphate 88n glyceraldehyde 3-phosphate

24.27 In which step of glycolysis does each of the following occur?

a. Second substrate-level phosphorylation reaction b. First ATP-consuming reaction c. Third isomerization reaction d. Use of NAD as an oxidizing agent 24.28 In which step of glycolysis does each of the following occur? a. First energy-producing reaction b. First ATP-producing reaction c. A dehydration reaction d. First isomerization reaction 24.29 What is the net ATP production when each of the following

molecules is processed through the glycolysis pathway? a. One glucose molecule b. One sucrose molecule 24.30 What is the net ATP production when each of the following molecules is processed through the glycolysis pathway? a. One lactose molecule b. One maltose molecule 24.31 Draw structural formulas for each of the following pairs of

molecules. a. Pyruvic acid and pyruvate b. Dihydroxyacetone and dihydroxyacetone phosphate c. Fructose 6-phosphate and fructose 1,6-bisphosphate d. Glyceric acid and glyceraldehyde 24.32 Draw structural formulas for each of the following pairs of molecules. a. Glyceric acid and glycerate b. Glycerate and pyruvate c. Glucose 6-phosphate and fructose 6-phosphate d. Dihydroxyacetone and glyceric acid 24.33 Number the carbon atoms of fructose 1,6-bisphosphate 1 through

6, and show the location of each carbon in the two trioses produced during Step 4 of glycolysis. 24.34 Number the carbon atoms of glucose 1 through 6, and show the location of each carbon in the two molecules of pyruvate produced by glycolysis.

duced from glycolysis?

24.36 Compare the fates of pyruvate in the body under aerobic and

anaerobic conditions.

24.37 What is the overall reaction equation for the conversion of

pyruvate to acetyl CoA? 24.38 What is the overall reaction equation for the conversion of pyruvate to lactate? 24.39 Explain how lactate fermentation allows glycolysis to continue

under anaerobic conditions.

24.40 How is the ethanol fermentation in yeast similar to lactate

fermentation in skeletal muscle?

24.41 In ethanol fermentation, a C3 pyruvate molecule is changed to a C2

ethanol molecule. What is the fate of the third pyruvate carbon?

24.42 What are the structural differences between pyruvate and lactate

ions?

24.43 What is the net reaction for the conversion of one glucose mole-

cule to two lactate molecules?

24.44 What is the net reaction for the conversion of one glucose mole-

cule to two ethanol molecules?

Complete Oxidation of Glucose (Section 24.4) 24.45 How does the fact that cytosolic NADH/H cannot cross the mitochondrial membranes affect ATP production from cytosolic NADH/H? 24.46 What is the net reaction for the shuttle mechanism involving glycerol 3-phosphate by which NADH electrons are shuttled across the mitochondrial membrane? 24.47 Contrast, in terms of ATP production, the oxidation of

glucose to CO2 and H2O with the oxidation of glucose to pyruvate. 24.48 Contrast, in terms of ATP production, the oxidation of glucose to CO2 and H2O with the oxidation of glucose to ethanol. 24.49 How many of the 30 ATP molecules produced from the com-

plete oxidation of 1 glucose molecule are produced during glycolysis? 24.50 How many of the 30 ATP molecules produced from the complete oxidation of 1 glucose molecule are produced during the oxidation of pyruvate to acetyl CoA? Glycoge n Metabolism (Section 24.5) 24.51 Compare the meanings of the terms glycogenesis and glycogenolysis. 24.52 Where is most of the body’s glycogen stored? 24.53 Glucose 1-phosphate is the product of the first step of

glycogenesis. What is the reactant?

24.54 Glucose 1-phosphate is the product of the first step of

glycogenolysis. What are the reactants?

24.55 What is the source of the PPi produced during the second step

of glycogenesis?

24.56 What is the function of the PPi produced during the second step

of glycogenesis?

24.57 How is ATP involved in glycogenesis? 24.58 How many ATP molecules are needed to attach a single glucose

molecule to a growing glycogen chain?

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Chapter 24 Carbohydrate Metabolism

24.59 Which step of glycogenolysis is the reverse of Step 1 of

glycogenesis?

24.60 What reaction determines whether glucose 6-phosphate formed

by glycogenolysis can leave a cell?

24.61 What is the difference between the processing of glucose

6-phosphate in liver cells and that in muscle cells?

24.62 The liver, but not the brain or muscle cells, has the capacity to

supply free glucose to the blood. Explain.

24.63 In what form does glycogen enter the glycolysis pathway? 24.64 Explain why one more ATP is produced when glucose is ob-

tained from glycogen than when it is obtained directly from the blood.

Gluconeogenesis (Section 24.6) 24.65 What organ is primarily responsible for gluconeogenesis? 24.66 What is the physiological function of gluconeogenesis? 24.67 How does gluconeogenesis get around the three irreversible

steps of glycolysis?

24.68 Although gluconeogenesis and glycolysis are “reverse” proc-

esses, there are 11 steps in gluconeogenesis and only 10 steps in glycolysis. Explain.

24.69 What intermediate in gluconeogenesis is also an intermediate in

the citric acid cycle?

24.70 What are the sources of high-energy bonds in gluconeogenesis? 24.71 What is the fate of lactate formed by muscular activity? 24.72 What is the physiological function of the Cori cycle?

Terminology for Glucose Metabolic Pathways (Section 24.7) 24.73 Indicate in which of the four processes glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis each of the following compounds is encountered. There may be more than one correct answer for a given compound. a. Glucose 6-phosphate b. Dihydroxyacetone phosphate c. Oxaloacetate d. UDP-glucose 24.74 Indicate in which of the four processes glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis each of the following compounds is encountered. There may be more than one correct answer for a given compound. a. Glucose 1-phosphate b. Glycogen c. Pyruvate d. Fructose 6-phosphate 24.75 Indicate in which of the four processes glycolysis, glycogenesis,

glycogenolysis, and gluconeogenesis each of the following situations is encountered. There may be more than one correct answer for each. a. NAD is consumed. b. ATP is produced. c. UDP is involved. d. ADP is consumed. 24.76 Indicate in which of the four processes glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis each of the following

situations is encountered. There may be more than one correct answer for each. a. NADH is consumed. b. ATP is consumed. c. CO2 is involved. d. H2O is a product. 24.77 Indicate in which of the four processes glycolysis, glycogenesis,

glycogenolysis, and gluconeogenesis each of the following enzymes is needed. There may be more than one correct answer for each. a. Fructose 1,6-bisphosphatase. b. Pyruvate kinase. c. Glycogen synthase. d. Phosphoglucomutase. 24.78 Indicate in which of the four processes glycolysis, glycogenesis, glycogenolysis, and gluconeogenesis each of the following enzymes is needed. There may be more than one correct answer for each. a. Pyruvate carboxylase. b. Glycogen phosphorylase. c. Hexokinase. d. Glucose 6-phosphatase. The Pentose Phosphate Pathway (Section 24.8) 24.79 What is the starting material for the pentose phosphate

pathway?

24.80 What are two major functions of the pentose phosphate

pathway?

24.81 How do the biochemical functions of NADH and NADPH

differ?

24.82 How do the structures of NADH and NADPH differ? 24.83 Write a general equation for the oxidative stage of the pentose

phosphate pathway.

24.84 Write a general equation for the entire pentose phosphate

pathway.

24.85 What compound contains the carbon atom lost from glucose

(a hexose) in its conversion to ribose (a pentose)?

24.86 How many molecules of NADPH are produced per glucose

6-phosphate in the pentose phosphate pathway?

Control of Carbohydrate Metabolism (Section 24.9) 24.87 What effect does insulin have on glycogen metabolism? 24.88 What effect does insulin have on blood-glucose levels? 24.89 What effect does glucagon have on blood-glucose levels? 24.90 What effect does glucagon have on glycogen metabolism? 24.91 What organ is the source of insulin? 24.92 What organ is the source of glucagon? 24.93 The hormone epinephrine generates a “second messenger.”

Explain. 24.94 What is the relationship between cAMP and the hormone epinephrine? 24.95 Compare the target tissues for glucagon and epinephrine.

24.96 Compare the biological functions of glucagon and epinephrine.

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Multiple-Choice Practice Test

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A DD D ITIONAL P R O BL L EMS 24.97 What is the ATP yield per glucose molecule in each of the

following processes? a. Glycolysis b. Glycolysis, acetyl CoA formation, and the common metabolic pathway c. Glycolysis plus oxidation of pyruvate to acetyl CoA d. Glycolysis plus reduction of pyruvate to lactate 24.98 Which one of these characterizations, (1) Cori cycle, (2) an anaerobic process, (3) oxidative stage of pentose phosphate pathway, or (4) nonoxidative stage of pentose phosphate pathway, applies to each of the following chemical changes? a. Pyruvate to lactate b. Pyruvate to ethanol c. Glucose 6-phosphate to ribulose 5-phosphate d. Ribulose 5-phosphate to ribose 5-phosphate 24.99 What condition or conditions determine that pyruvate is involved in each of the following? a. Gluconeogenesis b. Converted to lactate

c. Citric acid cycle d. Converted to ethanol 24.100 In the complete metabolism of 1 mole of sucrose, how many moles of each of the following are produced? a. CO2 b. Pyruvate c. Acetyl CoA d. ATP 24.101 Under what conditions does glucose 6-phosphate enter each of the following processes. a. Glycogenesis b. Glycolysis c. Pentose phosphate pathway d. Hydrolysis to free glucose

multiple-Choice Practice Test 24.102 Which of the following statements concerning glycolysis is

24.103

24.104

24.105

24.106

correct? a. It is an oxidation process in which molecular oxygen is used. b. All reactions take place in the cytosol of a cell. c. There are two stages, each of which involves a series of five reactions. d. The overall process converts a C6 molecule into three C2 molecules. What are the two steps in glycolysis in which ATP is converted to ADP? a. 1 and 2 b. 1 and 3 c. 2 and 3 d. 7 and 10 Intermediates in the glycolysis pathway include two derivatives of which of the following? a. Glucose b. Fructose c. Pyruvate d. Glyceraldehyde What are the total number of steps in the C6 stage and C3 stage of glycolysis, respectively? a. 10 and 10 b. 5 and 5 c. 4 and 6 d. 3 and 7 During the overall process of glycolysis, which of the following occurs for each glucose molecule processed? a. Net loss of two ATP molecules b. Net loss of four ATP molecules

24.107

24.108

24.109

24.110

24.111

c. Net gain of two ATP molecules d. Net gain of four ATP molecules Lactate fermentation can occur in which of the following? a. Humans, animals, and microorganisms b. Humans and animals but not in microorganisms c. Microorganisms but not in humans and animals d. Microorganisms and animals but not in humans What is the name of the process in which glycogen is converted to glucose 6-phosphate? a. Glycolysis b. Glycogenolysis c. Glycogenesis d. Glyconeogenesis The compound oxaloacetate is an intermediate in which of the following conversions? a. Glycogen to glucose b. Glucose to glycogen c. Pyruvate to glucose d. Pyruvate to acetyl CoA As part of the Cori cycle, which of the following occurs in liver cells? a. Glucose is converted to pyruvate. b. Glucose is converted to lactate. c. Pyruvate is converted to lactate. d. Lactate is converted to pyruvate. Which of the following are products of the first stage of the pentose phosphate pathway? a. Ribose 5-phosphate and ribulose 5-phosphate b. Ribose 5-phosphate and carbon dioxide c. Ribulose 5-phosphate and carbon dioxide d. Ribose and carbon dioxide

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Lipid Metabolism Chapter Outline 25.1 Digestion and Absorption of Lipids 842 25.2 Triacylglycerol Storage and Mobilization 845

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25

25.3 Glycerol Metabolism 846 25.4 Oxidation of Fatty Acids

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25.5 ATP Production from Fatty Acid Oxidation 851 25.6 Ketone Bodies 854 25.7 Biosynthesis of Fatty Acids: Lipogenesis 858 25.8 Relationship Between Lipogenesis and Citric Acid Cycle Intermediates 864 25.9 Biosynthesis of Cholesterol 864

CHEMISTRY AT A GLANCE: Interrelationships Between Carbohydrate and Lipid Metabolism 868 25.10 Relationships Between Lipid and Carbohydrate Metabolism 869

CHEMICAL CONNECTIONS High-Intensity Versus Low-Intensity Workouts 853 Statins: Drugs That Lower Plasma Levels of Cholesterol 867

The fat stored in a camel's hump serves not only as a source of energy but also as a source of water. Water is one of the products of fat (triacylglycerol) metabolism.

C

ertain classes of lipids play an extremely important role in cellular metabolism, because they represent an energy-rich “fuel” that can be stored in large amounts in adipose (fat) tissue. Between one-third and one-half of the calories present in the diet of the average U.S. resident are supplied by lipids. Furthermore, excess energy derived from carbohydrates and proteins beyond normal daily needs is stored in lipid molecules (in adipose tissue), later to be mobilized and used when needed.

25.1 DIGESTION AND ABSORPTION OF LIPIDS The saliva of infants contains a lipase that can hydrolyze TAGs, so digestion begins in the mouth for nursing infants. Because mother’s milk is already a lipid-in-water emulsion, emulsification by stomach churning is a much less important factor in an infant’s processing of fat. Mother’s milk also contains a lipase that supplements the action of the salivary lipases the infant itself produces. After weaning, infants cease to produce salivary lipases.

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Because 98% of total dietary lipids are triacylglycerols (fats and oils; Section 19.4), this chapter focuses on triacylglycerol metabolism. Like all lipids, triacylglycerols (TAGs) are insoluble in water. Hence, water-based salivary enzymes in the mouth have little effect on them. The major change that TAGs undergo in the stomach is physical rather than chemical. The churning action of the stomach breaks up triacylglycerol materials into small globules, or droplets, which float as a layer above the other components of swallowed food. The resulting material is called chyme. High-fat foods remain in the stomach longer than low-fat foods. The conversion of high-fat materials into chyme takes longer than the breakup of low-fat materials. This is why a high-fat meal causes a person to feel “full” for a longer period of time. Lipid digestion also begins in the stomach. Under the action of gastric lipase enzymes, hydrolysis of TAGs occurs. Normally, about 10% of TAGs undergo hydrolysis in the

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25.1 Digestion and Absorption of Lipids

Figure 25.1 In a fatty acid micelle, the hydrophobic chains of the fatty acids and monoacylglycerols are in the interior of the micelle.

stomach, but regular consumption of a high-fat diet can induce the production of higher levels of gastric lipases. The arrival of chyme from the stomach triggers in the small intestine, through the action of the hormone cholecystokinin, the release of bile stored in the gallbladder. The bile (Section 19.11), which contains no enzymes, acts as an emulsifier (Section 19.11). Colloid particle formation (Section 8.7) through bile emulsification “solubilizes” the triacylglycerol globules, and digestion of the TAGs resumes. The major enzymes involved at this point are the pancreatic lipases, which hydrolyze ester linkages between the glycerol and fatty acid units of the TAGs. Complete hydrolysis does not usually occur; only two of the three fatty acid units are liberated, producing a monoacylglycerol and two free fatty acids. Occasionally, enzymes remove all three fatty acid units, leaving a free glycerol molecule. G l y c e r o l

Fatty acid Lipases Fatty acid

Fatty acid Triacylglycerol

When freed of the triacylglycerol molecules they “transport” during digestion, bile acids are mostly recycled. Small amounts are excreted.

Chylomicron is pronounced “kye-lo-MY-cron.”

Triacylglycerols (TAGs) Protein Membrane lipids

Figure 25.2 A three-dimensional model of a chylomicron, a type of lipoprotein. Chylomicrons are the form in which TAGs are delivered to the bloodstream via the lymphatic system.

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+ 2H2O

G l y c e r o l

OH

Fatty acid

+ 2 Fatty acid

OH

Monoacylglycerol

Free fatty acids

With the help of bile, the free fatty acids and monoacylglycerols produced from hydrolysis are combined into tiny spherical droplets called micelles (Section 19.6). A fatty acid micelle is a micelle in which fatty acids and/or monoacylglycerols and some bile are present. Fatty acid micelles are very small compared to the original triacylglycerol globules, which contain thousands of triacylglycerol molecules. Figure 25.1 shows a cross section of the three-dimensional structure of a fatty acid micelle. Micelles, containing free fatty acid and monoacylglycerol components, are small enough to be readily absorbed through the membranes of intestinal cells. Within the intestinal cells, a “repackaging” occurs in which the free fatty acids and monoacylglycerols are reassembled into triacylglycerols. The newly formed triacylglycerols are then combined with membrane lipids (phospholipids and cholesterol) and water-soluble proteins to produce a type of lipoprotein (Section 20.18) called a chylomicron (see Figure 25.2). A chylomicron is a lipoprotein that transports triacylglycerols from intestinal cells, via the lymphatic system, to the bloodstream. Triacylglycerols constitute 95% of the core lipids present in a chylomicron. Chylomicrons are too large to pass through capillary walls directly into the bloodstream. Consequently, delivery of the chylomicrons to the bloodstream is accomplished through the body’s lymphatic system. Chylomicrons enter the lymphatic system through tiny lymphatic vessels in the intestinal lining. They enter the bloodstream through the thoracic duct (a large lymphatic vessel just below the collarbone), where the fluid of the lymphatic system flows into a vein, joining the bloodstream. Once the chylomicrons reach the bloodstream, the TAGs they carry are again hydrolyzed to produce glycerol and free fatty acids. TAG release from chylomicrons and their ensuing hydrolysis is mediated by lipoprotein lipases. These enzymes are located on the lining of blood vessels in muscle and other tissues that use fatty acids for fuel and in fat synthesis. The fatty acid and glycerol hydrolysis products from TAG hydrolysis are absorbed by the cells of the body and are either broken down to acetyl CoA for energy or stored as lipids (they are again repackaged as TAGs). Figure 25.3 summarizes the events that must occur before triacylglycerols can reach the bloodstream through the digestive process. Soon after a meal heavily laden with TAGs is ingested, the chylomicron content of both blood and lymph increases dramatically. Chylomicron concentrations usually begin to rise within 2 hours after a meal, reach a peak in 4–6 hours, and then drop

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Chapter 25 Lipid Metabolism

Dietary triacylglycerols (TAGs)

1. Mouth

Fat droplets in chyme Some monoacylglycerols

Saliva—no effect on digestion

Free fatty acids in bloodstream

6. Bloodstream

2. Stomach

TAGs in bloodstream

5. Lymphatic System

TAGs are hydrolyzed to free fatty acids

3. Small Intestine

Churning action—produces small fat droplets (chyme) Gastric lipases—hydrolyze some (10%) TAGs

Bile—solubilizes “droplets” Pancreatic lipases—produce monoacylglycerols, which form fatty acid micelles

TAGs in chylomicrons

Transport to bloodstream

4. Intestinal Cells

Monoacylglycerols in micelles

Micelles “repackaged” into TAGs, which form chylomicrons

Figure 25.3 A summary of the events that must occur before triacylglycerols (TAGs) can reach the bloodstream through the digestive process.

rather rapidly to a normal level as they move into adipose cells (Section 25.2) or into the liver.

Based on the information in Figure 25.3, determine the location within the human body where each of the following aspects of lipid digestion occurs. a. b. c. d.

Interaction with bile occurs. Monoacylglycerols are produced. Chyme is produced. Gastric lipases are active.

Solution

a. The small intestine is the location where bile released from the gallbladder interacts with the fat droplets present in chyme. The bile functions as an emulsifying agent. b. Pancreatic lipases present in the small intestine convert triacylglycerols to monoacylglycerols. c. The churning action of the stomach breaks triacylglycerol materials into small droplets that float on top of other ingested food materials; the resulting mixture is called chyme. d. Gastric lipases present in the stomach begin the triacylglycerol hydrolysis process; about 10% of triacylglycerols undergo hydrolysis in the stomach.

Practice Exercise 25.1 Based on the information in Figure 25.3, determine the location within the human body where each of the following aspects of lipid digestion occurs. a. b. c. d.

Pancreatic lipases are active. Fatty acid micelles are produced. Chylomicrons are produced. Monoacylglycerols are converted back to triacylglycerols.

Answers: a. Small intestine; b. Small intestine; c. Intestinal cells; d. Intestinal cells

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25.2 Triacylglycerol Storage and Mobilization

Dietary TAGs deposited in adipose tissue have undergone hydrolysis two times (to form free fatty acids and/or monoacylglycerols) and are repackaged twice (to re-form TAGs) in reaching that state. They undergo hydrolysis for a third time when triacylglycerol mobilization occurs.

Adipose tissue is the only tissue in which free TAGs occur in appreciable amounts. In other types of cells and in the bloodstream, TAGs are part of lipoprotein particles.

Cytosol

Large central globule of triacylglycerol

Cell nucleus

Figure 25.4 Structural characteristics of an adipose cell.

B

F

The use of cAMP in the activation of hormone-sensitive lipase in adipose cells is similar to cAMP’s role in the activation of the glycogenolysis process (Section 24.9).

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25.2 TRIACYLGLYCEROL STORAGE AND MOBILIZATION Most cells in the body have limited capability for storage of TAGs. However, this activity is the major function of specialized cells called adipocytes, found in adipose tissue. An adipocyte is a triacylglycerol-storing cell. Adipose tissue is tissue that contains large numbers of adipocyte cells. Adipose tissue is located primarily directly beneath the skin (subcutaneous), particularly in the abdominal region, and in areas around vital organs. Besides its function as a storage location for the chemical energy inherent in TAGs, subcutaneous adipose tissue also serves as an insulator against excessive heat loss to the environment and provides organs with protection against physical shock. Adipose cells are among the largest cells in the body. They differ from other cells in that most of the cytoplasm has been replaced with a large triacylglycerol droplet (Figure 25.4). This droplet accounts for nearly the entire volume of the cell. As newly formed TAGs are imported into an adipose cell, they form small droplets at the periphery of the cell that later merge with the large central droplet. Use of the TAGs stored in adipose tissue for energy production is triggered by several hormones, including epinephrine and glucagon. Hormonal interaction with adipose cell membrane receptors stimulates production of cAMP from ATP inside the adipose cell. In a series of enzymatic reactions, the cAMP activates hormone-sensitive lipase (HSL) through phosphorylation. HSL is the lipase needed for triacylglycerol hydrolysis, a prerequisite for fatty acids to enter the bloodstream from an adipose cell. This cAMP activation process is illustrated in Figure 25.5. The overall process of tapping the body’s triacylglycerol energy reserves (adipose tissue) for energy is called triacylglycerol mobilization. Triacylglycerol mobilization is the hydrolysis of triacylglycerols stored in adipose tissue, followed by release into the bloodstream of the fatty acids and glycerol so produced. Triacylglycerol mobilization is an ongoing process. On the average, about 10% of the TAGs in adipose tissue are replaced daily by new triacylglycerol molecules. Triacylglycerol energy reserves (fat reserves) are the human body’s major source of stored energy. Energy reserves associated with protein, glycogen, and glucose are small to very small when compared to fat reserves. Table 25.1 shows relative amounts of stored energy associated with the various types of energy reserves present in the human body.

Epinephrine cAMP Receptor site

ATP

HSL (inactive)

Adenyl cyclase Cell membrane

Fatty acids + glycerol

Phosphorylation

HSL– P (active)

Triacylglycerols

Interior of adipose cell

Fatty acids + glycerol

Figure 25.5 Hydrolysis of stored triacylglycerols in adipose tissue is triggered by hormones that stimulate cAMP production within adipose cells.

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Chapter 25 Lipid Metabolism

TABLE 25.1 Stored Energy Reserves of Various Types for a 150-lb (70-kg) Person

Triacylglycerol reserves would enable the average person to survive starvation for about 30 days, given sufficient water. Glycogen reserves (stored glucose) would be depleted within 1 day.

Type of Energy Reserve

Amount of Stored Energy

triacylglycerol protein glycogen blood glucose

Percent of Total Stored Energy

135,000 kcal 24,000 kcal 720 kcal 80 kcal

84.3% 15% 0.45% 0.05%

25.3 GLYCEROL METABOLISM During triacylglycerol mobilization, one molecule of glycerol is produced for each triacylglycerol completely hydrolyzed. Glycerol metabolism primarily involves processes considered in the previous chapter. After entering the bloodstream, glycerol travels to the liver or kidneys, where it is converted, in a two-step process, to dihydroxyacetone phosphate. H2CO OH A HCO OH A H2CO OH

Glycerol kinase ATP

Glycerol

ADP

H2CO OH A HCO OH A H2CO OO P

Glycerol 3-phosphate dehydrogenase NAD

NADH/H

H2CO OH A CP O A H2COOO P Dihydroxyacetone phosphate

Glycerol 3-phosphate

The first step involves phosphorylation of a primary hydroxyl group of the glycerol. In the second step, glycerol’s secondary alcohol group (C-2) is oxidized to a ketone. The following equation represents the overall reaction for the metabolism of glycerol. Glycerol  ATP  NAD ¡ Dihydroxyacetone phosphate  ADP  NADH  H Dihydroxyacetone phosphate is an intermediate in both glycolysis (Section 24.2) and gluconeogenesis (Section 24.6). It can be converted to pyruvate, then acetyl CoA, and finally carbon dioxide, or it can be used to form glucose. Dihydroxyacetone phosphate formation from glycerol represents the first of several situations we will consider wherein carbohydrate and lipid metabolism are connected.

25.4 OXIDATION OF FATTY ACIDS The stored TAGs in adipose tissue supply approximately 60% of the body’s energy needs when the body is in a resting state.

There are three parts to the process by which fatty acids are broken down to obtain energy. 1. The fatty acid must be activated by bonding to coenzyme A. 2. The fatty acid must be transported into the mitochondrial matrix by a shuttle mechanism. 3. The fatty acid must be repeatedly oxidized, cycling through a series of four reactions, to produce acetyl CoA, FADH2, and NADH.

Fatty Acid Activation The outer mitochondrial membrane is the site of fatty acid activation, the first stage of fatty acid oxidation. Here the fatty acid is converted to a high-energy derivative of coenzyme A. Reactants are the fatty acid, coenzyme A, and a molecule of ATP. O B RO COO  HS O CoA

Acyl CoA synthetase

Free fatty acid ATP

AMP  2Pi

O B ROCO S O CoA Acyl CoA

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25.4 Oxidation of Fatty Acids

B

F

Recall, from Section 16.19, that acyl is a generic term for O B R OC O which is the species formed when the carboxyl —OH is removed from a carboxylic acid. The R group can involve a carbon chain of any length.

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This reaction requires the expenditure of two high-energy phosphate bonds from a single ATP molecule; the ATP is converted to AMP rather than ADP, and the resulting pyrophosphate (PPi) is hydrolyzed to 2Pi. The activated fatty acid–CoA molecule is called acyl CoA. The difference between the designations acyl CoA and acetyl CoA is that acyl refers to a random-length fatty acid carbon chain that is covalently bonded to coenzyme A, whereas acetyl refers to a two-carbon chain covalently bonded to coenzyme A. O B RO CO S O CoA

O B CH3 O CO S OCoA

Acyl CoA R ⫽ carbon chain of any length

Acetyl CoA R ⫽ CH3 group

Fatty Acid Transport Acyl CoA is too large to pass through the inner mitochondrial membrane to the mitochondrial matrix, where the enzymes needed for fatty acid oxidation are located. A shuttle mechanism involving the molecule carnitine effects the entry of acyl CoA into the matrix (see Figure 25.6). The acyl group is transferred to a carnitine molecule, which carries it through the membrane. The acyl group is then transferred from the carnitine back to a CoA molecule.

Reactions of the ␤-Oxidation Pathway

B

F

We have encountered an identical set of functional group changes before, in the back side of the citric acid cycle (Section 23.6), Steps 6–8 of this cycle.

In the mitochondrial matrix, a sequence of four reactions repeatedly cleaves two-carbon units from the carboxyl end of the acyl CoA molecule. This repetitive four-reaction sequence is called the b-oxidation pathway because the second carbon from the carboxyl end of the chain, the beta carbon, is the carbon atom that is oxidized. The ␤-oxidation pathway is a repetitive series of four biochemical reactions that degrades acyl CoA to acetyl CoA by removing two carbon atoms at a time, with FADH2 and NADH also being produced. Each repetition of the four-reaction sequence generates an acetyl CoA molecule and an acyl CoA molecule that has two fewer carbon atoms. For a saturated fatty acid, the b-oxidation pathway involves the following functional group changes at the b carbon and the following reaction types. Alkane

1

2

Oxidation

Hydration

(dehydrogenation)

Figure 25.6 Fatty acids are transported across the inner mitochondrial membrane in the form of acyl carnitine.

alkene

Carnitine + N(CH3)3

3 Oxidation

secondary alcohol

(dehydrogenation)

Acyl Carnitine Acyl CoA

+ N(CH3)3

CoA

Mitochondrial CH2 intermembrane space HO CH

CH2

O R

CH2

C

O

Acyl group

CH CH2 COO–

–

COO

Inner mitochondrial membrane + N(CH3)3

Mitochondrial matrix

+ N(CH3)3

CH2 HO

CH2

O

CH

R

CH2

Acyl CoA –

COO

CoA

C

O

Acyl group

CH CH2 COO–

4

ketone

Chain cleavage

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Details about Steps 1–4 of the b-oxidation pathway follow. Step 1:

Oxidation (dehydrogenation). Hydrogen atoms are removed from the a and b carbons, creating a double bond between these two carbon atoms. FAD is the oxidizing agent, and a FADH2 molecule is a product. H H O A A B RO CO COCO S O CoA A A H H

Acyl CoA dehydrogenase FAD

H O A B RO CP CO CO S O CoA A H 

FADH2

trans-Enoyl CoA

Acyl CoA

The enzyme involved is stereospecific in that only trans double bonds are produced. Step 2: Hydration. A molecule of water is added across the trans double bond, producing a secondary alcohol at the b-carbon position. Again, the enzyme involved is stereospecific in that only the L-hydroxy isomer is produced from the trans double bond. H O A B RO CP COCO S O CoA A H

Enoyl CoA hydratase H2O

OH H O A A B RO CO CO CO S O CoA A A H H L - -Hydroxyacyl

trans-Enoyl CoA

B

F

The reaction sequence dehydrogenation–hydration– dehydrogenation in the fatty acid spiral has a parallel in Steps 6–8 of the citric acid cycle (Section 23.6), where succinate is dehydrogenated to fumarate, which is hydrated to malate, which is dehydrogenated to oxaloacetate.

CoA

The enzyme involved in this hydration will also hydrate a cis double bond, but the product then is the D isomer. We shall return to this point later in considering how unsaturated fatty acids are oxidized. Step 3: Oxidation (dehydrogenation). The b-hydroxy group is oxidized to a ketone functional group with NAD serving as the oxidizing agent. The required enzyme exhibits absolute stereospecificity for the L isomer. OH H O A A B RO CO COCO S O CoA A A H H L- -Hydroxyacyl

 -Hydroxyacyl CoA dehydrogenase NAD

O O B B RO COCH2 OCO S O CoA

NADH  H

 -Ketoacyl CoA

CoA

It is now apparent why the name for this series of reactions is b-oxidation pathway. The b-carbon atom has been oxidized from a 9CH29 group to a ketone group. Step 4:

Chain Cleavage. The fatty acid chain is broken between the a and b carbons by reaction with a coenzyme A molecule. The result is an acetyl CoA molecule and a new acyl CoA molecule that is shorter by two carbon atoms than its predecessor. O O B B ROCO CH2 OC O S O CoA

Thiolase

 -Ketoacyl CoA

CoAO SH

O O B B ROC O S OCoA  CH3 OC O S O CoA Acyl CoA with two fewer carbon atoms

Acetyl CoA

The new acyl CoA molecule (now shorter by two carbons) is recycled through the same set of four reactions again. This yields another acetyl CoA, a two-carbon-shorter new acyl CoA, FADH2, and NADH. Recycling occurs again and again, until the entire fatty acid is converted to acetyl CoA. Thus the fatty acid carbon chain is sequentially degraded, two carbons at a time. Figure 25.7 summarizes the reactions of the b-oxidation pathway for stearic acid (18:0) as the starting fatty acid.

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25.4 Oxidation of Fatty Acids

Figure 25.7 Reactions of the

849

O

b-oxidation pathway for an 18:0 fatty acid (stearic acid).

C18

(CH2)14

CH3

CH2

CH2

C

S

CoA

FAD 1

Dehydrogenation

FADH2 O CH3

(CH2)14

CH

CH

C

S

CoA

S

CoA

H2O 2

Hydration

CH3

(CH2)14

OH

O

CH

CH2 C

NAD+ 3

Dehydrogenation

NADH + H+ O CH3

(CH2)14

C

O CH2

C CoA

4

S

CoA SH

Chain cleavage

O C16

CH3

(CH2)14

C

O S

CoA + CH3

C

S

CoA

C14 + Acetyl CoA C12 + Acetyl CoA Each loop of the pathway represents a repetition of Steps 1–4.

C10 + Acetyl CoA C8

+ Acetyl CoA

C6

+ Acetyl CoA

C4

+ Acetyl CoA 2 Acetyl CoA

This sequence of reactions is called the b-oxidation pathway rather than the b-oxidation cycle because a different product results from each repetition.

The fatty acids normally found in dietary triacylglycerols contain an even number of carbon atoms. Thus the number of acetyl CoA molecules produced in the b-oxidation pathway is equal to half the number of carbon atoms in the fatty acid. The number of repetitions of the b-oxidation pathway that are needed to produce the acetyl CoA is always one less than the number of acetyl CoA molecules produced because the last repetition produces two acetyl CoA molecules as a C4 unit splits into two C2 units. C18 fatty acid ¡ 9 acety1 CoA (8 repetitive sequences) C14 fatty acid ¡ 7 acety1 CoA (6 repetitive sequences)

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Chapter 25 Lipid Metabolism

Indicate at what step in the b-oxidation pathway each of the following events occurs. a. b. c. d.

A carbon–carbon single bond is converted to a carbon–carbon double bond. NAD is reduced to NADH. A hydration reaction occurs. An acetyl CoA molecule is produced.

Solution

a. Step 1. An oxidation reaction involving removal of two hydrogen atoms changes the carbon–carbon single bond to a carbon–carbon double bond. b. Step 3. This step is the second of two oxidation reactions that occur. The oxidizing agent for this oxidation is NAD, which is converted to NADH. Note that the oxidizing agent for the first oxidation reaction (step 1) is not NAD but rather FAD. c. Step 2. A molecule of water is added to the carbon–carbon double bond producing a secondary alcohol at the b-carbon position. d. Step 4. Breakage of the bond between the a- and b-carbon atoms produces an acetyl CoA molecule and an acyl CoA molecule whose carbon chain is two atoms shorter than at the start of the pathway.

Practice Exercise 25.2 Indicate at what step in the b-oxidation pathway each of the following events occurs. a. b. c. d.

A carbon–carbon double bond is converted to a carbon–carbon single bond. FAD is reduced to FADH2. A secondary alcohol group is oxidized to a ketone group. A coenzyme A molecule is needed as a reactant.

Answers: a. Step 2; b. Step 1; c. Step 3; d. Step 4

Match each of the following characteristics of the b-oxidation pathway to the terms (1) first oxidation, (2) hydration, (3) second oxidation, and (4) chain cleavage. a. b. c. d.

The enzyme needed is thiolase. The enzyme needed is acyl CoA dehydrogenase. The substance trans-enoyl CoA is a product. The substance b-ketoacyl CoA is a reactant.

Solution

a. Chain cleavage (Step 4). The prefix thio in the enzyme name thiolase indicates a reaction that involves an S bond. When coenzyme A reacts with the acyl group produced by chain cleavage to form acyl CoA a new C9S bond is formed. b. First oxidation (Step 1). This oxidation step, as well as the second one, involves the removal of two hydrogen atoms with the resulting creation of a double bond. A dehydrogenase enzyme effects such a change. c. First oxidation (Step 1). Trans-enoyl CoA is produced in Step 1 and becomes the reactant for Step 2. d. Chain cleavage (Step 4). b-ketoacyl CoA is produced in Step 3 and becomes the reactant for Step 4.

Practice Exercise 25.3 Match each of the following characteristics of the b-oxidation pathway to the terms (1) first oxidation, (2) hydration, (3) second oxidation, and (4) chain cleavage. a. The enzyme enoyl CoA hydratase is needed.

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b. A stereospecific enzyme that produces trans-carbon–carbon double bonds is needed. c. The substance acyl CoA is a reactant. d. The substance acyl CoA is a product. Answers: a. Hydration; b. First oxidation; c. First oxidation; d. Chain cleavage

Unsaturated Fatty Acids Unsaturated fatty acids are common components of dietary triacylglycerols. Their oxidation through the b-oxidation pathway requires two additional enzymes besides those needed for oxidation of saturated fatty acids. These two—an epimerase that can change a D configuration to an L configuration and a cis–trans isomerase—are needed for two reasons. First, the double bonds in naturally occurring unsaturated fatty acids are nearly always cis double bonds, which yield on hydration a D-hydroxy product rather than the L-hydroxy product needed for Step 3 of the pathway. The epimerase enzyme effects a configuration change from the D form to the L form. H H O A A B ROCO CO COSO CoA A A OH H D- -Hydroxyacyl

Epimerase

OH H O A A B ROCO CO COSO CoA A A H H L- -Hydroxyacyl

CoA

CoA

Second, the double bonds in naturally occurring unsaturated fatty acids often occupy odd-numbered positions (Section 19.2). The hydratase in Step 2 of the pathway can effect hydration of only an even-numbered double bond. The cis–trans isomerase produces a trans-(2,3) double bond from a cis-(3,4) double bond. O H H A A B Z O CPCO CH2O COSO CoA 4

3

2

cis-(3,4)

1

cistrans Isomerase

H O A B Z OCH2 OC PCO COSO CoA 3 A 2 4 1 H trans-(2,3)

The Step 2 hydratase can then work on the trans-(2,3) double bond in the normal fashion.

25.5 ATP PRODUCTION FROM FATTY ACID OXIDATION How does the total energy output from fatty acid oxidation compare to that of glucose oxidation? Let us calculate ATP production for the oxidation of a specific fatty acid molecule, stearic acid (18:0), and compare it with that from glucose. Figure 25.7 shows that for each four-reaction sequence except the last one, one FADH2 molecule, one NADH molecule, and one acetyl CoA molecule are produced. In the final four-reaction sequence, two acetyl CoA molecules are produced in addition to the FADH2 and NADH molecules. Eight repetitions of the b-oxidation pathway are required for the oxidation of stearic acid, an 18-carbon acid. These eight repetitions of the pathway produce 9 acetyl CoA molecules, 8 FADH2 molecules, and 8 NADH molecules. Further processing of these products through the common metabolic pathway (citric acid cycle,

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electron transport chain, and oxidative phosphorylation) leads to ATP production as follows: 10 ATP 9 acetyl CoA   90 ATP 1 acetyl CoA 1.5 ATP  12 ATP 8 FADH 2  1 FADH 2 2.5 ATP 8 NADH   20 ATP 1 NADH 122 ATP The conversion factors used in this calculation were first presented in Section 23.9. This gross production of 122 ATP must be decreased by the ATP needed to activate the fatty acid before it enters the b-oxidation pathway. The activation consumes two high-energy phosphate bonds of an ATP molecule. For accounting purposes, this is equivalent to hydrolyzing 2 ATP molecules to ADP. Thus the net ATP production from oxidation of stearic acid is 120 ATP (122 minus 2). What is the net ATP production for the complete oxidation of lauric acid, the C12 saturated fatty acid, to CO2 and H2O? Solution

The total ATP production for oxidation of a fatty acid is the sum of the ATP produced from the metabolic products FADH2, NADH, and acetyl CoA. In obtaining the net ATP production, it must be remembered that the activation of a fatty acid molecule prior to its oxidation requires ATP consumption equivalent to two ATP molecules (Section 25.4). Oxidation of a C12 fatty acid requires five passages through the four-reaction sequence of the b-oxidation pathway. These five repetitions produce a total of 6 acetyl CoA, 5 FADH2, and 5 NADH. The number of acetyl CoA produced is always equal to the number of carbon atoms present in the fatty acid divided by 2, which is 12/2  6 in this case. The number of FADH2 and NADH produced will always be one less than the number of acetyl CoA produced. Further processing of these metabolic products through the citric acid cycle, electron transport chain, and oxidative phosphorylation leads to ATP production as follows: Fatty Acid Activation:

2 ATP

Acetyl CoA Production: 6 acetyl CoA 3

10 ATP 1 acetyl CoA

60 ATP

FADH2 Production: 5 FADH 2 3

1.5 ATP 1 FADH 2

7.5 ATP

NADH Production: 5 NADH 3

2.5 ATP 1 NADH

Net ATP Production:

12.5 ATP 78 ATP

The ATP equivalents for acetyl CoA, FADH2, and NADH used in this calculation were first presented in Section 23.9.

Practice Exercise 25.4 What is the net ATP production for the complete oxidation of palmitic acid, the C16 saturated fatty acid, to CO2 and H2O? Answer: 106 ATP

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25.5 ATP Production from Fatty Acid Oxidation

853

The comparison between complete fatty acid oxidation and complete glucose oxidation (Section 24.4) shows that a stearic acid molecule produces four times as much ATP as a glucose molecule. 1 glucose 88n 30 ATP 1 stearic acid 88n 120 ATP Taking into account the fact that glucose has only 6 carbon atoms and stearic acid has 18 carbon atoms still shows more ATP production from the fatty acid. 3 glucose (18 C) 88n 90 ATP 1 stearic acid (18 C) 88n 120 ATP Thus, on the basis of equal numbers of carbon atoms, lipids are 33% more efficient than carbohydrates as energy-storage systems.

c

HEMICAL

onnections

High-Intensity Versus Low-Intensity Workouts

In a resting state, the human body burns more fat than carbohydrate. The fuel consumed is about one-third carbohydrate and two-thirds fat. Information about fuel consumption ratios is obtainable from respiratory gas measurements, specifically from the respiratory exchange ratio (RER). The RER is the ratio of carbon dioxide to oxygen inhaled divided by the ratio of carbon dioxide to oxygen exhaled. For 100% fat burning, the RER would be 0.7; for 100% carbohydrate burning, the RER would be 1.0. When a person at rest begins exercising, his or her body suddenly needs energy at a greater rate—more fuel and more oxygen are needed. It takes 0.7 L of oxygen to burn 1 gram of carbohydrate and 1.0 L of oxygen to burn 1 gram of fat. At the onset of exercise, the body is immediately short of oxygen. Also, there is a time delay in triacylglycerol mobilization. Triacylglycerols have to be broken down to fatty acids, which have to be

The initial stages of exercise are fueled primarily by glucose; in later stages, triacylglycerols become the primary fuel.

attached to protein carriers before they can be carried in the bloodstream to working muscles. At their destination, they must be released from the carriers and then undergo energyproducing reactions. By contrast, glycogen is already present in muscle cells, and it can release glucose 6-phosphate as an instant fuel. Consequently, the initial stages of exercise are fueled primarily by glucose—it requires less oxygen and can even be burned anaerobically (to lactate). During the first few minutes of exercise, up to 80% of the fuel used comes from glycogen. With time, increased breathing rates increase oxygen supplies to muscles, and triacylglycerol use increases. Continued activity for three-quarters of an hour achieves a 50–50 balance of triacylglycerol and glucose use. Beyond an hour, triacylglycerol use may be as high as 80%. Suppose a person is exercising at a moderate rate and decides to speed up. Immediately, body fuel and oxygen needs are increased. The response is increased use of glycogen supplies. The accompanying table compares exercise on a stationary cycle at 45% and 70% of maximum oxygen uptake sufficient to burn 300 calories.

percent of maximum oxygen uptake time required to burn 300 calories calories obtained from fat percent of calories from fat rate of fat burning per minute

Low-Intensity Exercise

High-Intensity Exercise

45%

70%

48 min

30 min

133 cal

65 cal

44%

22%

2.8 cal/min

2.1 cal/min

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On an equal-mass basis, fatty acids produce 2.5 times as much energy per gram as carbohydrates (glucose); this is shown by the following calculation involving 1.00 gram of stearic acid and 1.00 gram of glucose. 1.00 g stearic acid  a

1 mole stearic acid 120 moles ATP ba b  0.423 mole ATP 284 g stearic acid 1 mole stearic acid

1.00 g glucose  a

1 mole glucose 30 moles ATP ba b  0.167 mole ATP 180 g glucose 1 mole glucose

The fact that fatty acids (stearic acid) yield 2.5 times as much energy per gram as carbohydrates (glucose) means that, in terms of calories consumed, the former “do 2.5 times as much damage” to a person on a diet. In dietary considerations, nutritionists say that 1 gram of carbohydrate equals 4 kcal and that 1 gram of fat equals 9 kcal. We now know the basis for these numbers. The value of 9 kcal for fat takes into account the fact that not all fatty acids present in fat contain 18 carbon atoms (the basis for our preceding calculations) and also the fact that fats contain glycerol, which produces ATP when degraded. Is the preferred fuel for “running” the human body fatty acids, which yield 2.5 times as much energy per gram as glucose, or is it glucose? In a normally functioning human body, certain organs use both fuels, others prefer glucose, and still others prefer fatty acids. Here are some generalizations about “fuel” use: 1. Skeletal muscle uses glucose (from glycogen) when in an active state. In a resting state, it uses fatty acids. 2. Cardiac muscle depends first on fatty acids and secondarily on ketone bodies (Section 25.6), glucose, and lactate. 3. The liver uses fatty acids as the preferred fuel. 4. Brain function is maintained by glucose and ketone bodies (Section 25.6). Fatty acids cannot cross the blood–brain barrier and thus are unavailable.

25.6 KETONE BODIES

Ketone bodies are produced when the amount of acetyl CoA is excessive compared with the amount of oxaloacetate available to react with it (Step 1 of the citric acid cycle).

Ordinarily, when there is adequate balance between lipid and carbohydrate metabolism, most of the acetyl CoA produced from the b-oxidation pathway is further processed through the citric acid cycle. The first step of the citric acid cycle (Section 23.6) involves the reaction between oxaloacetate and acetyl CoA. Sufficient oxaloacetate must be present for the acetyl CoA to react with. Oxaloacetate concentration depends on pyruvate produced from glycolysis (Section 24.2); pyruvate can be converted to oxaloacetate by pyruvate carboxylase (Section 24.6). Certain body conditions upset the lipid–carbohydrate balance required for acetyl CoA generated by fatty acids to be processed by the citric acid cycle. These conditions include (1) dietary intake high in fat and low in carbohydrates, (2) diabetic conditions where the body cannot adequately process glucose even though it is present, and (3) prolonged fasting conditions, including starvation, where glycogen supplies are exhausted. Under these conditions, the problem of inadequate oxaloacetate supplies arises, which is compounded by the body’s using oxaloacetate that is present to produce glucose through gluconeogenesis (Section 24.6). What happens when oxaloacetate supplies are too low for all acetyl CoA present to be processed through the citric acid cycle? The excess acetyl CoA is diverted to the formation of ketone bodies. A ketone body is one of three substances (acetoacetate, b-hydroxybutyrate, and acetone) produced from acetyl CoA when an excess of acetyl CoA from fatty acid degradation accumulates because of triacylglycerol–carbohydrate metabolic imbalances. The structural formulas for the three ketone bodies, two of which are C4 molecules and the other a C3 molecule, are

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25.6 Ketone Bodies

B

CH3 A CHO OH A CH2 A COO⫺

CH3 A C O A CH3 B

CH3 A C O A CH2 A COO⫺

855

Acetoacetate

␤ -Hydroxybutyrate

Acetone

C4 ketoacid

C4 hydroxyacid

C3 ketone

Chemically, these three structures are closely related. The relationships are most easily seen if the focus starts with the molecule acetoacetate. 1. Reduction of the ketone group present in acetoacetate to a secondary alcohol produces b-hydroxybutyrate. Such a reduction process was initially considered in Section 15.10. B

CH3 Reducing A agent C O A CH2 NADH/H⫹ NAD⫹ A ⫺ COO

CH3 A CHO OH A CH2 A COO⫺

␤ -Hydroxybutyrate

Acetoacetate

Structurally, there is no ketone functional group present in b-hydroxybutyrate. Despite it not being a ketone, it is still called a ketone body because of its structural relationship to acetoacetate. 2. Decarboxylation of acetoacetate produces acetone. CH3 A C O ⫹ CO2 A CH3 B

B

CH3 DecarboxyA lation C O A CH2 H⫹ A ⫺ COO

Acetone

Acetoacetate

For a number of years, ketone bodies were thought of as degradation products that had little physiological significance. It is now known that ketone bodies can serve as sources of energy for various tissues and are very important energy sources in heart muscle and the renal cortex. Even the brain, which requires glucose, can adapt to obtain a portion of its energy from ketone bodies in dieting situations that involve a properly constructed low-carbohydrate diet. For each of the following structural characterizations for ketone bodies identify the ketone body to which it applies. There may be more than one correct answer for a given characterization. a. b. c. d.

It is a C4 molecule. It is a ketoacid. It can be produced by reduction of acetoacetate. Its structure contains a ketone functional group.

Solution

a. Acetoacetate and b-hydroxybutyrate. Acetoacetate is a C4 ketoacid and b-hydroxybutyrate is a C4 hydroxyacid. b. Acetoacetate. Both acetoacetate and b-hydroxybutyrate are acids; the first is a ketoacid and the second is a hydroxyacid. c. b-Hydroxybutyrate. Reduction of the ketone functional group in acetoacetate to a secondary alcohol group produces the molecule b-hydroxybutyrate. d. Acetoacetate and acetone. Acetoacetate is a ketoacid and acetone is a simple ketone. (continued)

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Chapter 25 Lipid Metabolism

Practice Exercise 25.5 For each of the following structural characterizations for ketone bodies identify the ketone body to which it applies. There may be more than one correct answer for a given characterization. a. b. c. d.

It is a C3 molecule. It can be produced by decarboxylation of acetoacetate. Its structure contains a carboxyl functional group. It is classified as a ketone body but it is not a ketone.

Answers: a. Acetone; b. Acetone; c. Acetoacetate and b-hydroxybutyrate; d. b-Hydroxybutyrate

Ketogenesis Even when ketogenic conditions are not present in the human body, the liver produces a small amount of ketone bodies.

Ketogenesis is the metabolic pathway by which ketone bodies are synthesized from acetyl CoA. Items to consider about this process prior to looking at the actual steps in this four-step process are: 1. The primary site for the process is liver mitochondria. 2. The first ketone body to be produced is acetoacetate. This production occurs in Step 3 of ketogenesis. 3. Some of the acetoacetate produced in Step 3 is converted to the second ketone body, b-hydroxybutyrate, in Step 4 of ketogenesis. 4. The acetoacetate and b-hydroxybutyrate synthesized by ketogenesis in the liver are released to the bloodstream where acetone, the third ketone body, is produced. 5. Acetoacetate is somewhat unstable and can spontaneously or enzymatically lose its carboxyl group to form acetone. Thus, the ketone body acetone is not actually a product of the metabolic pathway ketogenesis. 6. The ketone body acetone present in the bloodstream is a volatile substance that is mainly excreted by exhalation. Its sweet odor is detectible in the breath of a diabetic. 7. The amount of acetone present is usually small compared to the concentrations of the other two ketone bodies. The actual reaction steps in the process of ketogenesis are: Step 1:

First condensation. Ketogenesis begins as two acetyl CoA molecules combine to produce acetoacetyl CoA, a reversal of the last step of the b-oxidation pathway (Section 25.4). O O B B CH3 OCO S O CoA  CH3 OCO S O CoA Acetyl CoA

Thiolase

Acetyl CoA

O O B B CH3 O CO CH2 OCO S O CoA  CoAO SH Acetoacetyl CoA

Step 2:

Second condensation. Acetoacetyl CoA then reacts with a third acetyl CoA and water to produce 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) and CoA—SH. O O O B B B CH3 OCO CH2 O CO S O CoA  CH3 O C O S O CoA  H2O Acetoacetyl CoA

HMG-CoA synthase

Acetyl CoA

OH O A B OOCO CH2 O COCH2 O CO S O CoA  CoAOSH  H A CH3



HMG-CoA

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25.6 Ketone Bodies

857

Step 3: Chain cleavage. HMG-CoA is then cleaved to acetyl CoA and acetoacetate. OH O A B  OOCO CH2 O COCH2 OC O S O CoA A CH3

HMG-CoA lyase

HMG-CoA

O O B B OOCOCH2 O COCH3  CH3 OC O S O CoA



Acetoacetate

Acetyl CoA

Step 4: Reduction. Acetoacetate is reduced to b-hydroxybutyrate. The reducing agent is

NADH. O ␤-Hydroxybutyrate B dehydrogenase OOC OCH2O C O CH3



Acetoacetate

NADH/H

OH A OOC OCH2O CHO CH3



NAD

 -Hydroxybutyrate

The four chemical reactions associated with ketogenesis are summarized diagrammatically in Figure 25.8.

Energy Production from Acetoacetate Heart muscle and the renal cortex use acetoacetate in preference to glucose. The brain adapts to the utilization of acetoacetate with starvation or diabetes. 75% of the fuel needs of the brain are obtained from acetoacetate during prolonged starvation.

The ketone bodies b-hydroxybutyrate and acetoacetate are connected by a reversible reaction. Using a different enzyme than used in ketogenesis, b-hydroxybutyrate can be converted back to acetoacetate when cellular energy needs require it. For acetoacetate to be used as a fuel—in heart muscle, for example—it must first be activated. Acetoacetate is activated by transfer of a CoA group from succinyl CoA (a citric acid cycle intermediate). The resulting acetoacetyl CoA is then cleaved to give two acetyl CoA molecules that can enter the citric acid cycle (see Figure 25.9). In effect, acetoacetate is a water-soluble, transportable form of acetyl units.

Ketosis Under normal metabolic conditions (an appropriate glucose–fatty acid balance), the concentration of ketone bodies in the blood is very low—about 1 mg/100 mL. Abnormal

Figure 25.8 Ketogenesis involves the production of ketone bodies from acetyl CoA.

Acetyl CoA

Step 1

+

Acetoacetyl CoA

Acetyl CoA CoA

SH

Acetyl CoA + H2O Step 2 CoA

SH + H+

3-hydroxy-3-methylglutaryl CoA Step 3

Acetyl CoA

Step 4

␤ -Hydroxybutyrate

Acetoacetate

NAD+

NADH/H+

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Figure 25.9 The pathway for utilization of acetoacetate as a fuel. The required succinyl CoA comes from the citric acid cycle.

O

O –

CH3 C CH2 COO Acetoacetate

–

OOC

CH2 CH2 C Succinyl CoA

S

CoA

Succinyl CoA transferase

O CH3

HS

O

–

C CH2 C S Acetoacetyl CoA CoA

OOC

CH2

CH2

COO–

Succinate

Thiolase

O CH3 C S CoA Acetyl CoA

CoA

O CH3

C S CoA Acetyl CoA

metabolic conditions, such as those mentioned at the start of this section, produce elevated blood ketone levels, levels 50–100 times greater than normal. Excess accumulation of ketone bodies in blood (20 mg/100 mL) is called ketonemia. At a level of 70 mg/100 mL, the renal threshold is exceeded, and ketone bodies are excreted in the urine, a condition called ketonuria. The overall accumulation of ketone bodies in the blood and urine is called ketosis. Ketosis is often detectable by the smell of acetone on a person’s breath; acetone is very volatile and is excreted through the lungs. For the vast majority of persons following a low-carbohydrate diet, the effects of ketosis appear to be harmless or nearly so. The symptoms of the mild ketosis that occurs as the result of such dieting include headache, dry mouth, and sometimes foul-smelling breath. Two of the three ketone bodies—acetoacetate and b-hydroxybutyrate—are acids. Their presence in blood causes a slight but significant decrease in blood pH. This can result in acidosis (Section 10.12) in severe ketosis situations. Symptoms include heavy breathing (because acidic blood can carry less oxygen) and increased urine output that can lead to dehydration. Ultimately, the condition can cause coma and death. Acidosis from elevated ketone body levels is often called keto acidosis or metabolic acidosis to distinguish it from respiratory acidosis (Section 10.12), which is not linked to ketone bodies.

25.7 BIOSYNTHESIS OF FATTY ACIDS: LIPOGENESIS Lipogenesis is the metabolic pathway by which fatty acids are synthesized from acetyl CoA. As was the case for the opposing processes of glycolysis and gluconeogenesis, lipogenesis is not simply a reversal of the steps for degradation of fatty acids (the b-oxidation pathway). Before we look at the details of fatty acid synthesis, we will consider some differences between the synthesis and degradation of fatty acids. 1. Lipogenesis occurs in the cell cytosol, whereas degradation of fatty acids occurs in the mitochondrial matrix. Because they have different reaction sites, these two opposing processes can occur at the same time when necessary.

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2. Different enzymes are involved in the two processes. Lipogenesis enzymes are collected into a multienzyme complex called fatty acid synthase. This enzyme complex ties the reaction steps of lipogenesis closely together. The enzymes involved in fatty acid degradation are not physically associated, so the reaction steps are independent. 3. Intermediates of the two processes are covalently bonded to different carriers. The carrier for fatty acid degradation intermediates is CoA. Lipogenesis intermediates are bonded to ACP (acyl carrier protein). 4. Fatty acid synthesis is dependent on the reducing agent NADPH. Fatty acid degradation is dependent on the oxidizing agents FAD and NAD. 5. Fatty acids are built up two carbons at a time during synthesis and are broken down two carbons at a time during degradation. The source of the two carbon units differs between the two processes. In lipogenesis, acetyl CoA is used to form malonyl ACP, which becomes the carrier of the two carbon units. CoA derivatives are involved in all steps of fatty acid degradation. In general, fatty acid biosynthesis (lipogenesis) occurs any time dietary intake provides more nutrients than are needed for energy requirements. The primary lipogenesis sites are the liver, adipose tissue, and mammary glands. The mammary glands show increased synthetic activity during periods of lactation.

The Citrate–Malate Shuttle System Acetyl CoA is the starting material for lipogenesis. Because acetyl CoA is generated in mitochondria and lipogenesis occurs in the cytosol, the acetyl CoA must first be transported to the cytosol. It exits the mitochondria through a transport system that involves citrate ion. The outer mitochondrial matrix is freely permeable to acetyl CoA, as well as many other substances such as citrate, malate, and pyruvate. The inner mitochondrial membrane, however, is not permeable to acetyl CoA. An indirect shuttle system involving citrate solves this problem. This shuttle system, which is diagrammed in Figure 25.10, functions as follows. Mitochondrial acetyl CoA reacts with oxaloacetate (the first step of the citric acid cycle; Section 23.6) to produce citrate, which is then transported through the inner mitochondrial membrane by a citrate transporter (a membrane protein structure). Once in the cytosol, the citrate undergoes the reverse reaction to its formation to regenerate the acetyl CoA and oxaloacetate, with ATP involved in the process. The acetyl CoA so generated becomes the “fuel” for lipogenesis; the oxaloacetate so generated reacts further to produce malate, in an NADH dependent change. The malate reenters the mitochondrial matrix through a malate transporter, and is then converted to oxaloacetate, which can then react with another acetyl CoA molecule to form citrate and the shuttle process repeats itself. Additional particulars about the shuttle system are found in Figure 25.10. Compared to the carnitine shuttle system for long-chain fatty acid groups (acyl groups; Figure 25.6), the citrate–malate shuttle system is more complex. However, the intermediates in the shuttle have been encountered before, in glycolysis and the citric acid cycle.

ACP Complex Formation Studies show that all intermediates in fatty acid biosynthesis (lipogenesis) are bound to acyl carrier proteins (ACP9SH) rather than coenzyme A (CoA9SH). This applies even to the C2 acetyl group. An acyl carrier protein can be regarded as a “giant coenzyme A molecule.” Involved in the ACP structure are the 2-ethanethiol and pantothenic acid components present in CoA9SH (Section 23.3), which are attached to a polypeptide chain containing 77 amino acid residues.

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Figure 25.10 The citrate–malate

Acetyl CoA

NADH + H+

Mitochondrial matrix

shuttle system for transferring acetyl CoA from a mitochondrion to the cytosol.

Oxaloacetate

NAD+

Inner mitochondrial membrane

CoA

Malate

Citrate

Malate transporter

Outer mitochondrial membrane

SH

Citrate transporter

Malate

Citrate CoA

NAD+ NADH + H

SH

ATP

Oxaloacetate +

ADP + Pi Acetyl CoA

Fatty acid biosynthesis (lipogenesis)

Cytosol

Two simple ACP complexes are needed to start the lipogenesis process. They are acetyl ACP, a C29ACP, and malonyl ACP, a C39ACP. Additional malonyl ACP molecules are needed as the lipogenesis process proceeds. Cytosolic acetyl CoA is the starting material for the production of both of these simple ACP complexes. Acetyl ACP is produced by the direct reaction of acetyl CoA with an ACP molecule. O B CH3 OCO S O CoA  ACPO S O H Acetyl CoA

The parent compound for the malonyl group is malonic acid, the C3 dicarboxylic acid.

O B CH3 OCO S OACP  CoAO S O H

Acetyl transferase

ACP

Acetyl ACP

CoA

The reaction to produce malonyl ACP requires two steps. The first step is a carboxylation reaction with ATP involvement.

O O B B HOO CO CH2 OCOOH

O B CH3 OCO S O CoA  CO2

O O B B OOCO CH2 O CO S O CoA

Acetyl CoA carboxylase

Acetyl CoA ATP



ADP  Pi

Malonyl CoA

This reaction occurs only when cellular ATP levels are high. It is catalyzed by acetyl CoA carboxylase complex, which requires both Mn2 ion and the B vitamin biotin for its activity. The malonyl CoA so produced then reacts with ACP to produce malonyl ACP. O O B B OOCO CH2 OCOS O CoA  ACPO S O H



Malonyl CoA

ACP

Malonyl transferase

O O B B OOCOCH2 OCOS OACP  CoAO S O H



Malonyl ACP

CoA

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Figure 25.11 In the first "turn" of the

Acetyl ACP

fatty acid biosynthetic pathway, acetyl ACP is converted to butyryl ACP. In the next cycle (not shown), the butyryl ACP reacts with another malonyl ACP to produce a 6-carbon acid. Continued cycles produce acids with 8, 10, 12, 14, and 16 carbon atoms.

1

+

Condensation

861

Malonyl ACP

ACP + CO2 Acetoacetyl ACP

NADPH/H+ 2

Hydrogenation

NADP+ ␤ -Hydroxybutyryl ACP

3

Dehydration

H2O Crotonyl ACP

NADPH/H+ 4

Hydrogenation

NADP+ Butyryl ACP

Chain Elongation Four reactions that occur in a cyclic pattern within the multienzyme fatty acid synthase complex constitute the chain elongation process used for fatty acid synthesis. The reactions of the first turn of the cycle, in general terms, are shown in Figure 25.11. Specific details about this series of reactions follow. Step 1: Condensation. Acetyl ACP and malonyl ACP condense together to form

acetoacetyl ACP. O O O B B B  CH3 OCOSOACP  OOCO CH2 OCOSOACP Acetyl ACP

O O B B CH3 O CO CH2 OCOSOACP  CO2  ACP OSH

Malonyl ACP

Acetoacetyl ACP

Note that a C2 species (acetyl) and a C3 species (malonyl) react to produce a C4 species (acetoacetyl) rather than a C5 species. One carbon atom leaves the reaction in the form of a CO2 molecule. Steps 2 through 4 involve a sequence of functional group changes that we have encountered twice before—in fatty acid degradation (Section 25.4) and in the citric acid cycle (Section 23.6). This time, however, the changes occur in the reverse sequence to that previously encountered. The functional group changes are 2 Reduction

3

4

secondary Dehydration Reduction Ketone 888888888n 88888888n alkene 8888888888n alkane (hydrogenation) (hydrogenation) alcohol Step 2:

First hydrogenation. The keto group of the acetoacetyl complex, which involves the b-carbon atom, is reduced to the corresponding alcohol by NADPH.

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OH O A B CH3 OCHO CH2 OCOS OACP

O O B B CH3 O COCH2 O COS OACP Acetoacetyl ACP

Step 3: Steps 2, 3, and 4 of fatty acid biosynthesis accomplish the reverse of Steps 3, 2, and 1 of the b-oxidation pathway.

NADPH/H NADP

Dehydration. The alcohol produced in Step 2 is dehydrated to introduce a double bond into the molecule (between the a and b carbons). O OH A B CH3 O CHOCH2 O COS OACP  -Hydroxybutyryl ACP

Step 4:

O B CH3 OCH P CHO COS OACP trans

Crotonyl ACP

H2O

Second hydrogenation. The double bond introduced in Step 3 is converted to a single bond through hydrogenation. As in Step 2, NADPH is the reducing agent. O B CH3 OCH P CHO COS OACP

O B CH3 O CH2 OCH2 O COS OACP

trans

Crotonyl ACP

Among enzymes, the multienzyme complex fatty acid synthase is considered to be a “monster” or “gargantuan” enzyme in terms of size. Recent research relating to a fungal fatty acid synthase indicates that the enzyme has two reaction chambers with three full sets of active sites, so six fatty acids can be synthesized simultaneously. ACP shuttles intermediates around the reaction chamber and the fatty acid chain length increases by two carbons with each cycle.

 -Hydroxybutyryl ACP

Butyryl ACP

NADPH/H NADP

Further cycles of the preceding four-step process convert the four-carbon acyl group to a six-carbon acyl group, then to an eight-carbon acyl group, and so on (see Figure 25.12). Elongation of the acyl group chain through this procedure, which is tied to the fatty acid synthase complex, stops upon formation of the C16 acyl group (palmitic acid). Different enzyme systems and different cellular locations are required for elongation of the chain beyond C16 and for introduction of double bonds into the acyl group (unsaturated fatty acids). A relatively large input of energy is needed to biosynthesize a fatty acid molecule, as can be seen from the data in Table 25.2, which gives a net summary of the reactants and products involved in the synthesis of one molecule of palmitic acid, the 16:0 fatty acid.

Figure 25.12 The sequence of

O

cycles needed to produce a C16 fatty acid from acetyl ACP. Each loop represents one cycle.

CH3

C S ACP Acetyl ACP

CO2

O CH3

CH2 CH2 C S C4 Fatty acid

ACP Malonyl ACP CO2

O CH3

CH2

CH2 CH2 CH2 C6 Fatty acid

C

Malonyl ACP

ACP

S

Malonyl ACP CO2 Cycle repeats Malonyl ACP

O CH3

(CH2 )14 C O– C16 Fatty acid

CO2

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In which step (of Steps 1 through 4) and in which cycle (first or second turn) of fatty acid biosynthesis (lipogenesis) is each of the following compounds encountered as a product? a.

OH O A B CH3O CH2O CH2O CHOCH2 OC O S O ACP O b. B CH3OCHPCHOC O S OACP O O c. B B CH3 OC O CH2O CO S O ACP d. O B CH3 OCH2 OCH2 OCH2 OCH2 OC O S O ACP Solution

All intermediates produced during the first turn of the cycle will have a C4 carbon chain, those produced during the second turn a C6 carbon chain, those during the third turn a C8 carbon chain, and so on. Determination of which step in a turn is involved is based on the functional group present in the carbon chain. Step 1 produces a keto acid chain, Step 2 a hydroxy acid chain, Step 3 an unsaturated acid chain, and Step 4 a saturated acid chain. a. The characterization for this molecule’s carbon chain is C6 hydroxyacid. The hydroxyacid designation indicates Step 2 and the C6 chain length indicates second turn. b. The carbon chain is a C4 unsaturated acid; this indicates Step 3 and first turn. c. The carbon chain is a C4 keto acid; this indicates Step 1 and first turn. d. The carbon chain is a C6 saturated acid; this indicates Step 4 and second turn.

Practice Exercise 25.6 In which step (of Steps 1 through 4) and in which cycle (first or second turn) of fatty acid biosynthesis (lipogenesis) is each of the following compounds encountered as a product? a.

TABLE 25.2 Reactants and Products in the Biosynthesis of One Molecule of Palmitic Acid, the 16:0 Fatty Acid Reactants

Products

8 acetyl CoA 7 ATP 14 NADPH 6 H

1 palmitate 8 CoA 7 ADP 7 Pi 14 NADP 6 H2O

O O B B CH3 OCH2 OCH2 OC O CH2OCO S O ACP O b. B CH3 OCH2 OCH2 OC O S O ACP O c. B CH3O CH2O CH2O CHPCHOC O S OACP OH O d. A B CH3O CHOCH2 OC O S O ACP Answers: a. Step 1, second turn; b. Step 4, first turn; c. Step 3, second turn; d. Step 2, first turn

Unsaturated Fatty Acid Biosynthesis Production of unsaturated fatty acids (insertion of double bonds) requires molecular oxygen (O2). In an oxidation step, hydrogen is removed and combined with the O2 to form water.

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H H O A A B RO COCO (CH2)n O COO  O2 A A H H

NADPH/H NADP

O B RO CPCO (CH2)n OCOO  2H2O A A H H

In humans and animals, enzymes can introduce double bonds only between C-4 and C-5 and between C-9 and C-10. Thus the important unsaturated fatty acids linoleic (C18 with C-9 and C-12 double bonds) and linolenic (C18 with C-9, C-12, and C-15 double bonds) cannot be biosynthesized. They must be obtained from the diet. (Plants have the enzymes necessary to synthesize these acids.) Acids such as linoleic and linolenic (Section 19.2), which cannot be synthesized by the body but are necessary for its proper functioning, are called essential fatty acids. Lipogenesis can be used to convert glucose to fatty acids via acetyl CoA. The reverse process, conversion of fatty acids to glucose, is not possible within the human body. Fatty acids can be broken down to acetyl CoA, but there is no enzyme present for the conversion of acetyl CoA to pyruvate or oxaloacetate, starting materials for gluconeogenesis (Section 24.6). Plants and some bacteria do possess the needed enzymes and thus can convert fatty acids to carbohydrates.

25.8 RELATIONSHIPS BETWEEN LIPOGENESIS AND CITRIC ACID CYCLE INTERMEDIATES The intermediates in the last four steps of the citric acid cycle are all C4 molecules (Section 23.6). In the first cycle of the four repetitive reactions in lipogenesis all of the carbon chains attached to ACP are C4 chains. Several relationships exist between these two sets of C4 entities. The last four intermediates of the citric acid cycle bear the following relationship to each other. Saturated C4 diacid S unsaturated C4 diacid S hydroxy C4 diacid S keto C4 diacid The intermediate C4 carbon chains of lipogenesis bear the following relationship to each other. Keto C4 monoacid S hydroxy C4 monoacid S unsaturated C4 monoacid S saturated C4 monoacid Note two important contrasts in these compound sequences: 1. The citric acid intermediates involve C4 diacids and the lipogenesis intermediates involve C4 monoacids. 2. The order in which the various acid derivative types are encountered in lipogenesis is the reverse of the order in which they are encountered in the citric acid cycle. Figure 25.13 contrasts the structures of the various C4 diacid intermediates from the citric acid cycle with the various C4 monoacid intermediates encountered in lipogenesis.

25.9 BIOSYNTHESIS OF CHOLESTEROL So far in this chapter, our discussion of lipid metabolism has focused on fats and oils (triacylglycerols) and their hydrolysis products, fatty acids and glycerol. We now consider another very important lipid—cholesterol.

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25.9 Biosynthesis of Cholesterol

Lipogenesis Intermediates

CH3

Acetoacetate

Keto derivative

BUTYRATE CH2 CH2 COO–

O CH3 C

OH CH3

CH

CH2

C

C

–

OOC

CH2 CH2 COO

O –

4-Carbon diacid (saturated acid)

C

COO–

CH2

Malate

Hydroxy derivative

–

OOC

OH –

OOC

CH

CH2

COO–

Fumarate

Unsaturated derivative

Intermediate in lipogenesis

Intermediate in lipogenesis

H

Oxaloacetate

Keto derivative

Intermediate in lipogenesis

COO

COO–

H CH3

SUCCINATE

–

Crotonate

Unsaturated derivative

Citric Acid Cycle Intermediates

COO

β-Hydroxybutyrate

Hydroxy derivative

4-Carbon monoacid (saturated acid)

CH2

–

865

COO–

H C –

OOC

C H

Intermediate in the citric acid cycle Intermediate in the citric acid cycle Intermediate in the citric acid cycle

Figure 25.13 Structural relationships between C4 citric acid cycle intermediates and C4 lipogenesis intermediates. C4 citric acid cycle intermediates are diacid derivatives and C4 lipogenesis intermediates are monoacid derivatives. The same derivative types are present in both series of intermediates.

Every membrane of every cell in the body has cholesterol as a necessary component. This substance is also the precursor for bile salts, sex hormones, and adrenal hormones (Sections 19.11 and 19.12). In today’s health-conscious world, dietary intake of cholesterol is of great interest because of correlations between high serum cholesterol levels and coronary heart disease. Average daily dietary intake of cholesterol is approximately 0.3 gram. This amount, though important, is small compared to the 1.5–2.0 grams of cholesterol that the body synthesizes every day from acetyl CoA units. The biosynthesis of cholesterol, a C27 molecule, occurs primarily in the liver. Its production consumes 18 molecules of acetyl CoA and involves at least 27 separate enzymatic steps. An overview of cholesterol synthesis is given in Figure 25.14.

Figure 25.14 An overview of the biosynthetic pathway for cholesterol synthesis.

Acetyl CoA C2

Several steps

Mevalonate C6

Several steps

Isopentenyl pyrophosphate C5 Several steps

Cholesterol Multiring C27

Several steps

Lanosterol Multiring C30

Several steps

Squalene Acyclic C30

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The “parent” compound for mevalonate ion is mevalonic acid (3,5-dihydroxy-3-methylpentanoic acid).

In the first phase of cholesterol synthesis, three molecules of acetyl CoA are condensed into a C6 mevalonate ion. O B 3C H3 O CO S OCoA

CH3 O A B CH2 OCH2 OCO CH2O COOH A A OH OH

Acetyl CoA

Several steps

COO A CH2 A HOO COCH3 A CH2 A CH2OH Mevalonate

The C6 mevalonate undergoes a decarboxylation to yield a C5 isoprene derivative called isopentenyl pyrophosphate and CO2. Three ATP molecules are needed in accomplishing this process. COO A CH2 A HOOCOCH3 A CH2 A CH2OH

Several steps

Mevalonate

B

F

Compounds whose structures are based on the five-carbon isoprene unit are called terpenes (Section 13.7).

CH2 B CO CH3 A CH2 A CH2OO P O P Isopentenyl pyrophosphate

The isoprene structural unit (Section 13.7), present in isoprene derivatives in a modified form, is a commonly used five-carbon building block in biosynthetic processes. The next stage of cholesterol biosynthesis involves the condensation of six isoprene units to give the C30 squalene molecule. CH3 CH3 CH3 CH3 A A A A H3COCPCHO CH2 O (CH2 OCPCHO CH2)2 O (CH2 OCHPCO CH2)2 O CH2 O CHP COCH3 Squalene

A “redrawing” of the squalene structure, with numerous twists and bends in it, is helpful in visualizing the next stage of cholesterol biosynthesis, the formation of the four-ring steroid nucleus (Section 19.12) associated with lanosterol (and cholesterol).

Several steps

HO Squalene

Lanosterol

The multistep squalene-to-lanosterol transition involves the formation of four ring systems, a decrease in double bonds from six to two, the migration of two methyl groups to new locations, and the addition of an —OH group to the C30 system. Addition of the —OH group requires the use of molecular oxygen; the O of the —OH group comes from the molecular O2. The transition from lanosterol to cholesterol involves removal of three methyl groups (C30 to C27), reduction of the double bond in the side chain, and migration of the other double bond to a new location.

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Several steps

HO

HO Lanosterol (C30)

c

Cholesterol (C27)

HEMICAL

onnections

Statins: Drugs That Lower Plasma Levels of Cholesterol

Over half of all deaths in the United States are directly or indirectly related to heart disease, in particular to atherosclerosis. Atherosclerosis results from the buildup of plaque (fatty deposits) on the inner walls of arteries. Cholesterol, obtained from lowdensity-lipoproteins (LDL) that circulate in blood plasma, is also a major component of plaque. Because most of the cholesterol in the human body is synthesized in the liver, from acetyl CoA, much research has focused on finding ways to inhibit its biosynthesis. The rate-determining step in cholesterol biosynthesis involves the conversion of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, a process catalyzed by the enzyme HMG-CoA reductase. H3C HO

H3C

COO HMG-CoA reductase

O

After years of testing, the statins are now available as prescription drugs for lowering blood cholesterol levels. Clinical studies indicate that use of these drugs lowers the incidence of heart disease in individuals with mildly elevated blood cholesterol levels. A later-generation statin with a ring structure distinctly different from that of earlier statins—atorvastatin (Lipitor)—became the most prescribed medication in the United States in the year 2000. Note the structural resemblance between part of the structure of Lipitor and that of mevalonate. H3C HO

OH Mevalonate

COO

HO

H HO

OH Mevalonate

SCoA

COO OH

CH3 CH3

3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA)

O

In 1976, as the result of screening more than 8000 strains of microorganisms, a compound now called mevastatin—a potent inhibitor of HMG-CoA reductase—was isolated from culture broths of a fungus. Soon thereafter, a second, more active compound called lovastatin was isolated. H HO

COO OH

O B O H3C R1

COO

H

CH3

R2 R1  R2  H, mevastatin R1  , R2  CH3, lovastatin (Mevacor) R1  R2  CH3, simvastatin (Zocor)

These “statins” are very effective in lowering plasma concentrations of LDL by functioning as competitive inhibitors of HMGCoA reductase.

N H

N

F Atorvastatin (Lipitor)

Recent research studies have unexpectedly shown that the cholesterol-lowering statins have two added benefits. Laboratory studies with animals indicate that statins prompt growth of cells to build new bone, replacing bone that has been leached away by osteoporosis (“brittle-bone disease”). A retrospective study of osteoporosis patients who also took statins shows evidence that their bones became more dense than did bones of osteoporosis patients who did not take the drugs. Statins have also been shown to function as antiinflammatory agents that counteract the effects of a common virus, cytomegalovirus, which is now believed to contribute to the development of coronary heart disease. Researchers believe that by age 65, more than 70% of all people have been exposed to this virus. The virus, along with other infecting agents in blood, may actually trigger the inflammation mechanism for heart disease.

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Interrelationships Between Carbohydrate and Lipid Metabolism Fats from food intake

Carbohydrates from food intake

DIGESTION

DIGESTION

Cell membrane

Triacylglycerols

Fatty acids

LIPOGENESIS

Glycerol

Cholesterol

Glucose

GLYCOLYSIS

Pyruvate

Acetyl CoA

Cytosol

GLUCONEOGENESIS

Mitochondrial membrane

Fatty acids

β-OXIDATION PATHWAY

Pyruvate

Acetyl CoA

KETOGENESIS

Ketone bodies to other tissues

Ketone bodies

CITRIC ACID CYCLE

Interior of mitochondrion

ELECTRON TRANSPORT CHAIN

ATP

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Concepts to Remember

Figure 25.15 Biosynthetic

869

Cholesterol C27

relationships among steroid hormones.

Progestins C21

Glucocorticoids C21

Mineralocorticoids C21

Androgens C19

Estrogens C18

Once cholesterol has been formed, biosynthetic pathways are available to convert it to each of the five major classes of steroid hormones: progestins, androgens, estrogens, glucocorticoids, and mineralocorticoids (see Figure 25.15), as well as to bile acids and vitamin D (Section 21.13).

25.10 RELATIONSHIPS BETWEEN LIPID AND CARBOHYDRATE METABOLISM Acetyl CoA is the primary link between lipid and carbohydrate metabolism. As shown in the Chemistry at a Glance feature on page 868, acetyl CoA is the degradation product for glucose, glycerol, and fatty acids, and it is also the starting material for the biosynthesis of fatty acids, cholesterol, and ketone bodies. Note the four possible fates of acetyl CoA produced from fatty acid, glycerol, and glucose degradation processes. 1. Oxidation in the citric acid cycle. Both lipids (fatty acids and glycerol) and carbohydrates (glucose) supply acetyl CoA for the operation of this cycle. 2. Ketone body formation. This process is of major importance when there is imbalance between lipid and carbohydrate metabolic processes. The imbalance is caused by inadequate glucose metabolism during times of adequate lipid metabolism. 3. Fatty acid biosynthesis. The buildup of excess acetyl CoA when dietary intake exceeds energy needs leads to accelerated fatty acid biosynthesis. 4. Cholesterol biosynthesis. As with fatty acid biosynthesis, cholesterol biosynthesis occurs primarily when the body is in an acetyl CoA–rich state.

c

O N C E P TS TO R E M E M B E R

Triacylglycerol digestion and absorption. Triacylglycerols are digested (hydrolyzed) in the intestine and then reassembled after passage into the intestinal wall. Chylomicrons transport the reassembled triacylglycerols from intestinal cells to the bloodstream (Section 25.1). Triacylglycerol storage and mobilization. Triacylglycerols are stored as fat droplets in adipose tissue. When they are needed for energy, enzyme-controlled hydrolysis reactions liberate the fatty acids, which then enter the bloodstream and travel to tissues where they are utilized (Section 25.2). Glycerol metabolism. Glycerol is first phosphorylated and then oxidized to dihydroxyacetone phosphate, a glycolysis pathway intermediate.

Through glycolysis and the common metabolic pathway, the glycerol can be converted to CO2 and H2O (Section 25.3). Fatty acid degradation. Fatty acid degradation is accomplished through the b-oxidation pathway. The degradation process involves removal of carbon atoms, two at a time, from the carboxyl end of the fatty acid. There are four repeating reactions that accompany the removal of each two-carbon unit. A turn of the cycle also produces one molecule each of acetyl CoA, NADH, and FADH2 (Section 25.4). Ketone bodies. Acetoacetate, b-hydroxybutyrate, and acetone are known as ketone bodies. Synthesis occurs mainly in the liver from

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acetyl CoA as a result of excessive fatty acid degradation. During starvation and in unchecked diabetes, the level of ketone bodies in the blood becomes very high (Section 25.6). Fatty acid biosynthesis. Fatty acid biosynthesis, lipogenesis, occurs through the addition of two-carbon units to a growing acyl chain. The added two-carbon units come from malonyl CoA. A multienzyme

k

complex, an acyl carrier protein (ACP), and NADPH are important parts of the biosynthetic process (Section 25.7). Biosynthesis of cholesterol. Cholesterol is biosynthesized from acetyl CoA in a complex series of reactions in which isoprene units are key intermediates. Cholesterol is the precursor for the various classes of steroid hormones (Section 25.9).

EY R E A C T I O N S A N D E Q U AT I O N S

1. Digestion of triacylglycerols (Section 25.1)

4. One cycle of the b-oxidation pathway (Section 25.4)

Lipase

Triacylglycerol ⫹ H2O 88888n fatty acids ⫹ glycerol ⫹ monoacylglycerols 2. Mobilization of triacylglycerols (Section 25.2) Lipase

Triacylglycerol ⫹ 3H2O 88888n 3 fatty acids ⫹ glycerol

5. First turn of lipogenesis (Section 25.7)

3. Glycerol metabolism (Section 25.3)

Glycerol ⫹ ATP ⫹ NAD ⫹

2NADPH/H⫹ 2NADP⫹

Two steps

dihydroxyacetone + ADP + NADH + phosphate

O B R OCH2O CH2OC OS OCoA ⫹ NAD⫹ ⫹ FAD ⫹ CoAOSH O O B B R OCOS OCoA ⫹ CH3O COS OCoA ⫹ NADH ⫹ FADH 2

Acetyl ACP ⫹ malonyl ACP H⫹

butyryl ACP ⫹ ACP ⫹ CO2 ⫹ H2O

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Digestion and Absorption of Lipids (Section 25.1) 25.1 What percent of dietary lipids are triacylglycerols? 25.2 What are the solubility characteristics of triacylglycerols? 25.3 What effect do salivary enzymes have on triacylglycerols? 25.4 What effect do stomach fluids have on triacylglycerols? 25.5 The process of lipid digestion occurs primarily at two sites

within the human body. a. What are the identities of these two sites? b. What is the relative amount of TAG digestion that occurs at each site? c. What type of digestive enzyme functions at each site? 25.6 Why does ingestion of lipids make one feel “full” for a long time? 25.7 What function does bile serve in lipid digestion? 25.8 What are the major products of triacylglycerol digestion? 25.9 Complete hydrolysis of triacylglycerols during digestion is

unusual. Explain.

25.10 What is a fatty acid micelle?

25.17 What role does cAMP play in triacylglycerol mobilization? 25.18 Triacylglycerols in adipose tissue do not enter the bloodstream

as triacylglycerols. Explain.

Glycerol Metabolism (Section 25.3) 25.19 In which step of glycerol metabolism does each of the follow-

ing events occur? a. ATP is consumed. b. A phosphorylation reaction occurs. c. Dihydroxyacetone phosphate is produced. d. Glycerol kinase is active. 25.20 In which step of glycerol metabolism does each of the following events occur? a. The oxidizing agent NAD⫹ is needed. b. ADP is produced. c. Glycerol 3-phosphate is a reactant. d. A secondary alcohol group is oxidized. 25.21 How many ATP molecules are expended in the conversion of

glycerol to a glycolysis intermediate?

25.11 What happens to the products of triacylglycerol digestion after

25.22 What are the two fates of glycerol after it has been converted to

Triacylglycerol Storage and Mobilization (Section 25.2) 25.13 What is the distinctive structural feature of adipocytes? 25.14 What is the major metabolic function of adipose tissue?

25.23 Indicate whether each of the following statements concerning

they pass through the intestinal wall? 25.12 What is a chylomicron, and what is its function?

25.15 What is triacylglycerol mobilization? 25.16 What situation signals the need for mobilization of triacyl-

glycerols from adipose tissue?

a glycolysis intermediate?

Oxidation of Fatty Acids (Section 25.4) the fatty acid activation process that occurs prior to b-oxidation is true or false. a. CoA9SH is a reactant. b. A molecule of ADP is produced. c. The site for the process is the outer mitochondrial membrane. d. Two ATP molecules are consumed.

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Exercises and Problems

25.24 Indicate whether each of the following statements concerning

the fatty acid activation process that occurs prior to b-oxidation is true or false. a. Acetyl CoA is a product. b. A phosphorylation enzyme is needed. c. A molecule of AMP is produced. d. The activation product is acyl CoA.

25.25 Indicate whether each of the following aspects of the carnitine

shuttle system associated with the process of b-oxidation occurs in the mitochondrial matrix or in the mitochondrial intermembrane space. a. Acyl CoA is a reactant. b. Carnitine enters the inner mitochondrial membrane. c. Carnitine is converted to acyl carnitine. d. Free CoA is a reactant. 25.26 Indicate whether each of the following aspects of the carnitine shuttle system associated with the process of b-oxidation occurs in the mitochondrial matrix or in the mitochondrial intermembrane space. a. Acyl CoA is a product. b. Acyl carnitine enters the inner mitochondrial membrane. c. Acyl carnitine is converted to carnitine. d. Coenzyme A is a product. 25.27 Only one molecule of ATP is needed to activate fatty acids

before oxidation occurs, yet in “bookkeeping” on this energy expenditure it is counted as the loss of two ATP molecules. Explain why. 25.28 What is the difference between an acetyl CoA molecule and an acyl CoA molecule? 25.29 Explain what functional group change occurs, during one turn

of the b-oxidation pathway in a. Step 1. b. Step 2. c. Step 3. 25.30 For one turn of the b-oxidation pathway, arrange the following b-carbon functional groups in the order in which they are encountered: secondary alcohol, ketone, alkane, and alkene. 25.31 What is the configuration of the unsaturated enoyl CoA formed

by dehydrogenation during a turn of the b-oxidation pathway?

25.32 What is the configuration of the b-hydroxyacyl CoA formed by

hydration during a turn of the b-oxidation pathway?

25.33 In which step (of Steps 1 through 4) and in which turn (second

or third) of the b-oxidation pathway is each of the following compounds encountered as a reactant if the fatty acid to be degraded is decanoic acid? a. O OH B A CH3O(CH2)4OCHOCH2 OC O S O CoA b. O B CH3O(CH2)2O CHPCHOC O S OCoA O O c. B B CH3O(CH2)2OC O CH2O CO S O CoA d. O B CH3O(CH2)6OC O S O CoA

25.34 In which step (of Steps 1 through 4) and in which turn (second

or third) of the b-oxidation pathway is each of the following compounds encountered as a reactant if the fatty acid to be degraded is decanoic acid?

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O O B B CH3O(CH2)4OC O CH2OCO S O CoA O b. B CH3O(CH2)4OC O S O CoA c. O B CH3O(CH2)4O CHPCHOC O S OCoA OH O d. A B CH3O(CH2)2O CHOCH2 OC O S O CoA a.

25.35 Which compound(s) in Problem 25.33 undergo(es) a dehydro-

genation reaction during a turn of the b-oxidation pathway?

25.36 Which compound(s) in Problem 25.34 undergo(es) a chain-

cleavage reaction during a turn of the b-oxidation pathway?

25.37 How many turns of the b-oxidation pathway would be needed

to degrade each of the following fatty acids to acetyl CoA? a. 16:0 fatty acid b. 12:0 fatty acid 25.38 How many turns of the b-oxidation pathway would be needed to degrade each of the following fatty acids to acetyl CoA? a. 20:0 fatty acid b. 10:0 fatty acid 25.39 The degradation of cis-3-hexenoic acid, a 6:1 acid, requires one

more step than the degradation of hexanoic acid, a 6⬊0 acid. Describe the nature of the extra step. 25.40 The degradation of cis-4-hexenoic acid, a 6:1 acid, requires one more step than the degradation of hexanoic acid, a 6⬊0 acid. Describe the nature of this extra step. ATP Production from Fatty Acid Oxidation (Section 25.5) 25.41 Identify the major fuel for skeletal muscle in

a. an active state. b. a resting state. 25.42 Explain why fatty acids cannot serve as fuel for the brain. 25.43 Consider the conversion of a C10 saturated acid entirely to

acetyl CoA. a. How many turns of the b-oxidation pathway are required? b. What is the yield of acetyl CoA? c. What is the yield of NADH? d. What is the yield of FADH2? e. How many high-energy ATP bonds are consumed? 25.44 Consider the conversion of a C14 saturated acid entirely to acetyl CoA. a. How many turns of the b-oxidation pathway are required? b. What is the yield of acetyl CoA? c. What is the yield of NADH? d. What is the yield of FADH2? e. How many high-energy ATP bonds are consumed? 25.45 What is the net ATP production for the complete oxidation to

CO2 and H2O of the fatty acid in Problem 25.43? 25.46 What is the net ATP production for the complete oxidation to CO2 and H2O of the fatty acid in Problem 25.44? 25.47 Which yield more FADH2, saturated or unsaturated fatty

acids? Explain.

25.48 Which yield more NADH, saturated or unsaturated fatty

acids? Explain.

25.49 Compare the energy released when 1 g of carbohydrate and

1 g of lipid are completely degraded in the body.

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Chapter 25 Lipid Metabolism

25.50 Compare the net ATP produced from 1 molecule of glucose

and 1 molecule of hexanoic acid when they are completely degraded in the body.

25.65 What is ketosis? 25.66 Severe ketosis situations produce acidosis. Explain.

Ketone Bodies (Section 25.6) 25.51 What three body conditions are conducive to ketone body formation? 25.52 Why does a deficiency of carbohydrates in the diet lead to ketone body formation?

Biosynthesis of Fatty Acids (Section 25.7) 25.67 Compare the intracellular locations where fatty acid biosynthesis and fatty acid degradation take place. 25.68 How does the structure of fatty acid synthase differ from that of the enzymes that degrade fatty acids?

25.53 What is the relationship between oxaloacetate concentration

25.69 Coenzyme A plays an important role in fatty acid degradation.

and ketone body formation? 25.54 What is the relationship between pyruvate concentration and ketone body formation?

What is its counterpart in fatty acid biosynthesis, and how does its structure differ from that of coenzyme A? 25.70 What does the designation ACP stand for?

25.55 Draw the structures of the three compounds classified as

25.71 Indicate whether each of the following aspects of the citrate–

ketone bodies. 25.56 Two of the three ketone bodies can be formed from the third one. Write equations for the formation of these two compounds.

25.57 Identify the ketone body (or bodies) to which each of the

following statements applies. a. Its structure contains a ketone functional group. b. Its structure contains a hydroxyl functional group. c. It is produced in Step 3 of ketogenesis. d. It is produced from the decomposition of acetoacetate. 25.58 Identify the ketone body (or bodies) to which each of the following statements applies. a. Its structure contains two methyl groups. b. Its structure contains a carboxyl functional group. c. It is produced in step 4 of ketogenesis. d. It is produced from the reduction of acetoacetate. 25.59 Identify the step in ketogenesis to which each of the following

statements applies. a. The first condensation reaction occurs. b. A reduction reaction occurs. c. A C49CoA molecule is produced. d. A C29CoA molecule is produced. 25.60 Identify the step in ketogenesis to which each of the following statements applies. a. The second condensation reaction occurs. b. A chain-cleavage reaction occurs. c. A C69CoA molecule is produced. d. A C4 molecule is converted into another C4 molecule. 25.61 In which step or steps of ketogenesis is/are the following

molecules encountered? a. Acetyl CoA as a reactant b. Acetoacetyl CoA as a reactant c. HMG-CoA as a product d. Acetoacetate as a product 25.62 In which step or steps of ketogenesis is/are the following molecules encountered? a. Acetyl CoA as a product b. Acetoacetyl CoA as a product c. HMG-CoA as a reactant d. Acetoacetate as a reactant 25.63 Before acetoacetate can be used as a “fuel” it must first be

activated. What are the names of the reactants and products in the activation reaction? 25.64 What are the names of the reactants and products in the reaction by which “usable fuel” is produced from the activated form of acetoacetate?

malate shuttle system associated with the process of lipogenesis occurs in the mitochondrial matrix or in the cytosol. a. Citrate is produced from oxaloacetate and acetyl CoA. b. ATP is converted to ADP. c. Acetyl CoA and oxaloacetate are produced from citrate. d. NADH is used as a reducing agent. 25.72 Indicate whether each of the following aspects of the citrate– malate shuttle system associated with the process of lipogenesis occurs in the mitochondrial matrix or in the cytosol. a. Citrate enters the inner mitochondrial membrane. b. Malate is produced from oxaloacetate. c. NAD is used to convert malate to oxaloacetate. d. CoA9SH is generated. 25.73 Indicate whether each of the following lipogenesis events

associated with ACP complex formation applies to (1) acetyl CoA, (2) acetyl ACP, (3) malonyl CoA, or (4) malonyl ACP. a. A carboxylation occurs in its production. b. The enzyme acetyl transferase is needed in its production. c. The B vitamin biotin is involved in its production. d. Acetyl CoA and ACP are the reactants in its production. 25.74 Indicate whether each of the following lipogenesis events associated with ACP complex formation applies to (1) acetyl CoA, (2) acetyl ACP, (3) malonyl CoA, or (4) malonyl ACP. a. Acetyl CoA and CO2 are the reactants in its production. b. The enzyme malonyl transferase is needed in its production. c. ATP is consumed in its production. d. Malonyl CoA and ACP are the reactants in its production. 25.75 For the first cycle of the lipogenesis pathway, identify the step

to which each of the following statements apply. a. First hydrogenation reaction occurs. b. A dehydration reaction occurs. c. Acetoacetyl ACP is a product. d. Crotonyl ACP is a reactant. 25.76 For the first cycle of the lipogenesis pathway, identify the step to which each of the following statements apply. a. Second hydrogenation reaction occurs. b. A condensation reaction occurs. c. Acetoacetyl ACP is a reactant. d. Crotonyl ACP is a product. 25.77 What is the name of the intermediate compound generated in

the first cycle of the lipogenesis pathway that has each of the following characteristis? a. Has a carbon chain that is derived from a C4 keto monoacid b. Has a carbon chain that is derived from a C4 unsaturated monoacid c. Produced by a dehydration reaction d. Produced in a reaction that also produces CO2

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Exercises and Problems

25.78 What is the name of the intermediate compound generated in

the first cycle of the lipogenesis pathway that has each of the following characteristics? a. Has a carbon chain that is derived from a C4 hydroxy monoacid b. Has a carbon chain that is derived from a C4 saturated monoacid c. Undergoes a dehydration reaction d. Produced by a condensation reaction

25.79 Indicate whether each of the following intermediate compounds

generated in the first or second cycle of the lipogenesis pathway is produced by (1) a dehydration reaction, (2) a hydrogenation reaction, or (3) a condensation reaction. a. O O B B CH3O CO CH2O CO S OACP b. OH O A B CH3O CH2O CH2O CHO CH2OCO S OACP O c. B CH3 OCH2 OCH2 OCHP CHOC O S OACP d. O B CH3O CH2O CH2O CO S OACP

25.80 Indicate whether each of the following intermediate compounds

generated in the first or second cycle of the lipogenesis pathway is produced by (1) a dehydration reaction, (2) a hydrogenation reaction, or (3) a condensation reaction. O a. B CH3O CH2O CH2O CH2O CH2OCO S OACP O b. B CH3 OCHP CHOCO S OACP c. OH O A B CH3O CHO CH2OCO S OACP O O d. B B CH3O CH2O CH2O CO CH2OCO S OACP

25.81 What role does molecular oxygen, O2, play in fatty acid

biosynthesis?

25.82 What is the characteristic structural feature of an essential fatty

acid?

25.83 Consider the biosynthesis of a C14 saturated fatty acid from

acetyl CoA molecules. a. How many turns of the fatty acid biosynthetic pathway are needed? b. How many molecules of malonyl ACP must be formed? c. How many high-energy ATP bonds are consumed? d. How many NADPH molecules are needed? 25.84 Consider the biosynthesis of a C16 saturated fatty acid from acetyl CoA molecules. a. How many turns of the fatty acid biosynthetic pathway are needed? b. How many molecules of malonyl ACP must be formed? c. How many high-energy ATP bonds are consumed? d. How many NADPH molecules are needed?

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Relationships Between Lipogenesis and Citric Acid Cycle Intermediates (Section 25.8) 25.85 What is the citric acid cycle diacid intermediate counterpart for each of the following lipogenesis C49ACP monoacid intermediates? a. Butyrate b. Acetoacetate c. b-Hydroxybutyrate d. Crotonate 25.86 What is the lipogenesis C49ACP monoacid intermediate counterpart for each of the following citric acid cycle C4 diacid intermediates? a. Succinate b. Malate c. Oxaloacetate d. Fumarate 25.87 Identify each of the following C4 species as a (1) hydroxy acid,

(2) keto acid, (3) saturated acid, or (4) unsaturated acid. a. Crotonate b. Oxaloacetate c. Acetoacetate d. Malate 25.88 Identify each of the following C4 species as a monocarboxylic acid or dicarboxylic acid. a. Succinate b. Butyrate c. b-Hydroxybutyrate d. Fumarate

Biosynthesis of Cholesterol (Section 25.9) 25.89 Approximately what percent of the total amount of cholesterol in your body is derived from the following? a. Your diet b. Biosynthesis 25.90 What is the starting material for the biosynthesis of cholesterol? 25.91 In each of the following pairs of intermediates in the biosyn-

thetic pathway for cholesterol, specify which one is encountered first in the pathway. a. Mevalonate and squalene b. Isopentenyl pyrophosphate and lanosterol c. Lanosterol and squalene 25.92 In each of the following pairs of intermediates in the biosynthetic pathway for cholesterol, specify which one is encountered first in the pathway. a. Mevalonate and lanosterol b. Isopentenyl pyrophosphate and squalene c. Mevalonate and isopentenyl pyrophosphate 25.93 For each pair of compounds in Problem 25.91, tell whether the

number of carbon atoms in the first compound is less than, the same as, or greater than the number of carbon atoms in the second compound. 25.94 For each pair of compounds in Problem 25.92, tell whether the number of carbon atoms in the first compound is less than, the same as, or greater than the number of carbon atoms in the second compound.

Relationships Between Lipid and Carbohydrate Metabolism (Section 25.10) 25.95 Name three types of compounds for which acetyl CoA, the primary link between lipid and carbohydrate metabolism, is the following. a. Biosynthetic starting material b. Degradation product 25.96 Name four possible fates for the acetyl CoA produced through degradation of carbohydrate and lipid dietary sources.

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Chapter 25 Lipid Metabolism

A DD D IT IO NAL P R O BL L EM S 25.97 With which of these processes, (1) glycerol catabolism,

(2) b-oxidation pathway, (3) lipogenesis, or (4) ketogenesis, is each of the following molecules associated? a. Enoyl CoA b. Malonyl ACP c. Dihydroxyacetone phosphate d. b-Hydroxybutyrate 25.98 With which of these processes, (1) fatty acid catabolism, (2) lipogenesis, (3) ketogenesis, or (4) consumption of molecular O2, is each of the following situations associated? a. Carnitine shuttle system b. Citrate shuttle system c. Conversion of squalene to cholesterol d. Conversion of a saturated fatty acid to an unsaturated fatty acid 25.99 Identify the step (among Steps 1 through 4) of the fatty acid chain elongation process in lipogenesis to which each of the following characterizations applies. a. Malonyl ACP is a reactant. b. CO2 is a product. c. A dehydration reaction occurs. d. A carbon–carbon double bond is converted to a carbon– carbon single bond. 25.100 Indicate in what order the following events occur in the digestion of triacylglycerols (TAGs). (1) Bile emulsifies TAG “droplets.” (2) TAGs incorporated into chylomicrons enter the lymph system. (3) TAGs are hydrolyzed to monoacylglycerols. (4) Free fatty acids are “repackaged” into TAGs.

25.101 Indicate whether each of the following statements is true or false.

a. Chylomicrons are lipoproteins. b. Acetoacetate is an intermediate in the conversion of glycerol to dihydroxyacetone phosphate. c. The molecule carnitine is involved in fatty acid activation. d. One turn of the b-oxidation pathway produces two molecules of ATP. 25.102 Indicate whether each of the following pairings of terms is correct or incorrect as a reactant/product pair for reactions in the b-oxidation pathway. a. Alkene functional group; dehydrogenation b. Ketone functional group; chain cleavage c. Alkane functional group; hydration d. Secondary alcohol functional group; oxidation 25.103 Indicate whether each of the following pairings of terms is correct or incorrect as a reactant/product pair for reactions in the chain elongation phase of lipogenesis. a. Alkene functional group; hydrogenation b. Secondary alcohol group; dehydration c. Ketone group; reduction d. Ketone group; hydrogenation 25.104 Arrange the four molecules (1) glucose, (2) sucrose, (3) C8 unsaturated fatty acid, and (4) C14 unsaturated fatty acid in order of increasing biochemical energy content (ATP production) per mole.

multiple-Choice Practice Test 25.105 Which of the following statements concerning digestion of

25.106

25.107

25.108

25.109

dietary triacylglycerols in adults is correct? a. It begins in the mouth. b. It occurs to a small extent (10%) in the stomach. c. It occurs to a large extent (90%) in the stomach. d. It occurs only in the small intestine. Monoacylglycerols are the predominant constituent in which of the following? a. Fatty acid micelles b. Chylomicrons c. Adipocytes d. Bile The first stage of glycerol metabolism is the two-step conversion of glycerol to dihydroxyacetone phosphate. What is the intermediate in this process? a. Dihydroxyacetone b. Monohydroxyacetone phosphate c. Glycerol 3-phosphate d. 3-phosphoglycerate In the oxidation of fatty acids, what is the molecule that shuttles the activated fatty acid across the inner mitochondrial membrane? a. CoA b. Acetyl CoA c. Carnitine d. Citrate What is the first functional group change that occurs in the b-oxidation pathway? a. Alkane to alkene b. Alkene to 2º alcohol c. Alkane to 2º alcohol d. 2º alcohol to ketone

25.110 Which of the following pairings of terms is correct as a

25.111

25.112

25.113

25.114

reactant/product pair for reactions in the b-oxidation pathway? a. Alkene functional group; dehydrogenation b. Ketone functional group; chain cleavage c. Alkane functional group; hydration d. 2º alcohol functional group; hydrogenation How many turns of the b-oxidation pathway are needed to “process” a C16 fatty acid molecule? a. Seven b. Eight c. Fourteen d. Sixteen Which of the following compounds is a ketone body? a. Carnitine b. Oxaloacetate c. Acetoacetate d. Acetyl CoA What are the starting materials for the processes of ketogenesis and lipogenesis, respectively? a. Acetyl CoA and a fatty acid b. A fatty acid and acetyl CoA c. Acetyl CoA and acetyl CoA d. A fatty acid and a fatty acid Which of the following is an intermediate in the process of lipogenesis? a. Isopentyl pyrophosphate b. Malonyl ACP c. Oxaloacetate d. Acetoacetate

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Protein Metabolism Chapter Outline 26.1 Protein Digestion and Absorption 875 26.2 Amino Acid Utilization 877

26

26.3 Transamination and Oxidative Deamination 878 26.4 The Urea Cycle 883 26.5 Amino Acid Carbon Skeletons 888 26.6 Amino Acid Biosynthesis 891 26.7 Hemoglobin Catabolism 892

CHEMISTRY AT A GLANCE: Interrelationships Among Carbohydrate, Lipid, and Protein Metabolism 895 26.8 Interrelationships Among Metabolic Pathways 896

CHEMICAL CONNECTIONS The Chemical Composition of Urine 889 Arginine, Citrulline, and the Chemical Messenger Nitric Oxide 889

Fish, such as the Atlantic salmon, and other aquatic species process (eliminate) the nitrogen from protein in a manner different from that which occurs in human beings.

F

rom an energy production standpoint, proteins supply only a small portion of the body’s needs. With a normal diet, carbohydrates and fats supply 90% of the body’s energy, and only 10% comes from proteins. However, despite its minor role in energy production, protein metabolism plays an important role in maintaining good health. The amino acids obtained from proteins are needed for both protein synthesis and synthesis of other nitrogen-containing compounds in the cell. In this chapter, we examine protein digestion, the oxidative degradation of amino acids, and amino acid biosynthesis.

26.1 PROTEIN DIGESTION AND ABSORPTION

A very small number of people are unable to synthesize enough stomach acid, and these individuals must ingest capsules of dilute hydrochloric acid with every meal.

Protein digestion begins in the stomach rather than in the mouth because saliva contains no enzymes that affect proteins. Both protein denaturation (Section 20.16) and protein hydrolysis (Section 20.15) occur in the stomach. The partially digested protein (large polypeptides) passes from the stomach into the small intestine, where digestion is completed (Figure 26.1). Proteins are denatured in the stomach by the hydrochloric acid present in gastric juice. The acid gives gastric juice a pH of between 1.5 and 2.0. The enzyme pepsin effects the hydrolysis of about 10% of peptide bonds in proteins, producing a variety of polypeptides. In the small intestine, trypsin, chymotrypsin, and carboxypeptidase in pancreatic juice attack peptide bonds. The pH of pancreatic juice is between 7.0 and 8.0, and it neutralizes the acidity of the material from the stomach. Aminopeptidase, secreted by intestinal mucosal cells, also attacks peptide bonds. Pepsin, trypsin, chymotrypsin,

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Chapter 26 Protein Metabolism

Dietary protein

1. Mouth

Amino acids in bloodstream

4. Intestinal Lining

HCl—denatures protein Pepsin—hydrolyzes peptide bonds

Amino acids

Active transport

Figure 26.1 Summary of protein digestion in the human body.

The passage of polypeptide chains and small proteins across the intestinal wall is uncommon in adults. In infants, however, such transport allows the passage of antibodies (proteins) in colostral milk from a mother to a nursing infant to build up immunologic protection in the infant.

2. Stomach

Saliva—no effect on digestion

Large polypeptides

3. Small Intestine

Trypsin Chymotrypsin Carboxypeptidase Aminopeptidase

Hydrolyze peptide bonds

carboxypeptidase, and aminopeptidase are all examples of proteolytic enzymes (Section 21.8). Enzymes of this type are produced in inactive forms called zymogens that are activated at their site of action (Section 21.9). The net result of protein digestion is the release of the protein’s constituent amino acids. Absorption of these “free” amino acids through the intestinal wall requires active transport with the expenditure of energy (Section 19.10). Different transport systems exist for the various kinds of amino acids. After passing through the intestinal wall, the free amino acids enter the bloodstream, which distributes them throughout the body.

Based on the information in Figure 26.1, determine the location within the human body where each of the following aspects of protein digestion occurs. a. b. c. d.

The enzyme trypsin is active. Large polypeptides are produced. Protein is denatured by HCl. Active transport moves amino acids into the bloodstream.

Solution

a. Trypsin is one of several proteolytic enzymes, found in the small intestine, that hydrolyze peptide bonds. b. Large polypeptides are the product of enzymatic action that occurs in the stomach. c. Protein denaturation, effected by HCl (stomach acid), occurs in the stomach. d. Active transport processes effect the passage of amino acids through the intestinal lining into the bloodstream.

Practice Exercise 26.1 Based on the information in Figure 26.1, determine the location within the human body where each of the following aspects of protein digestion occurs. a. b. c. d.

The enzyme aminopeptidase is active. Peptide bonds are hydrolyzed under the action of pepsin. Individual amino acids are produced. The enzyme carboxypeptidase is active.

Answers: a. Small intestine; b. Stomach; c. Small intestine; d. Small intestine

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26.2 Amino Acid Utilization

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26.2 AMINO ACID UTILIZATION

The rate of protein turnover varies from a few minutes to several hours. Proteins with short turnover rates include many enzymes and regulatory hormones. In a healthy adult, about 2% of the body’s protein is broken down and resynthesized every day.

Higher plants and certain microorganisms are capable of synthesizing all the protein amino acids from carbon dioxide, water, and inorganic salts.

There are approximately 100 grams of free amino acids present in the amino acid pool. Glutamine is the most abundant, followed closely by alamine, glycine, and valine. The essential amino acids constitute approximately 10 grams of the pool.

Amino acids produced from the digestion of proteins enter the amino acid pool of the body. The amino acid pool is the total supply of free amino acids available for use in the human body. Dietary protein is one of three sources that contributes amino acids to the amino acid pool. The other two sources are protein turnover and biosynthesis of amino acids in the liver. Within the human body, proteins are continually being degraded (hydrolyzed) to amino acids and resynthesized. Disease, injury, and “wear and tear” are all causes of degradation. The degradation–resynthesis process is called protein turnover. Protein turnover is the repetitive process in which proteins are degraded and resynthesized within the human body. Biosynthesis of amino acids by the liver also supplies the amino acid pool with amino acids. However, only the nonessential amino acids (Sections 20.2 and 26.6) can be produced in this manner. In a healthy adult, the amount of nitrogen taken into the body each day (dietary proteins) equals the amount of nitrogen excreted from the body. Such a person is said to be in a state of nitrogen balance. Nitrogen balance is the state that results when the amount of nitrogen taken into the human body as protein equals the amount of nitrogen excreted from the body in waste materials. Two types of nitrogen imbalance can occur. When protein degradation exceeds protein synthesis, the amount of nitrogen in the urine exceeds the amount of nitrogen ingested (dietary protein). This condition of negative nitrogen balance accompanies a state of “tissue wasting,” because more tissue proteins are being catabolized than are being replaced by protein synthesis. Protein-poor diets, starvation, and wasting illnesses produce a negative nitrogen balance. A positive nitrogen balance (nitrogen intake exceeds nitrogen output) indicates that the rate of protein anabolism (synthesis) exceeds that of protein catabolism. This state indicates that large amounts of tissue are being synthesized, such as during growth, pregnancy, and convalescence from an emaciating illness. Although the overall nitrogen balance in the body often varies, the relative concentrations of amino acids within the amino acid pool remain essentially constant. No specialized storage forms for amino acids exist in the body, as is the case for glucose (glycogen) and fatty acids (triacylglycerols). Therefore, the body needs a relatively constant source of amino acids to maintain normal metabolism. During negative nitrogen balance, the body must resort to degradation of proteins that were synthesized for other functions. The amino acids from the body’s amino acid pool are used in four different ways. 1. Protein synthesis. It is estimated that about 75% of the free amino acids in a healthy, well-nourished adult go into protein synthesis. Proteins are continually needed to replace old tissue (protein turnover) and also to build new tissue (growth). The subject of protein synthesis was considered in Section 22.11. 2. Synthesis of nonprotein nitrogen-containing compounds. Amino acids are regularly withdrawn from the amino acid pool for the synthesis of nonprotein nitrogen-containing compounds. Such molecules include the purines and pyrimidines of nucleic acids, the heme of hemoglobin, neurotransmitters such as acetylcholine and serotonin, the choline and ethanolamine of phosphoglycerides, and hormones such as epinephrine. 3. Synthesis of nonessential amino acids. When required, the body draws on the amino acid pool for raw materials for the production of nonessential amino acids that are in short supply. The “roadblock” preventing the synthesis of the essential amino acids is not lack of nitrogen but lack of a correct carbon skeleton upon which enzymes can work. In general, the essential amino acids contain carbon chains or aromatic rings not present in other amino acids or the intermediates of carbohydrate or lipid metabolism. Table 26.1 lists the essential amino acids and the nonessential amino acids with the precursors needed to form the latter. 4. Production of energy. Because excess amino acids cannot be stored for later use, the body’s response is to degrade them. The degradation process is complex because each of the 20 standard amino acids has a different degradation pathway.

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TABLE 26.1 Essential and Nonessential Amino Acids

Nutritionally Nonessential Amino Acids

Nutritionally Essential Amino Acids

histidine isoleucine leucine lysine methionine phenylalanine threonine tryptophan valine

Amino Acid

Precursor

alanine arginine asparagine aspartic acid cysteine glutamic acid glutamine glycine proline serine tyrosine

pyruvate glutamate aspartate oxaloacetate serine ␣-ketoglutarate glutamate serine glutamate 3-phosphoglycerate phenylalanine

In all the degradation pathways, the amino nitrogen atom is removed and converted to ammonium ion, which ultimately is excreted from the body as urea. The remaining carbon skeleton is then converted to pyruvate, acetyl CoA, or a citric acid cycle intermediate, depending on its makeup, with the resulting energy production or energy storage. Figure 26.2 shows the various pathways available for the further use of amino acid catabolism products. Subsequent sections of this chapter give further details about these processes.

26.3 TRANSAMINATION AND OXIDATIVE DEAMINATION Degradation of an amino acid has two stages: (1) the removal of the ␣-amino group and (2) the degradation of the remaining carbon skeleton. In this section and the next, we consider what happens to the amino group; in Section 26.5, the fate of the carbon skeleton is considered. The release of an amino group from most amino acids requires a two-step process involving transamination followed by oxidative deamination. The following two procedures will make these processes easier to visualize. Figure 26.2 Possible fates for amino acid degradation products.

Triacylglycerols via fatty acid biosynthesis Glucose via gluconeogenesis Carbon portion ATP via citric acid cycle

Ketone bodies via ketogenesis Amino Acid

Degradation Elimination via urea

Nitrogen portion

Biosynthesis of nonessential amino acids Biosynthesis of nonprotein nitrogen-containing compounds

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26.3 Transamination and Oxidative Deamination

879

1. Draw amino acid structures in the general format ⫹

NH3 R

CH

COO⫺

Remember that the ordering of the four groups attached to the carbon in an amino acid is not critical except in stereochemical considerations (Fischer projection formulas; Section 20.3). 2. Review the structural relationships among six molecules—three pairs of keto/amino acids. In Section 16.5, we noted that the derivatives of three carboxylic acids—propionic (a three-carbon monoacid), succinic (a four-carbon diacid) and glutaric (a fivecarbon diacid)—are particularly important in metabolic reactions. It is the ␣-keto and ␣-amino derivatives of these three acids that are the “key players” in the transamination/oxidative deamination process. Figure 26.3 gives the structural relationships among these compounds.

Transamination A transamination reaction is a biochemical reaction that involves the interchange of the amino group of an a-amino acid with the keto group of an a-keto acid. The general equation for a transamination reaction is ⫹

O NH3 B A ⫺ RO CHOCOO ⫹ R⬘OCO COO⫺ ␣-Amino acid

α-Keto acid

⫹

O NH3 B A ⫺ RO COCOO ⫹ R⬘O CHO COO⫺ New ␣-amino acid

New α-keto acid

Figure 26.3 Key compounds in the transamination/oxidative deamination process include three keto acid/amino acid pairs.

Keto Acid 3-CARBON MONOACID Unsubstituted Acid

CH3

CH2

O CH3

C

COO –

Pyruvate

COO – +

Propionoate

Amino Acid

NH3 CH3

CH

COO –

Alanine

Keto Acid 4-CARBON DIACID Unsubstituted Acid

– OOC

CH2

O – OOC

CH2 C

COO –

Oxaloacetate

CH2 COO –

+

Succinate

Amino Acid

NH3 – OOC

CH2 CH

COO –

Aspartate

Keto Acid

5-CARBON DIACID Unsubstituted Acid

– OOC

CH2

Glutarate

CH2

O –

OOC

CH2

CH2

C

COO –

␣-Ketoglutarate CH2

COO – +

Amino Acid

NH3 – OOC

CH2

Glutamate

CH2

CH

COO –

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The purpose of transamination is to remove amino groups from the various a-amino acids and collect them in a single amino acid, glutamate. Glutamate then acts as the source of amino groups for continued nitrogen metabolism (excretion or biosynthesis).

There are at least 50 aminotransferase enzymes associated with transamination reactions. Most are specific for a-ketoglutarate as the amino group acceptor but are less specific for the amino acid. Glutamate is the amino acid produced from the action of a-ketoglutarate specific aminotransferases. ␣-Amino acid

Reactant

␣-Ketoglutarate

Reactant

Glutamate

Product

Aminotransferase

␣-Keto acid

Product

An important exception to the a-ketoglutarate specificity of aminotransferases is found in muscle cells. Here, many aminotransferases have specificity for the keto acid pyruvate. Alanine is the amino acid produced from the action of such pyruvate specific enzymes. ␣-Amino acid

Reactant

Pyruvate

Reactant

Alanine

Product

Aminotransferase

␣-Keto acid

Product

An example of a transamination reaction where the aminotransferase is a-ketoglutarate specific is COO 

H3N

COO

C OH



COO C

O

C



O

C OH

H3N

H

CH2

H

COO 

CH2

CH2

CH2

COO

COO

␣-Ketoglutarate

Glycine

Ketoacetate

Glutamate

Old amino group carrier

New amino group carrier

An example of a transamination reaction where the aminotransferase is pyruvate specific is COO⫺ ⫹

H3N

COO⫺

C OH ⫹ C H

Glycine

COO⫺ C

O

O

COO⫺ ⫹

H

CH3 Pyruvate

C OH CH3

Ketoacetate

Analine

Old amino group carrier

The concentration of aminotransferases in blood is used to diagnose liver and heart disorders. Liver damage releases the enzyme alanine aminotransferase (ALT) into the blood. Aspartate aminotransferase (AST) is abundant in heart muscle, and increased blood levels of this enzyme indicate heart damage (myocardial infarction).

⫹

H3N

New amino group carrier

The initial effect of transamination reactions is to collect the amino acids from a variety of amino acids into just two amino acids—glutamate (most cells) and alanine (muscle cells). After transport to the liver, alanine is converted to glutamate through a transamination reaction. The net effect of transamination is, thus, the collection of the amino groups from a variety of amino acids into a single compound—the amino acid glutamate. Although the transamination reaction appears to involve the simple transfer of ⫹ an 9⌵H3 group between two molecules, the reaction involves several steps and requires the presence of pyridoxal phosphate, a coenzyme produced from pyridoxine (vitamin B6). HOCH2

CH2OH OH 

N A H Pyridoxine (vitamin B6)

CH3

CHO P OOCH2

OH 

N A H

CH3

Pyridoxal phosphate (coenzyme)

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26.3 Transamination and Oxidative Deamination

Figure 26.4 The role of pyridoxal phosphate in the process of transamination.

O

Step 1 –

P

O

O

–

O

+

H

H3C

COO–

C

+

O

H

O

CH2 NH

H3C

+

COO–

C

+

H3N

Pyridoxal phosphate

Step 2

H

HO CH3 (enzyme-bound)

Pyruvate (product 1)

Pyridoxamine phosphate

O

O –

O

COO C

–

CH2

–

O–

H +

+

H3N

H3N +

NH

H

HO CH3 (enzyme-bound)

COO–

␣ -Ketoglutarate (substrate 2)

+

CH2

C

O

Pyridoxamine phosphate

H

C

P

O–

O

COO–

O

O

CH2

P

+

NH

C

HO CH3 (enzyme-bound)

Alanine (substrate 1)

CH2

H

O

+

C

O–

P

O H3N

Transamination reactions are reversible and can go easily in either direction, depending on the reactant concentrations. This reversibility is the basis for regulation of amino acid concentrations in the body.

O –

H

CH2

+

CH2

O

CH2

C

+

NH

HO CH3 (enzyme-bound)

COO–

Glutamate (product 2)

Pyridoxal phosphate

This coenzyme is an integral part of the transamination process. The amino group of the amino acid is transferred first to the pyridoxal phosphate and then from the pyridoxal phosphate to the a-keto acid. Figure 26.4 shows the role of this coenzyme in the transamination process, where alanine is the amino acid and a-ketoglutarate is the a-keto acid.

Determine the structural formulas for the products in a transamination reaction in which the reactants are aspartate and pyruvate. Solution

Use Figure 26.3 to obtain the structures for the named reactants. Aspartate is an amino acid and pyruvate is a keto acid. COO⫺ ⫹

H3N

C OH

COO⫺

CH2

C

B

COO⫺ Aspartate (amino acid)

O

CH3 Pyruvate (keto acid)

The interchange of functional groups associated with transamination is such that the new keto acid produced will have the same carbon skeleton as the reacting amino acid and the new amino acid produced will have the same carbon skeleton as the reacting keto acid. Same carbon skeleton

Amino acid

⫹

Keto acid

Same carbon skeleton

Keto acid

⫹

Amino acid

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Chapter 26 Protein Metabolism

For aspartate, the reacting amino acid, the functional group change produces the following keto acid, which has the same carbon skeleton as the aspartate. ⫹

COO⫺

C OH

C

CH2

CH2

COO⫺

COO⫺

O

B

H3N

COO⫺

Reacting amino acid

Product keto acid

For pyruvate, the reacting keto acid, the functional group change produces the following amino acid, which has the same carbon skeleton as pyruvate. COO⫺ C

COO⫺ ⫹

O

H3N

B

882

CH3

C OH CH3

Reacting keto acid

Product amino acid

Practice Exercise 26.2 Determine the structural formulas for the products in a transamination reaction in which the reactants are a-ketoglutarate and alanine. Answer:

COO⫺ ⫹

C OH CH2

and

C

O

B

H3N

COO⫺

CH3

CH2 COO⫺

Oxidative Deamination In the second step of amino acid degradation, ammonium ion (NH4⫹) is liberated from the glutamate formed by transamination. This step involves oxidative deamination. An oxidative deamination reaction is a biochemical reaction in which an a-amino acid is converted into an a-keto acid with release of an ammonium ion. Oxidative deamination occurs primarily in liver and kidney mitochondria. Oxidative deamination of glutamate requires the enzyme glutamate dehydrogenase. This enzyme is unusual in that it can function with either NADP⫹ or NAD⫹ as a coenzyme. With NAD⫹ as the coenzyme, the reaction is ⫹

NH3 A ⫺ OOCO CH2 O CH2 OCHO COO⫺ ⫹ NAD⫹ ⫹ H2O Glutamate

Glutamate dehydrogenase

O B

NH4⫹ ⫹ ⫺OOCO CH2 O CH2 O CO COO⫺

⫹ NADH ⫹ H⫹

␣-Ketoglutarate

Note that a-ketoglutarate is a product of this process. It can be reused in the transamination process (first step). The NADH and H⫹ formed can participate in the electron transport chain and oxidative phosphorylation to produce ATP molecules (Sections 23.7 and 23.8).

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26.4 The Urea Cycle

The transamination process previously discussed is not a net deamination (loss of an amino group) process because the reacting a-keto acid becomes aminated as the reacting a-amino acid becomes deaminated.

The sum of the transamination and deamination steps of the degradation of amino acids is a-Amino acid ⫹ NAD⫹ ⫹ H2O 9: a-keto acid ⫹ NH4⫹ ⫹ NADH ⫹ H⫹ The NH4⫹ so produced, a toxic substance if left to accumulate in the body, is then converted to urea in the urea cycle (Section 26.4). Two amino acids, serine and threonine, exhibit different behavior from the other amino acids. They undergo direct deamination by a dehydration–hydration process rather than oxidative deamination. This different behavior results from the presence of a side-chain b-hydroxyl group, a feature unique to these two acids. The direct deamination reaction for serine is COO 

H3N

CH CH2

COO Dehydration



H3N

H2O

COO Isomerization

C CH2



H2N

C CH3

COO Hydrolysis H2O

O



NH4

OH

C CH3

Pyruvate

Serine

Threonine goes through a similar series of steps.

Indicate whether each of the following reaction characteristics is associated with the process of transamination or with the process of oxidative deamination. a. b. c. d.

The enzyme glutamate dehydrogenase is active. The coenzyme pyridoxal phosphate is needed. An amino acid is converted into a keto acid with release of ammonium ion. One of the reactants is an amino acid and one of the products is an amino acid.

Solution

a. Oxidative deamination. The substrate for oxidative deamination is glutamate and the process is an oxidation reaction (removal of H atoms) with NAD⫹ serving as the oxidizing agent. b. Transamination. The coenzyme pyridoxal phosphate, a derivative of vitamin B6, is an intermediate in the amino group transfer process. c. Oxidative deamination. Ammonium ion production is a characteristic of oxidative deamination; no ammonium ion is produced during transamination. d. Transamination. In transamination there are two reactants (an amino acid and a keto acid) and two products (a new amino acid and a new keto acid).

Practice Exercise 26.3 Indicate whether each of the following reaction characteristics is associated with the process of transamination or with the process of oxidative deamination. a. b. c. d.

One of the reactants is a keto acid and one of the products is a keto acid. Enzymes with a specificity toward a-ketoglutarate are often active. NAD⫹ is used as an oxidizing agent. An aminotransferase enzyme is active.

Answers: a. Transamination; b. Transamination; c. Oxidative deamination; d. Transamination

26.4 THE UREA CYCLE From a nitrogen standpoint, the net effect of amino acid degradation is the production of ammonium ion. The accumulation of this ion in the body has potential toxic effects. Consequently, the ammonium ions are converted to urea, a less toxic nitrogen-containing

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Chapter 26 Protein Metabolism

The toxicity of ammonium ion is related to the oxidative deamination reaction by which it is formed, the conversion of glutamate to a-ketoglutarate. This reaction, which is an equilibrium situation, is shifted to the glutamate side by increased ammonium ion levels. This shift decreases a-ketoglutarate levels significantly, which affects the citric acid cycle of which a-ketoglutarate is an intermediate. Cellular ATP production drops, and the lack of ATP causes central nervous system problems.

compound, in the liver by a series of metabolic reactions called the urea cycle. The urea cycle is the series of biochemical reactions in which urea is produced from ammonium ions and carbon dioxide. The urea so produced is then transported in the blood from the liver to the kidneys and eliminated from the body in urine. In the pure state, urea is a white solid with a melting point of 133⬚C. Its structure is O B H2NO CONH2

Urea is very soluble in water (1 g per 1 mL), is odorless and colorless, and has a salty taste. (Urea does not contribute to the odor or color of urine.) With normal metabolism, an adult excretes about 30 g of urea daily in urine, although the exact amount varies with the protein content of the diet. Three amino acids are involved as intermediates in the conversion of ammonium ions to urea through the urea cycle. These acids are arginine, ornithine, and citrulline, the latter two of which are nonstandard amino acids—that is, amino acids not found in protein. Structurally, all three of these amino acids have the same carbon chain. 



NH3 NH2 B A H2NOCONHOCH2 OCH2 OCH2 OCHO COO Arginine is the most nitrogen-rich of the standard amino acids. It contains four nitrogen atoms.

Arginine (standard amino acid) 

NH3 A  H3NOCH2 OCH2 OCH2 OCHO COO Ornithine (nonstandard amino acid) 

O NH3 B A H2NOCONHOCH2 OCH2 OCH2 OCHO COO Citrulline (nonstandard amino acid)

Carbamoyl Phosphate

The functional group attached to the phosphate in carbamoyl phosphate is the simple amide functional group O B O CONH2 The term carbamoyl is the prefix that denotes an amide group. Most often, amide groups are named by using the suffix system, in which case the suffix is amide.

The “fuel” for the urea cycle is the compound carbamoyl phosphate. This fuel is formed from ammonium ion (from oxidative deamination; Section 26.3), carbon dioxide (from the citric acid cycle), water, and two ATP molecules. The formation equation for carbamoyl phosphate is NH4 

CO2  H2O  2ATP

O O B B H2NO COO⬃ P OO  2ADP  Pi  3H A O Carbamoyl phosphate

Note that two ATP molecules are expended in the formation of one carbamoyl phosphate molecule and that carbamoyl phosphate contains a high-energy phosphate bond. The carbamoyl phosphate formation reaction, like the reactions of the citric acid cycle, takes place in the mitochondrial matrix.

Steps of the Urea Cycle Figure 26.5 shows the four-step urea cycle in outline form. Note that the urea cycle occurs partially in the mitochondria and partially in the cytosol and that ornithine and citrulline must be transported across the inner mitochondrial membrane. We will now consider in detail the individual steps of the urea cycle.

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26.4 The Urea Cycle

Figure 26.5 The four-step urea cycle in which carbamoyl phosphate is converted to urea.

Mitochondrial matrix

Carbamoyl phosphate Pi Ornithine transcarbamoylase

Ornithine

Inner mitochondrial membrane

Citrulline

Transfer

1

Transport system

Transport system

Ornithine

Citrulline Hydrolysis

4

Urea

Arginine

Condensation

2

Argininosuccinate synthase

Arginase

H2O

885

3

ATP AMP + PPi

Cleavage Argininosuccinate lyase

Aspartate

Argininosuccinate

Cytosol Fumarate

Step 1: Carbamoyl group transfer. The carbamoyl group of carbamoyl phosphate is

transferred to ornithine to form citrulline in a reaction catalyzed by ornithine transcarbamoylase. 

The standard amino acid lysine and the nonstandard amino acid ornithine, both basic amino acids, have closely related structures. 

NH3 A  H3NO (CH2)4O CHOCOO Lysine 

NH3 A  H3NO (CH2)3O CHOCOO Ornithine

Lysine has one more CH2 group than does ornithine.

H3N A CH2 O O A B B CH2  H2NO C ⬃ OO P OO A A CH2 O A  HO CONH3 A COO Ornithine

Carbamoyl phosphate

O B HONOCONH2 A CH2 A CH2  Pi A CH2 A  NH3 HOCON A COO Citrulline

The breaking of the high-energy phosphate bond in carbamoyl phosphate drives the transfer process. With the carbamoyl transfer, the first of the two nitrogen atoms and the carbon atom needed for the formation of urea have been introduced into the cycle. Step 2: Citrulline–aspartate condensation. Citrulline is transported into the cytosol

where a condensation reaction between citrulline and aspartate (a standard amino acid) produces argininosuccinate. This condensation, catalyzed by argininosuccinate synthase, is driven by the expenditure of ATP.

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Chapter 26 Protein Metabolism

O B HONO CONH2 A CH2 COO A A  CH2  H3NO COH A A CH2 CH2 A  A HO CONH3 COO A COO



AMP  PPi

ATP

H2N COO B A H ONO CONO COH A A A CH2 H CH2 A A CH2 COO A CH2 A  HOC ONH3 A COO

Aspartate

Citrulline

Argininosuccinate

With this reaction, the second of the two nitrogen atoms that will be part of the end-product urea has been introduced into the cycle. One nitrogen atom comes from carbamoyl phosphate, the other from aspartate. However, the original source of both nitrogens is glutamate, the collecting agent for amino acid nitrogen atoms (Section 26.3). The flow of the nitrogen can be shown by these reactions: Glutamate dehydrogenase

Glutamate

aspartate

argininosuccinate

Argininosuccinate cleavage. The enzyme argininosuccinate lyase catalyzes the cleavage of argininosuccinate into arginine, a standard amino acid, and fumarate, a citric acid cycle intermediate. The significance of this will be considered shortly. 



H2N COO A B HONOCONO COH A A A H CH2 CH2 A A COO CH2 A CH2 A  HO CONH3 A COO

H2N B HNOCONH2 A COO H CH2 G D A C B  CH2 A C D G CH2  OOC H A  NH3 HO CON A COO

Argininosuccinate

Step 4:

carbamoyl phosphate

Oxaloacetate

Aminotransferase

Step 3:

NH 4

Arginine

Fumarate

Urea from arginine hydrolysis. Hydrolysis of arginine produces urea and regenerates ornithine, one of the cycle’s starting materials. The enzyme involved is arginase. 

H2NO CPNH2 A NH A CH2 A CH2 A CH2 A  HO CONH3 A COO Arginine



H2O

O B H2NO CONH2

Urea

NH3 A CH2 A  CH2 A CH2 A  HO CONH3 A COO Ornithine

The oxygen atom present in the urea comes from the water involved in the hydrolysis. The ornithine is transported back into the mitrochondria, where it becomes available to participate in the urea cycle again.

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26.4 The Urea Cycle

Carbamoyl phosphate Humans and most terrestrial animals excrete excess nitrogen as urea. Urea is not, however, the only biochemical means for disposing of excess nitrogen. Aquatic species (bacteria and fish) release ammonia directly into the surrounding water. Birds, terrestrial reptiles, and many insects secrete nitrogen as uric acid; it is the familar white solid in bird droppings. The structure of uric acid, a compound with a purine ring system (Section 17.9), is H

A

F

O B

H A N

N A H

N A H

N

O

N1

Citrulline N2

N2

Ornithine

N3 Aspartate

N1

Urea Argininosuccinate N4

N4

Arginine

Figure 26.6 The nitrogen content of the various compounds that participate in the urea cycle.

PO

B

B

887

Uric acid

Figure 26.6 analyzes the urea cycle in terms of the nitrogen content of the various compounds that participate in it. The fuel, the N1 carbamoyl phosphate, condenses with the N2 ornithine to produce the N3 citrulline. Next come two N4 compounds, argininosuccinate and arginine. The N4 arginine undergoes hydrolysis to produce the N2 urea and regenerate the N2 ornithine.

For each of the following urea cycle events identify the urea cycle intermediate that is involved. The urea cycle intermediates are ornithine, citrulline, argininosuccinate, and arginine. a. b. c. d.

Intermediate participates in a condensation reaction. Intermediate is produced at the same time that urea is formed. Intermediate must be transported from the mitochondrial matrix to the cytosol. Intermediate is the product in Step 3 of the urea cycle.

Solution

a. Citrulline. The reaction between citrulline and aspartate in Step 2 of the urea cycle is a condensation reaction. b. Ornithine. In Step 4 of the urea cycle arginine undergoes hydrolysis to produce ornithine and urea. c. Citrulline. Citrulline is formed in the mitochondrial matrix, transported across the inner mitochondrial membrane, and reacts with aspartate in the cytosol. d. Arginine. In Step 3 of the urea cycle, in a cleavage reaction, the large molecule argininosuccinate is split into two pieces—the smaller arginine and fumarate molecules.

Practice Exercise 26.4 For each of the following urea cycle events identify the urea cycle intermediate that is involved. The urea cycle intermediates are ornithine, citrulline, argininosuccinate, and arginine. a. b. c. d.

Intermediate reacts with carbamoyl phosphate. Intermediate must be transported from the cytosol to the mitochondrial matrix. Intermediate is a reactant in a hydrolysis reaction. Intermediate is the reactant in Step 2 of the urea cycle.

Answers: a. Ornithine; b. Ornithine; c. Arginine; d. Citrulline

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␣-Ketoglutarate

Figure 26.7 Fumarate from the urea cycle enters the citric acid cycle, and aspartate produced from oxaloacetate of the citric acid cycle enters the urea cycle.

Aspartate

Carbamoyl phosphate

Ornithine

Glutamate

Citrulline Oxaloacetate

Urea Cycle

Argininosuccinate Malate

Citric Acid Cycle

Urea Arginine

Fumarate

Urea Cycle Net Reaction Sulfur-containing amino acids (cysteine and methionine) contain both sulfur and nitrogen. The nitrogen-containing group is lost through transamination and oxidative deamination and processed to urea. The sulfur-containing group is processed to sulfur dioxide (SO2), which is then oxidized to sulfate (SO42⫺). The SO42⫺ ion, the negative ion from sulfuric acid, is eliminated in urine.

The net reaction for urea formation, in which all of the urea cycle intermediates cancel out of the equation, is NH 4  CO2  3ATP  2H2O  aspartate ¡ urea  2ADP  AMP  PPi  2Pi  fumarate The equivalent of a total of four ATP molecules is expended in the production of one urea molecule. Two ATP molecules are consumed in the production of carbamoyl phosphate, and the equivalent of two ATP molecules is consumed in Step 2 of the urea cycle, where an ATP is hydrolyzed to AMP and PPi and the PPi is then further hydrolyzed to two Pi.

Linkage Between the Urea and Citric Acid Cycles The net equation for urea formation shows fumarate, a citric acid cycle intermediate, as a product. This fumarate enters the citric acid cycle, where it is converted to malate and then to oxaloacetate, which can then be converted to aspartate through transamination. The aspartate then re-enters the urea cycle at Step 2 (see Figure 26.7). Besides undergoing transamination, the oxaloacetate produced from fumarate of the urea cycle can be (1) converted to glucose via gluconeogenesis, (2) condensed with acetyl CoA to form citrate, or (3) converted to pyruvate.

26.5 AMINO ACID CARBON SKELETONS

The 20 standard amino acids are degraded by 20 different pathways that converge to produce just 7 products (metabolic products).

The removal of the amino group of an amino acid by transamination/oxidative deamination (Section 26.3) produces an a-keto acid that contains the carbon skeleton from the amino acid. Each of the 20 amino acid carbon skeletons undergoes a different degradation process. For alanine and serine, the degradation requires a single step. For most carbon arrangements, however, multistep reaction sequences are required. We will not consider the details of these various degradation procedures in this text. It is important, however, to consider the products of these 20 degradation sequences. There are only seven, and each is a compound that we have previously encountered in our discussions of metabolism. The seven degradation products are pyruvate, acetyl CoA, acetoacetyl CoA, a-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate. The last four products are intermediates in the

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HEMICAL

onnections

The Chemical Composition of Urine

Urine is a dilute aqueous solution containing many solutes whose concentrations are dependent on the diet and state of health of the individual. On average, about 4 g of solutes are present in a 100-g urine sample; thus urine is an approximately 4%-by-mass aqueous solution of materials eliminated from the body. The solutes present in urine are of two general types: organic compounds and inorganic ions. Generally, the organic compounds are more abundant because of the dominance of urea, as shown in the following composition data. Major Constituents of Urine (for a 1400-mL specimen obtained over a 24-hour period) Organic Constituents

Inorganic Constituents

urea creatinine amino acids uric acid

chloride (Cl⫺) sodium (Na⫹) potassium (K⫹) sulfate (SO42⫺) dihydrogen phosphate (H2PO4⫺) ammonium (NH4⫹) calcium (Ca2⫹) magnesium (Mg2⫹)

25.0 g 1.5 g 0.8 g 0.7 g

c

6.3 g 3.0 g 1.7 g 1.4 g 1.2 g 0.8 g 0.2 g 0.2 g

Urea, the solute present in the greatest quantity in urine, is odorless and colorless in solution (Section 26.4). (The pale yellow color of urine is due to small amounts of urobilin and related compounds, as discussed in Section 26.7.) Urea is the principal nitrogen-containing end product of protein metabolism. Creatinine, the second most abundant organic product in urine, is produced from the amino acids arginine, methionine, and glycine. Uric acid is a product of the metabolism of purines from nucleic acids. The most abundant inorganic constituent of urine is chloride ion. Its primary source is dietary table salt (NaCl). Correspondingly, the second most abundant ion present is sodium ion, the positive ion in table salt. The sulfate ion present in urine comes primarily from the metabolism of sulfur-containing amino acids. Ammonium ions come primarily from the hydrolysis of urea. Urine is normally slightly acidic, having an average pH value of 6.6. However, the pH range is wide—from 4.5 to 8.0. Fruits and vegetables in the diet tend to raise urine pH, and high-protein foods tend to lower urine pH. A normal adult excretes 1000–1500 mL of urine daily. Actual urine volume depends on liquid intake and weather. During hot weather, urine volume decreases as a result of increased water loss through perspiration.

HEMICAL

onnections

Arginine, Citrulline, and the Chemical Messenger Nitric Oxide

A somewhat startling biochemical discovery made during the early 1990s was the existence within the human body of a gaseous chemical messenger, the simple diatomic molecule nitric oxide (NO). Its production involves two of the amino acid intermediates of the urea cycle—arginine and citrulline. Arginine reacts with oxygen to produce citrulline and NO. The reaction requires NADPH and the enzyme nitric oxide synthase (NOS). NH2 A  CPNH2 A NH O2  A (CH2)3 A  HCONH3 A COO Arginine

Nitric oxide synthase NADPH

NADP

NH2 A C PO A NH A  NO (CH2)3 A  HCONH3 A COO Citrulline

Even though this reaction involves urea cycle intermediates, it is completely independent of the urea cycle. Nitric oxide affects many kinds of cells and has particularly striking effects in the following areas:

1. NO helps maintain blood pressure by dilating blood vessels. 2. NO is a chemical messenger in the central nervous system. 3. NO is involved in the immune system’s response to invasion by foreign organisms or materials. 4. NO is found in the brain and may be a major biochemical component of long-term memory. In humans, nitric oxide is the first known biochemical messenger compound that is a gas. It can easily pass through cell membranes by diffusion. No specific receptor or transport system is needed. Because of its extreme reactivity, NO exists for less than 10 seconds before undergoing reaction. This high reactivity prevents it from getting more than 1 millimeter from its site of synthesis. The action of nitroglycerin, when it is used as a heart medication (for angina pectoris), is now known to be related to NO. Nitric oxide is the active metabolite from nitroglycerin. Before the discovery of nitric oxide’s role as a biochemical messenger, this gas was thought of mainly as a noxious atmospheric gas found in cigarette smoke and smog, as a destroyer of ozone, and as a precursor of acid rain. The contrast between nitric oxide’s role in environmental pollution and its function in the human body as a chemical messenger is indeed startling.

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Only amino acids that can replenish, either directly or indirectly, oxaloacetate supplies, are glucogenic, that is, can be used to produce glucose through gluconeogenesis.

citric acid cycle. Figure 26.8 relates these seven degradation products to the amino acids from which they are obtained. Some amino acids appear in more than one box in Figure 26.8. This means either that there is more than one pathway for degradation or that some of the carbon atoms of the skeleton emerge as one product and others as another product. Amino acids that are degraded to citric acid cycle intermediates can serve as glucose precursors and are called glucogenic. A glucogenic amino acid is an amino acid that has a carbon-containing degradation product that can be used to produce glucose via gluconeogenesis. Amino acids that are degraded to acetyl CoA or acetoacetyl CoA can contribute to the formation of fatty acids or ketone bodies and are called ketogenic. A ketogenic amino acid is an amino acid that has a carbon-containing degradation product that can be used to produce ketone bodies. Even though acetyl CoA can enter the citric acid cycle, there can be no net production of glucose from it. Acetyl groups are C2 species, and such species only maintain the carbon count in the cycle because two CO2 molecules exit the cycle (Section 23.6). Thus amino acids that are degraded to acetyl CoA (or acetoacetyl CoA) are not glucogenic. Amino acids that are degraded to pyruvate can be either glucogenic or ketogenic. Pyruvate can be metabolized to either oxaloacetate (glucogenic) or acetyl CoA (ketogenic). Only two amino acids are purely ketogenic: leucine and lysine. Nine amino acids are both glucogenic and ketogenic: those degraded to pyruvate (see Figure 26.8), as well as tyrosine, phenylalanine, and isoleucine (which have two degradation products). The remaining nine amino acids are purely glucogenic. Our discussion of glucogenicity and ketogenicity for amino acids points out that ATP production (common metabolic pathway) is not the only fate for amino acid degradation products. They can also be converted to glucose, ketone bodies, or fatty acids (via acetyl CoA).

Alanine Glycine Cysteine Serine Threonine Tryptophan*

Isoleucine* Leucine* Tryptophan*

Leucine* Lysine Phenylalanine* Tyrosine* Tryptophan*

Acetyl CoA

Acetoacetyl CoA

Pyruvate Glucose

Asparagine Aspartate*

Oxaloacetate

Ketone bodies Tyrosine* Phenylalanine* Aspartate*

Fumarate

Citric Acid Cycle ␣-Ketoglutarate

Figure 26.8 Fates of the carbon skeletons of amino acids. Glucogenic amino acids are shaded blue, and ketogenic amino acids are shaded green. Some amino acids (marked with an asterisk) have more than one degradation pathway, and thus are present more than once in the diagram.

Succinyl CoA

Isoleucine* Methionine Valine

Glutamate Glutamine Histidine Proline Arginine

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26.6 AMINO ACID BIOSYNTHESIS

There is considerable variation in biosynthetic pathways for amino acids among different species. By contrast, the basic pathways of carbohydrate and lipid metabolism are almost universal.

The classification of amino acids as essential or nonessential for humans (Section 20.2) roughly parallels the number of steps in their biosynthetic pathways and the energy required for their synthesis. The nonessential amino acids can be made in 1–3 steps. The essential ones have biosynthetic pathways that require 7–10 steps, judging on the basis of observations of their synthesis in microorganisms. Most bacteria and plants can synthesize all the amino acids by pathways not present in humans. Plants, consumed as food, are the major source of the essential amino acids in humans and animals. The starting materials for the biosynthesis of the 11 nonessential amino acids are the glycolysis intermediates 3-phosphoglycerate and pyruvate and the citric acid cycle intermediates oxaloacetate and a-ketoglutarate (see Figure 26.9). Three of the nonessential amino acids—alanine, aspartate, and glutamate—are biosynthesized by transamination (Section 26.3) of the appropriate a-keto acid starting material. O B CH3 O CO COO



NH3 A CH3 O CHO COO

Transamination

Alanine

Pyruvate

O B  OOCO CH2 O COCOO



NH3 A  OOCOCH2 O CHO COO

Transamination

Oxaloacetate

O B  OOCO CH2 O CH2 O COCOO

Aspartate 

NH3 A  OOCOCH2 O CH2 O CHO COO

Transamination

␣-Ketoglutarate

Glutamate

Cysteine

Glycolysis Intermediates

3-Phosphoglycerate

Serine Glycine

Pyruvate

Oxaloacetate

Alanine

Aspartate

Citric Acid Cycle Intermediates

Asparagine Arginine

-Ketoglutarate

Glutamate

Proline Glutamine

Essential Amino Acid

Phenylalanine

Tyrosine

Figure 26.9 A summary of the starting materials for the biosynthesis of the 11 nonessential amino acids.

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PKU is characterized by elevated blood levels of phenylalanine and phenylpyruvate. The physical consequence of PKU is damage to developing brain cells. In children up to six years old, PKU leads to retarded mental development. The major defense against PKU is mandatory screening of newborns to identify the one in every 20,000 who is afflicted and then restricting those children’s dietary phenylalanine intake to that needed for protein synthesis until they are six years old. After that age, brain cells are not so susceptible to the toxic effect of phenylpyruvate.

The nonessential amino acid tyrosine is obtained from the essential amino acid phenylalanine in a one-step oxidation that involves molecular O2, NADPH, and the enzyme phenylalanine hydroxylase. Lack of this enzyme causes the metabolic disease phenylketonuria (PKU).

26.7 HEMOGLOBIN CATABOLISM Red blood cells are highly specialized cells whose primary function is to deliver oxygen to, and remove carbon dioxide from, body tissues. Mature red blood cells have no nucleus or DNA. Instead, they are filled with the red pigment hemoglobin. Red blood cell formation occurs in the bone marrow, and approximately 200 billion new red blood cells are formed daily. The life span of a red blood cell is about 4 months. The oxygen-carrying ability of red blood cells is due to the protein hemoglobin present in such cells (see Figure 26.10). Hemoglobin is a conjugated protein (Section 20.8); the protein portion is called globin, and the prosthetic group (nonprotein portion) is heme. Heme contains four pyrrole groups (Section 17.9) joined together with an iron atom in the center.

Figure 26.10 A molecular model of the protein hemoglobin.

N A H Pyrrole

CHPCH2

H3C H3C N OOC

The tetrapyrrole heme ring is the only component of hemoglobin that is not reused by the body.

CH2 OOC

CH2 CH2

N A Fe2 N A N

CH3

CHP CH2

CH3

CH2 Heme

It is the iron atom in heme that interacts with O2, forming a reversible complex with it. This complexation increases the amount of O2 that the blood can carrry by a factor of 80 over that which simply “dissolves” in the blood. Old red blood cells are broken down in the spleen (primary site) and liver (secondary site). Part of this process is degradation of hemoglobin. The globin protein is hydrolyzed to amino acids, which become part of the amino acid pool (Section 26.2). The iron atom of heme becomes part of ferritin, an iron-storage protein, which saves the iron for use in the biosynthesis of new hemoglobin molecules. The tetrapyrrole carbon arrangement of

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26.7 Hemoglobin Catabolism

CHPCH2

H3C A

H3C N

D OOC

CH2

CH2

This carbon is removed.

CH3

N A Fe2 N A N

893

Fe3

H2O

 2O2

B

NADPH

CHPCH2

NADP

C OOC

CH2

CH2

CH3 Heme

CHP CH2

H3C H3C N OOC

CH2

CH2

O

CH3  CO

N

H A N

CH2

OOC

O

N

CHP CH2 CH3

CH2 Biliverdin

The level of carbon monoxide produced in the first step of hemoglobin degradation is sufficient to complex 1% of the oxygen-binding sites of the blood’s hemoglobin.

heme is degraded to bile pigments that are eliminated in feces and to a lesser extent in urine. Degradation of heme begins with a ring-opening reaction in which a single carbon atom is removed. The product is called biliverdin. This reaction has several important characteristics. (1) Molecular oxygen, O2, is required as a reactant. (2) Ring opening releases the iron atom to be incorporated into ferritin. (3) The product containing the excised carbon atom is carbon monoxide (a substance toxic to the human body). The carbon monoxide so produced reacts with functioning hemoglobin, forming a CO–hemoglobin complex; this decreases the oxygen-carrying ability of the blood. CO–hemoglobin complexes are very stable; CO release to the lungs is a slow process. An alternative rendering of the structure of biliverdin is

M

V

M

N A H

P

C

B

O

P

C

N

M

M A

D

C

N A H

V

C

N A H

O

Biliverdin M  OCH3 (methyl) V  OCHPCH2 (vinyl) P  OCH2OCH2OCOO (propionate)

This structure employs a notation, common in heme chemistry, in which letters are used to denote attachments to the pyrrole rings; such notation easily distinguishes the attachments. The structure’s linear arrangement of pyrrole rings also saves space compared to the heme-like representation of the rings. However, the linear structure incorrectly implies that the arrangement of the pyrrole rings that results from the ring opening is linear (straight-line); rather, the pyrrole rings actually have a hemi-like arrangement. In the second step of heme degradation, biliverdin is converted to bilirubin. This change involves reduction of the central methylene bridge of biliverdin.

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Chapter 26 Protein Metabolism

Biliverdin

F

In 2002 it was discovered that bilirubin has antioxidant properties. It protects against peroxyl radicals (Section 23.11) by being oxidized back to biliverdin. Its antioxidant properties are significantly better than those of glutathione (Section 20.7), the molecule believed for 80 years to be the most important cellular antioxidant. Bilirubin is found only in low concentrations in cells but in higher concentrations in blood. This new research suggests that bilirubin is probably the major antioxidant protector for cell membranes, while glutathione protects components inside cells.

NADPH ⫹ H⫹ NADP⫹

M

V

O

N A H

M

P

N A H

C

M

P

M

N A H

C Bilirubin

The change from heme to biliverdin to bilirubin usually occurs in the spleen. The bilirubin is then transported by serum albumin to the liver, where it is rendered more water-soluble by the attachment of sugar residues to its propionate side chains (P side chains). The solubilizing sugar is glucuronate (glucose with a —COO⫺ group on C-6 instead of a —CH2OH group). COO⫺

O

O

OH

OH

HO

O OH

1. Latin virdis means “green”; biliverdin ⫽ “green bile.” 2. Latin rubin means “red”; bilirubin ⫽ “red bile.” 3. Latin urina means “urine”; urobilin ⫽ “urine bile.” 4. Latin sterco means “dung”; stercobilin ⫽ “dung bile.”

O

N A H

C

COO⫺

The first part of the names biliverdin and bilirubin and the last part of the names stercobilin and urobilin all come from the Latin bilis, which means “bile.” As for the other parts of the names:

V

OH

O OH

Bilirubin

Bilirubin diglucuronide

The solubilized bilirubin is excreted from the liver in bile, which flows into the small intestine. Here the bilirubin diglucuronide is changed, in a multistep process, to either stercobilin for excretion in feces or urobilin for excretion in urine. Both stercobilin and urobilin still have tetrapyrrole structures (Figure 26.11). Intestinal bacteria are primarily responsible for the changes that produce stercobilin and urobilin.

M

O

V

N

M

C

P

N

H

P

C

H

M

N

M

V

N

C

H

O

H

Bilirubin

M

O

E

N H

Figure 26.11 Stercobilin and urobilin have structures closely resembling that of bilirubin. Changes include reduction of vinyl (V) groups to ethyl (E) groups and reduction of OCH2O bridges.

M

C

P

N

P

C

M

N

M

C

E

N H

H

M

O

O

E

N H

M

C

P

N

P

C

M

N

H

M

C

E

N H

Urobilin

Stercobilin

Urine

Feces

O

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Bile Pigments The word jaundice comes from the French jaune, which means “yellow.”

A mild form of jaundice is common among premature infants because of underdeveloped liver function. Treatment involves the use of white or ultraviolet light, which breaks the bilirubin down to simpler compounds that are more easily excreted.

The tetrapyrrole degradation products obtained from heme are known as bile pigments because they are secreted with the bile (Section 25.1), and most of them are highly colored. A bile pigment is a colored tetrapyrrole degradation product present in bile. Biliverdin and bilirubin are, respectively, green and reddish orange in color. Stercobilin has a brownish hue and is the compound that gives feces their characteristic color. Urobilin is the pigment that gives urine its characteristic yellow color. Normally, the body excretes 1–2 mg of bile pigments in urine daily and 250–350 mg of bile pigments in feces daily. When the body is functioning properly, the degradation of heme in the spleen to bilirubin and the removal of bilirubin from the blood by the liver balance each other. Jaundice is the condition that occurs when this balance is upset such that bilirubin concentrations in the blood become higher than normal. The skin and the white of the

Interrelationships Among Carbohydrate, Lipid, and Protein Metabolism Dietary lipids

Fatty acids

LIPOGENESIS

Glycerol

GLYCOLYSIS

Dietary carbohydrates

Dietary proteins

Glucose

Amino acids

Nonprotein nitrogen compounds

TRANSAMINATION/ DEAMINATION

Nonessential amino acids

GLUCONEOGENESIS

Tissue proteins

Pyruvate β-OXIDATION PATHWAY

Acetoacetyl CoA -Keto acids

Acetyl CoA

CITRIC ACID CYCLE

+

NH4+

Oxaloacetate UREA CYCLE

Aspartate Fumarate

ELECTRON TRANSPORT CHAIN

ATP

Urea

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Chapter 26 Protein Metabolism

eyes acquire a yellowish tint because of the excess bilirubin in the blood. Jaundice can occur as a result of liver diseases, such as infectious hepatitis and cirrhosis, that decrease the liver’s ability to process bilirubin; from spleen malfunction, in which heme is degraded more rapidly than it can be absorbed by the liver; and from gallbladder malfunction, usually from an obstruction of the bile duct. The local coloration associated with a deep bruise is also related to the pigmentation associated with heme, biliverdin, and bilirubin. The changing color of the bruise as it heals reflects the dominant degradation product present at the time as the tissue repairs itself.

26.8 INTERRELATIONSHIPS AMONG METABOLIC PATHWAYS

Figure 26.12 The human body’s response to feasting, to fasting, and to starvation.

In this chapter and the previous two chapters, we have considered metabolic pathways of carbohydrates, lipids, and proteins. These pathways are not independent of each other but rather are integrally linked, as shown in the Chemistry at a Glance feature on page 895.

Component to be broken down

End products of digestion or catabolism

Fate

Feasting (overeating) Ingestion of food in excess of energy needs causes the body to store a limited amount as glycogen and the rest as fat.

Fasting (no food ingestion) When no food is ingested, the body uses its stored glycogen and fat for energy.

Dietary carbohydrate

Glucose

Stored as glycogen in liver and muscle

Dietary fat

Fatty acid

Stored as body fat

Dietary protein

Amino acids

Nitrogen lost in urine (urea)

Glycogen in liver and muscle

Glucose

Brain energy

Body fat

Fatty acids

Energy

Starvation (continued fasting beyond glycogen depletion) When glycogen stores are depleted, body protein is broken down to amino acids, which are used to synthesize glucose. The glucose serves as an energy source for the brain and nervous system. Also, in the liver, fats are converted to ketone bodies, which are another energy source for the brain.

Nitrogen lost in urine (urea)

Body protein

Amino acids

Glucose

Body fat

Fatty acids

Ketone bodies

Brain energy

Energy

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Exercises and Problems

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The numerous connections among pathways mean that a change in one pathway can affect many other pathways. A good illustration of the interrelationships among pathways emerges from comparing the processes of eating (feasting), not eating for a short period (fasting), and not eating for a prolonged period (starvation). Figure 26.12 shows how the body responds to each of these situations.

c

O N C E P TS TO R E M E M B E R

Protein digestion and absorption. Digestion of proteins involves

Urea cycle. The urea cycle is the metabolic pathway that converts

the hydrolysis of the peptide bonds that link amino acids to each other. This process begins in the stomach and is completed in the small intestine. The amino acids released by digestion are absorbed through the intestinal wall into the bloodstream (Section 26.1). Amino acid pool. The amino acid pool within cells consists of varying amounts of each of the 20 standard amino acids found in proteins (Section 26.2). Amino acid utilization. Amino acids from the amino acid pool are used for protein synthesis, synthesis of nonprotein nitrogen compounds, synthesis of nonessential amino acids, and energy production (Section 26.2). Transamination. A transamination reaction is an enzyme-catalyzed transfer of an amino group from an a-amino acid to an a-keto acid. Transamination is a step in obtaining energy from amino acids (Section 26.3). Oxidative deamination. An oxidative deamination reaction is a reaction in which an a-amino acid is converted into an a-keto acid, accompanied by the release of a free ammonium ion. Oxidative deamination is a step in obtaining energy from amino acids (Section 26.3).

ammonium ions into urea. This cycle processes the ammonium ions in the form of carbamoyl phosphate, a compound formed from CO2, NH4⫹, ATP, and H2O (Section 26.4). Amino acid carbon skeletons. Amino acid carbon skeletons (keto acids) are classified as glucogenic or ketogenic on the basis of their catabolic pathways. Glucogenic amino acids are degraded to intermediates of the citric acid cycle and can be used for glucose synthesis. Ketogenic amino acids are degraded into acetoacetyl CoA or acetyl CoA and can be used to make ketone bodies (Section 26.5). Amino acid biosynthesis. Amino acid biosynthesis is the process in which the body synthesizes amino acids from intermediates of the glycolysis pathway and the citric acid cycle. Eleven amino acids can be synthesized by the body. The other nine amino acids, called essential amino acids, must be obtained from the diet (Section 26.6). Hemoglobin catabolism. Hemoglobin from red blood cells undergoes a stepwise degradation to biliverdin, to bilirubin, and then to bile pigments that are excreted from the body (Section 26.7).

k

EY R E A C T I O N S A N D E Q U AT I O N S

1. Digestion of protein (Section 26.1) Pancreatic enzymes

Protein 888888888888n amino acids and HCl

2. Transamination (Section 26.3) ⫹

NH3 O A B ⫺ R1 OCHOCOO ⫹ R2 OC OCOO⫺ ⫹ O NH3 B A R1O COCOO⫺ ⫹ R2 OCHOCOO⫺

3. Oxidative deamination (Section 26.3)

NH3⫹ A R OCHOCOO⫺ ⫹ NAD⫹ ⫹ H2O O B RO C OCOO⫺ ⫹ NH4⫹ ⫹ NADH ⫹ H⫹ 4. Formation of urea (Section 26.4) NH 4⫹ ⫹ CO2 ⫹ 3ATP ⫹ 2H2O ⫹ aspartate ¡ urea ⫹ fumarate ⫹ 2ADP ⫹ AMP ⫹ PPi ⫹ 2Pi

EXERCISES an d PR O BL EMS The members of each pair of problems in this section test similar material. Protein Digestion and Absorption (Section 26.1) 26.1 The first step in protein digestion is denaturation. Where does

denaturation occur in the body, and what is the denaturant? 26.2 What is the first digestive enzyme that protein encounters, and where does this encounter take place?

26.3 What is the relationship between pepsinogen and pepsin? 26.4 What is the relationship between trypsinogen and trypsin? 26.5 Contrast gastric juice and pancreatic juice in terms of pH. 26.6 Contrast gastric juice and pancreatic juice in terms of enzymes

present.

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Chapter 26 Protein Metabolism

26.7 Absorption of amino acids through the intestinal wall requires a

transport system. Explain. 26.8 The passage of small polypeptides through the intestinal wall is particularly important in infants. Explain. Amino Acid Utilization (Section 26.2)

26.28 The net effect of transamination is to collect the amino groups

26.29 26.30

26.9 What is the amino acid pool? 26.10 What are the three major sources of amino acids for the amino

acid pool?

26.11 What is protein turnover? 26.12 The protein turnover rate is not the same for all proteins.

Explain.

26.13 What is the difference between a positive nitrogen balance and

a negative nitrogen balance?

26.31 26.32 26.33 26.34 26.35

26.14 What happens to the nitrogen balance during a period of

fasting?

26.15 What happens to the nitrogen balance when the diet is lacking

in one of the essential amino acids? 26.16 What happens to the nitrogen balance of a pregnant woman?

26.36

26.17 What four types of processes draw amino acids out of the

amino acid pool?

26.18 What percent of amino acid utilization from the amino acid

pool is for protein synthesis?

26.19 Classify each of the following amino acids as essential or

nonessential. a. Lysine b. Arginine c. Serine d. Tryptophan 26.20 Classify each of the following amino acids as essential or nonessential. a. Proline b. Asparagine c. Glutamic acid d. Tyrosine 26.21 Which of the amino acids in Problem 26.19 can be biosynthesized

26.37

from a variety of a-amino acids into the compound glutamate. Explain. What is the function of pyridoxal phosphate in transamination processes? Which one of the B vitamins is important in the process of transamination? Describe the process of oxidative deamination. What coenzyme is required for an oxidative deamination reaction? How does oxidative deamination differ from transamination? What do the processes of oxidative deamination and transamination have in common? Draw the structure of the a-keto acid produced from the oxidative deamination of each of the following amino acids. a. Glutamate b. Cysteine c. Alanine d. Phenylalanine Draw the structure of the a-keto acid produced from the oxidative deamination of each of the following amino acids. a. Glycine b. Leucine c. Aspartate d. Tyrosine The following a-keto acid can be used as a substitute for a particular essential amino acid in the diet. Explain how this is possible, and draw the structure of the essential amino acid.

O B CH3O CHOCH2OCO COO A CH3 26.38 The following a-keto acid can be used as a substitute for a

particular essential amino acid in the diet. Explain how this is possible, and draw the structure of the essential amino acid.

in the human body?

O B CH3O CH2O CHOCO COO A CH3

26.22 Which of the amino acids in Problem 26.20 can be biosynthesized

in the human body?

Transamination and Oxidative Deamination (Section 26.3) 26.23 In general terms, what are the two reactants in a transamination reaction? 26.24 In general terms, what are the two products in a transamination reaction? 26.25 Write structural equations for the transamination reactions that

involve the following pairs of reactants. a. Threonine and pyruvate b. Alanine and oxaloacetate c. Glycine and a-ketoglutarate d. Threonine and a-ketoglutarate 26.26 Write structural equations for the transamination reactions that involve the following pairs of reactants. a. Threonine and oxaloacetate b. Glycine and pyruvate c. Alanine and oxaloacetate d. Isoleucine and a-ketoglutarate 26.27 What are the two a-keto acids that are most often reactants in

transamination reactions?

26.39 Give the name of the compound produced from each reactant

or the reactant needed to produce each product using transamination. a. Oxaloacetate ¡ ? b. ? ¡ a-ketoglutarate c. Alanine ¡ ? d. ? ¡ glutamate 26.40 Give the name of the compound produced from each reactant or the reactant needed to produce each product using transamination. a. Pyruvate ¡ ? b. ? ¡ oxaloacetate c. Aspartate ¡ ? d. ? ¡ alanine

The Urea Cycle (Section 26.4) 26.41 Draw the chemical structure of urea. 26.42 What are some of the physical characteristics of urea? 26.43 In what chemical form do ammonium ions enter the urea

cycle?

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Exercises and Problems

26.44 What are the chemical reactants for the formation of carbamoyl

phosphate?

26.45 What is a carbamoyl group? 26.46 Draw the structure of the molecule carbamoyl phosphate. 26.47 How do the structures of the three amino acids involved as

intermediates in the urea cycle differ from each other?

26.48 Three amino acids are involved as intermediates in the urea

cycle. Name them and classify them as standard or nonstandard amino acids.

26.49 Name the compound that enters the urea cycle by combining

with a. ornithine. b. citrulline. 26.50 Identify the first reaction of the urea cycle that occurs in the a. mitochondrial matrix. b. cytosol. 26.51 What substance is the “fuel” for the urea cycle?

26.52 If the urea cycle were named in the same way as the citric acid

cycle, what would the cycle’s name be?

26.53 Characterize each of the following “urea cycle compounds” in

terms of its nitrogen content (N1, N2, N3, or N4). a. Ornithine b. Citrulline c. Aspartate d. Argininosuccinate 26.54 Characterize each of the following “urea cycle compounds” in terms of its nitrogen content (N1, N2, N3, or N4). a. Carbamoyl phosphate b. Ammonium ion c. Aspartate d. Urea 26.55 In each of the following pairs of compounds associated with

the urea cycle, specify which one is encountered first in the cycle. a. Citrulline and arginine b. Ornithine and aspartate c. Argininosuccinate and fumarate d. Carbamoyl phosphate and citrulline

26.56 In each of the following pairs of compounds associated with

the urea cycle, specify which one is encountered first in the cycle. a. Carbamoyl phosphate and fumarate b. Argininosuccinate and arginine c. Ornithine and aspartate d. Citrulline and ATP

899

26.63 With the help of Figure 26.8, write the name of the compound

(or compounds) to which each of the following amino acid carbon skeletons is metabolized. a. Leucine b. Isoleucine c. Aspartate d. Arginine

26.64 With the help of Figure 26.8, write the name of the compound

(or compounds) to which each of the following amino acid carbon skeletons is metabolized. a. Serine b. Tyrosine c. Tryptophan d. Histidine

26.65 What degradation characteristics do all purely glucogenic

amino acids share?

26.66 What degradation characteristics do all purely ketogenic

amino acids share?

Amino Acid Biosynthesis (Section 26.6) 26.67 What compound is a major source of amino groups in amino

acid biosynthesis?

26.68 How does transamination play a role in both catabolism and

anabolism of amino acids?

26.69 What are the five starting materials for the biosynthesis of the

11 nonessential amino acids?

26.70 What is a major difference between the biosynthetic pathways

for the essential and the nonessential amino acids?

Hemoglobin Catabolism (Section 26.7) 26.71 What happens to the globin produced from the breakdown of

hemoglobin?

26.72 What happens to the iron (Fe2⫹) produced from the breakdown

of hemoglobin?

26.73 What are the structural differences between heme and

biliverdin?

26.74 What are the structural differences between biliverdin and

bilirubin?

26.75 Arrange the following substances in the order in which they

are encountered during the catabolism of heme: bilirubin, urobilin, biliverdin, and bilirubin diglucuronide.

26.76 Carbon monoxide is a by-product of the degradation of heme.

At what point in the degradation process is it formed, and what happens to it once it is formed?

26.77 Which bile pigment is responsible for the yellow color of urine?

26.57 How much energy, in terms of ATP, is expended in the synthesis

26.78 Which bile pigment is responsible for the brownish-red color of

26.58 What are the sources of the carbon atom and the two nitrogen

26.79 What chemical condition is responsible for jaundice?

of a molecule of urea? atoms in urea?

26.59 What is the fate of the fumarate formed in the urea cycle? 26.60 Explain how the urea cycle is linked to the citric acid cycle.

Amino Acid Carbon Skeletons (Section 26.5) 26.61 What are the four possible degradation products of the carbon skeletons of amino acids that are citric acid cycle intermediates? 26.62 What are the three possible degradation products of the carbon skeletons of amino acids that are not citric acid cycle intermediates?

feces?

26.80 What physical conditions cause jaundice?

Interrelationships of Metabolic Pathways (Section 26.8) 26.81 Briefly explain how the carbon atoms from amino acids can end up in ketone bodies. 26.82 Briefly explain how the carbon atoms from amino acids can end

up in glucose.

26.83 How are the amino acids from protein “processed” when they

are present in amounts that exceed the body’s needs?

26.84 How are the amino acids from protein “processed” when an

individual is in a state of starvation?

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Chapter 26 Protein Metabolism

A DD D IT IO NAL P R O BL L EM S 26.85 In which of the processes (1) urea cycle, (2) hemoglobin

catabolism, and (3) transamination reactions would each of the following molecules be encountered? a. Citrulline b. Carbon monoxide c. Pyruvate d. Urobilin 26.86 Characterize each of the following molecules as a possible reactant, product, or enzyme of (1) transamination, (2) oxidative deamination, or (3) both transamination and oxidative deamination. a. Arginine b. Glutamate c. a-Ketoglutarate d. Ammonium ion 26.87 Arrange the following events in the order in which they occur in the digestive process for proteins. (1) Peptide bonds are hydrolyzed with the help of pepsin. (2) Peptide bonds are hydrolyzed with the help of trypsin. (3) Large polypeptides pass from the stomach into the small intestine. (4) Amino acids pass through the intestinal wall into the bloodstream. 26.88 With the help of Figure 26.8 and the given conversion information, classify each of the following amino acids as (1) ketogenic but not glucogenic, (2) glucogenic but not ketogenic, (3) both ketogenic and glucogenic, or (4) neither ketogenic nor glucogenic. a. Alanine is converted to pyruvate. b. Aspartate is converted to either fumarate or oxaloacetate. c. Lysine is converted to acetoacetyl CoA. d. Isoleucine is converted to either succinyl CoA or acetyl CoA.

multiple-Choice Practice Test

Amino acid metabolism differs from that of carbohydrates and triacylglycerols in what way? a. There is no storage form for amino acids in the body. b. Amino acids cannot be used for energy production. c. Amino acids cannot be converted to acetyl CoA. d. All metabolic intermediates contain the element nitrogen. 26.94 Which of the following is not a use for the amino acids present in the body’s amino acid pool? a. Synthesis of proteins b. Synthesis of nonprotein nitrogen-containing substances c. Synthesis of nonessential amino acids d. Synthesis of essential amino acids 26.95 Which of the following is always one of the reactants in a transamination reaction? a. A keto acid b. Glycerol c. Ammonia d. Ammonium ion 26.96 Which of the following is always a reactant in an oxidative deamination reaction? a. Ammonium ion b. Water c. NADH d. A keto acid 26.93

26.89 Indicate whether each of the following statements refers to

transamination or deamination. a. Both an amino acid and a keto acid are reactants. b. An amino acid and water are reactants. c. The ammonium ion is a product. d. An amino acid is produced from a keto acid. 26.90 Which of the compounds (1) ornithine, (2) citrulline, (3) argininosuccinate, and (4) arginine is associated with each of the following urea cycle “occurrences”? a. Reacts with carbamoyl phosphate b. Reacts with water to produce urea c. Reacts with aspartate d. Fumarate is a product of its “breakup.” 26.91 Indicate whether each of the following statements is true or false. a. Glutamate is a very abundant amino acid in the amino acid pool. b. Pyruvate is a compound that participates in both the urea cycle and the citric acid cycle. c. Citrulline, a participant in the urea cycle, is a nonstandard amino acid. d. Glutamate is a reactant in oxidative deamination. 26.92 Which of the heme degradation products (1) bilirubin, (2) biliverdin, (3) stercobilin, and (4) urobilin is associated with each of the following heme degradation characterizations? a. CO is produced at the same time as this substance. b. The buildup of this substance in the blood produces jaundice. c. Molecular O2 is involved in the reaction that produces this substance. d. This degradation product gives feces its characteristic color.

Which of the following statements concerning the compound urea is incorrect? a. It is a white solid in the pure state. b. It is very soluble in water. c. It gives urine its odor and color. d. Two 9NH2 groups are present in its structure. 26.98 Which of the following compounds is not a reactant in the formation of carbamoyl phosphate? a. Carbon dioxide b. Urea c. Water d. Ammonium ion 26.99 In which of the following pairs of amino acids are both members of the pair nonstandard amino acids? a. Arginine and citrulline b. Arginine and ornithine c. Citrulline and ornithine d. Aspartate and glutamate 26.100 Which of the following statements concerning amino acid “carbon skeleton” degradation is correct? a. Each amino acid is degraded to a different product. b. All amino acids are degraded to the same product. 26.97

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Multiple-Choice Practice Test

c. Each amino acid is degraded by a different metabolic pathway. d. All glucogenic amino acids are degraded to the same product. 26.101 Which of the following is produced in the first step of the degradation of the heme portion of hemoglobin? a. Molecular O2 b. Carbon monoxide

c. Individual pyrrole groups d. Bilirubin 26.102 In which of the following is the compound pyridoxal phosphate encountered? a. The urea cycle b. Hemoglobin catabolism c. Transamination reactions d. Oxidative deamination reactions

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Answers to Selected Exercises Chapter 1 1.1 has mass, occupies space 1.3 (a) matter (b) matter (c) energy (d) energy (e) matter (f) matter 1.5 (a) shape (b) volume 1.7 (a) does not, yes (b) does, no (c) does, yes (d) does, yes 1.9 (a) physical (b) chemical (c) chemical (d) physical 1.11 (a) chemical (b) physical (c) chemical (d) physical 1.13 (a) physical (b) physical (c) chemical (d) physical 1.15 (a) chemical (b) physical (c) chemical (d) physical 1.17 (a) physical (b) physical (c) chemical (d) physical 1.19 (a) false (b) true (c) false (d) true 1.21 (a) heterogeneous mixture (b) homogeneous mixture (c) pure substance (d) heterogeneous mixture 1.23 (a) homogeneous mixture, one phase (b) heterogeneous mixture, two phases (c) heterogeneous mixture, three phases (d) heterogeneous mixture, three phases 1.25 (a) compound (b) compound (c) classification not possible (d) classification not possible 1.27 (a) A, classification not possible; B, classification not possible; C, compound (b) D, compound; E, classification not possible; F, classification not possible; G, classification not possible 1.29 (a) true (b) false (c) false (d) false 1.31 (a) true (b) false (c) false (d) false 1.33 (a) true (b) true (c) false (d) true 1.35 (a) more abundant (b) less abundant (c) less abundant (d) more abundant 1.37 (a) nitrogen (b) nickel (c) lead (d) tin 1.39 (a) Al (b) Ne (c) H (d) U 1.41 (a) Na, S (b) Mg, Mn (c) Ca, Cd (d) As, Ar 1.43 (a) no (b) yes (c) yes (d) no 1.45 (a) heteroatomic molecules (b) heteroatomic molecules (c) homoatomic molecules (d) heteroatomic molecules 1.47 (a) triatomic molecules (b) triatomic molecules (c) diatomic molecules (d) diatomic molecules 1.49 (a) compound (b) compound (c) element (d) compound 1.51 (a) true (b) false; Triatomic molecules must contain at least one kind of atom. (c) true (d) false; Both homoatomic and heteroatomic molecules may contain (b) (c) three or more atoms. 1.53 (a) (d) 1.55 (a) H2O (b) CO2 (c) O2 (d) CO 1.57 (a) compound (b) compound (c) element (d) element 1.59 (a) lithium, chlorine, oxygen (b) carbon, oxygen (c) cobalt (d) sulfur 1.61 (a) C12H22O11 (b) C8H10N4O2 1.63 (a) HCN (b) H2SO4 1.65 (a) BaCl2 (b) HNO3 (c) Na3PO4 (d) Mg(OH)2 1.67 (a) diagram I (b) diagram III (c) diagram II (d) diagrams I and IV 1.68 (a) diagram III (b) diagrams I and IV (c) diagram I (d) diagram III 1.69 (a) element (b) compound (c) mixture (d) compound 1.70 (a) homogeneous mixture (b) heterogeneous mixture (c) compound (d) compound 1.71 (a) element (b) mixture (c) mixture (d) compound 1.72 (a) changes 3 and 4 (b) changes 1 and 2 (c) change 2 (d) change 1 1.73 (a) B-ArBa-Ra (b) Eu-Ge-Ne (c) He-At-H-Er (d) Al-La-N 1.74 (a) same, both 4 (b) more, 6 and 5 (c) same, both 5 (d) fewer, 13 and 15 1.75 (a) 1  2  x  6; x  3 (b) 2  3  3x  17; x  4 (c) 1  x  x  5; x  2 (d) x  2x  x  8; x  2 1.76 (a) 2 (N2, NH3) (b) 4 (N, H, C, Cl) (c) 110; 5(2  6  4  5  5) (d) 56; 4(4  3  4  3) 1.77 b 1.78 a 1.79 c 1.80 c 1.81 d 1.82 d 1.83 c 1.84 b 1.85 d 1.86 c

Chapter 2 2.1 It is easier to use because it is decimal based. 2.3 (a) kilo (b) milli (c) micro (d) deci 2.5 (a) centimeter (b) kiloliter (c) microliter (d) nanogram 2.7 (a) nanogram, milligram, centigram (b) kilometer, megameter, gigameter (c) picoliter, microliter, deciliter (d) microgram, milligram, kilogram 2.9 60 minutes is a defined (exact) number and 60 feet is a measured (inexact) number. 2.11 (a) exact (b) exact (c) inexact (d) exact 2.13 (a) inexact (b) exact (c) exact (d) inexact 2.15 (a) 0.001 (b) 1 (c) 0.0001 (d) 10 2.17 (a) 0.1ºC (b) 0.01 mL (c) 1 mL (d) 0.1 mm 2.19 (a) between 40,000 and 60,000

(b) between 49,000 and 51,000 (c) between 49,900 and 50,100 (d) between 49,990 and 50,010 2.21 (a) 0.1 (b) 0.1 2.23 (a) 2.70 cm (b) 27 cm 2.25 (a) 4 (b) 1 or 4 (c) 2 (d) 3 2.27 (a) 4 (b) 2 (c) 4 (d) 3 (e) 5 (f) 4 2.29 (a) same (b) different (c) same (d) same 2.31 (a) the last zero (b) the 2 (c) the last 1 (d) the 4 (e) the last zero (f ) the last zero 2.33 (a) 0.001 (b) 0.0001 (c) 0.00001 (d) 100 (e) 0.001 (f) 0.00001 2.35 (a) 0.351 (b) 653,900 (c) 22.556 (d) 0.2777 2.37 (a) 2 (b) 2 (c) 2 (d) 2 2.39 (a) 0.0080 (b) 0.0143 (c) 14 (d) 0.182 (e) 1.1 (f) 5720 2.41 (a) 162 (b) 9.3 (c) 1261 (d) 20.0 2.43 (a) 1.207  102 (b) 3.4  103 (c) 2.3100  102 (d) 2.3  104 (e) 2.00  101 (f) 1.011  101 2.45 (a) 1.0  103 (b) 1.0  103 (c) 6.3  104 (d) 6.3  104 2.47 (a) two (b) three (c) three (d) four 2.49 (a) 5.50  1012 (b) 4.14  102 (c) 1.5  104 (d) 2.0  107 (e) 1.5  1011 (f) 1.2  106 2.51 (a) 102 (b) 104 (c) 104 (d) 104 2.53 (a) 1 day/24 hours, 24 hours/1 day (b) 10 decades/1 century, 1 century/10 decades (c) 3 feet/1 yard, 1 yard/3 feet (d) 4 quarts/1 gallon, 1 gallon/4 quarts 2.55 (a) 1 kL/103 L, 103 L/1 kL (b) 1 mg/103 g, 103 g/1 mg (c) 102 m/1 cm, 1 cm/102 m (d) 1 msec/106 sec, 106 sec/1 msec 2.57 (a) exact (b) inexact (c) exact (d) exact 2.59 (a) 1.6  102 m (b) 2.4  108 m (c) 3 m (d) 3.0  105 m 2.61 2.5 L 2.63 3.41 lb 2.65 0.0066 gal 2.67 183 lb, 6.30 ft 2.69 13.55 g/cm3 2.71 25.3 mL 2.73 243 g 2.75 (a) float (b) sink 2.77 274ºC 2.79 38.0F 2.81 10C 2.83 2.6 J/gC 2.85 0.155 cal/gC 2.87 (a) 48 cal (b) 8.40  102 cal (c) 180 cal 2.89 The first 12 is an exact number (no uncertainty), and the second 12 is an inexact number (contains uncertainty). 2.90 (a) 4.720506 (b) 4.7205 (c) 4.721 (d) 4.7 2.91 (a) 3.00  103 (b) 9.4  105 (c) 2.35  101 (d) 4.50000  108 2.92 (a) smaller, 103 (b) larger, 109 (c) smaller, 108 (d) smaller, 108 2.93 (a) four significant figures (b) four significant figures (c) three significant figures (d) exact 2.94 (a) 5.0  101 g/cm3 (b) 5.00  101 g/cm3 (c) 5.0000  101 g/cm3 (d) 5.000  101 g/cm3 2.95 (a) 1.3  102 mL (b) 81 mL (c) 9.88  104 mL (d) 5.51 mL 2.96 (a) 2.0 calories (b) 1.0 kilocalorie (c) 100 Calories (d) 1000 kilocalories 2.97 (a) 4.5  103 mg/L (b) 4.5  109 pg/mL (c) 4.5 g/L (d) 4.5 kg/m3 2.98 a 2.99 c 2.100 b 2.101 d 2.102 d 2.103 d 2.104 c 2.105 d 2.106 b 2.107 c

Chapter 3 3.1 (a) electron (b) neutron (c) proton (d) proton 3.3 (a) false (b) false (c) false (d) true 3.5 (a) 2 and 4 (b) 4 and 9 (c) 5 and 9 (d) 28 and 58 3.7 (a) 8, 8, and 8 (b) 8, 10, and 8 (c) 20, 24, and 20 (d) 100, 157, and 100 3.9 (a) atomic number (b) both atomic number and mass number (c) mass number (d) both atomic number and mass number 3.11 (a) 19 (b) 39 (c) 19 (d) 19 3.13 (a) nitrogen (b) aluminum (c) bar40 48 ium (d) gold 3.15 (a) 157N (b) 28 3.17 (a) S, Cl, Ar, 14Si (c) 18Ar (d) 22 Ti and K (b) Ar, K, Cl, and S (c) S, Cl, Ar, and K (d) S, (Cl, K), Ar 3.19 (a) 34 (b) 23 (c) 23 (d) 11 3.21 126C, 136C, 146C 3.23 (a) not isotopes (b) not isotopes (c) isotopes 3.25 (a) false (b) false (c) true (d) true 3.27 (a) not the same (b) same (c) not the same (d) same 3.29 (a) 6.95 amu (b) 24.31 amu 3.31 (a) 55.85 (b) 14.01 (c) calcium (d) iodine 3.33 (a) Ca (b) Mo (c) Li (d) Sn 3.35 (a) 6 (b) 28.09 amu (c) 39 (d) 9.01 amu 3.37 (a) K and Rb (b) P and As (c) F and I (d) Na and Cs 3.39 (a) group (b) periodic law (c) periodic law (d) group 3.41 (a) fluorine (b) sodium (c) krypton (d) strontium 3.43 (a) 3 (b) 4 (c) 4 (d) 4 3.45 (a) blue element (b) yellow element (c) yellow element (d) green element 3.47 (a) no (b) no (c) yes (d) yes 3.49 (a) S (b) P (c) I (d) Cl 3.51 (a) metal (b) nonmetal (c) metal (d) nonmetal

A-1

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Answers to Selected Exercises

(d) Br F

5.7 (a) 8 (b) 4 (c) 0 (d) 6 5.9 (a) NF3 (b) Cl2O

(c) H2S (d) CH4 5.11 (a) one triple bond (b) three single bonds (c) one double and two single bonds (d) one double and four single bonds 5.13 (a)S N q NS (b) H O C

A H

OO O OO H (d) H O O

C O H (c) H O C O H B A O H

5.15 (a) normal (b) normal (c) not normal (d) normal

S S S S S S S S S S S S S S S

5.17 (a) N (b) C (c) N (d) C 5.19 Oxygen forms three bonds instead of the normal two. 5.21 (a) nitrogen–oxygen (b) none present (c) oxygen– chlorine (d) two (oxygen–bromine) 5.23 (a) 20 (b) 8 (c) 8 (d) 24 SBrS O O P S H (b) SClSP SClS (c)SBrSSiSBrS (d)SQ F SO O SQ FS 5.25 (a) HSO O O SClS SBrS H SIS O SH O O 5.27 (a)SQ F SO S SQ F S (b) S I SCS I S (c) SBrSNSBrS (d) HSSe O O SBrS SIS S S

S S

S

S S S

H

S

5.29 (a) HS CSS C SS CSH (b) S F SNSSN S F S (c) HS CS C SSS NS S

4.41 (a) 2 extra electrons, 2 charge (b) 1 extra electron, 1 charge (c) 3 extra electrons, 3 charge (d) 2 extra electrons, 2 charge 4.43 (a) BaCl2 (b) BaBr2 (c) Ba3N2 (d) BaO 4.45 (a) MgF2 (b) BeF2 (c) LiF (d) AlF3 4.47 (a) Na2S (b) CaI2 (c) Li3N (d) AlBr3 4.49 (a) BeCl2 (b) BaI2 (c) Na2O (d) AlN 4.51 an extended array of alternating positive and negative ions 4.53 smallest whole-number repeating ratio of ions present 4.55 (a) diagram III (2:3 ratio) (b) diagram IV (1:2 ratio) (c) diagram I (3:1 ratio) (d) diagram II (1:1 ratio)

5.5 (a) Br Br (b) HS I S(c) I Br

ions; covalent: molecules

S S S S S S S S S S S S S S S

gain, or share electrons in such a way that they achieve a noble-gas electron configuration. 4.17 (a) O2 (b) Mg2 (c) F (d) Al3 4.19 (a) Ca2 (b) O2 (c) Na (d) Al3 4.21 (a) 15p, 18e (b) 7p, 10e (c) 12p, 10e (d) 3p, 2e 4.23 line 1: 18 electrons, 20 protons; line 2: Be, 3 4 protons; line 3: I, I; line 4: Al3, 10 electrons 4.25 (a) 146C (b) 27 13Al 35  52 (c) 17Cl (d) 24Cr 4.27 (a) 2 (b) 3 (c) 1 (d) 1 4.29 (a) 2 lost (b) 1 gained (c) 2 lost (d) 2 gained 4.31 (a) Ne (b) Ar (c) Ar (d) Ar 4.33 (a) Ne (b) Ar (c) Ar (d) Ar 4.35 (a) Group IIA (b) Group VIA (c) Group VA (d) Group IA 4.37 (a) 1s22s22p63s23p1 (b) 1s22s22p6 4.39 O S SO O S SO SS (a) Be OS (b) Mg Q Q KT SO FS OT Q NS (d) Ca (c) KT SO Q O SQ FS KT

Chapter 5 5.1 ionic: metal and nonmetal; covalent: two or more nonmetals 5.3 ionic: extended array of alternating positive and negative S S

M N 4.9 (a) Mg (b) K (c)SPN(d)SKrS 4.11 (a) Li (b) F (c) Be (d) N M of all elements. 4.15 They lose, N 4.13 They are the most unreactive

B

transfer and that for covalent bond formation is electron sharing. 4.3 (a) 2 (b) 2 (c) 3 (d) 4 4.5 (a) Group IA, 1 valence electron (b) Group VIIIA, 8 valence electrons (c) Group IIA, 2 valence electrons (d) Group VIIA, 7 valence electrons 4.7 (a) 1s22s22p2 (b) 1s22s22p5 (c) 1s22s22p63s2 (d) 1s22s22p63s23p3

O

Chapter 4 4.1 The mechanism for ionic bond formation is electron

4.57 all pairs except nitrogen and chlorine 4.59 Al2O3 and K2S 4.61 (a) potassium iodide (b) beryllium oxide (c) aluminum fluoride (d) sodium phosphide 4.63 (a) 1 (b) 2 (c) 4 (d) 2 4.65 (a) iron(II) oxide (b) gold(III) oxide (c) copper(II) sulfide (d) cobalt(II) bromide 4.67 (a) gold(I) chloride (b) potassium chloride (c) silver chloride (d) copper(II) chloride 4.69 (a) KBr (b) Ag2O (c) BeF2 (d) Ba3P2 4.71 (a) CoS (b) Co2S3 (c) SnI4 (d) Pb3N2 4.73 (a) SO42 (b) ClO3 (c) OH (d) CN 4.75 (a) PO43 and HPO42 (b) NO3 and NO2 (c) H3O and OH (d) CrO42 and Cr2O72 4.77 (a) NaClO4 (b) Fe(OH)3 (c) Ba(NO3)2 (d) Al2(CO3)3 4.79 line 1: NH4CN, NH4NO3, NH4HCO3, (NH4)2SO4; line 2: Al(CN)3, Al(NO3)3, Al(HCO3)3, Al2(SO4)3; line 3: AgCN, AgHCO3, Ag2SO4; line 4: Ca(CN)2, Ca(NO3)2, Ca(HCO3)2, CaSO4 4.81 (a) magnesium carbonate (b) zinc sulfate (c) beryllium nitrate (d) silver phosphate 4.83 (a) iron(II) hydroxide (b) copper(II) carbonate (c) gold(I) cyanide (d) manganese(II) phosphate 4.85 (a) KHCO3 (b) Au2(SO4)3 (c) AgNO3 (d) Cu3(PO4)2 4.87 line 1: Mg2, OH, Mg(OH)2; line 2: Ba2, Br, barium bromide; line 3: Zn(NO3)2, zinc nitrate; line 4: Fe3, ClO3, Fe(ClO3)3; line 5: Pb4, O2, lead(IV) oxide; line 6: Co3(PO4)2, cobalt(II) phosphate; line 7: KI, potassium iodide; line 8: Cu, SO42, copper(I) sulfate; line 9: Li, N3, Li3N; line 10: Al2S3, aluminum sulfide 4.88 line 1: 26, 33, 23, 3 197 2 18  4.89 (a) Na 3; line 2: 59 28 Ni , 3; line 3: 77 Ir , 75; line 4: 9 F , 9 (b) F (c) S2 (d) Ca2 4.90 (a) XZ2 (b) X2Z (c) XZ (d) XZ 4.91 (a) S (b) Mg (c) P (d) Al 4.92 (a) only monatomic ions (b) both monatomic and polyatomic ions (c) only polyatomic ions (d) only monatomic ions 4.93 (a) K, Cl (b) Ca2, S2 (c) Be2, two F (d) two Al3, three S2 4.94 (a) Na3N, sodium nitride (b) KNO3, potassium nitrate (c) MgO, magnesium oxide (d) (NH4)3PO4, ammonium phosphate 4.95 (a) tin(IV) chloride, tin(II) chloride (b) iron(II) sulfide, iron(III) sulfide (c) copper(I) nitride, copper(II) nitride (d) nickel(II) iodide, nickel(III) iodide 4.96 (a) same (3) (b) different (1 and 2) (c) different (1 and 3) (d) different (2 and 1) 4.97 (a) copper(I) nitrate, copper(II) nitrate (b) lead(II) phosphate, lead(IV) phosphate (c) manganese(III) cyanide, manganese(II) cyanide (d) cobalt(II) chlorate, cobalt(III) chlorate 4.98 (a) Na2S (b) Na2SO4 (c) Na2SO3 (d) Na2S2O3 4.99 a 4.100 d 4.101 d 4.102 c 4.103 a 4.104 b 4.105 a 4.106 d 4.107 c 4.108 a

O

3.53 (a) metal (b) nonmetal (c) poor conductor of electricity (d) good conductor of heat 3.55 (a) orbital (b) orbital (c) shell (d) shell 3.57 (a) true (b) true (c) false (d) true 3.59 (a) 2 (b) 2 (c) 6 (d) 18 3.61 (a) 1s22s22p2 (b) 1s22s22p63s1 (c) 1s22s22p63s23p4 (d) 1s22s22p63s23p6 3.63 (a) oxygen (b) neon (c) aluminum (d) calcium 3.65 (a) 1s22s22p63s23p5 (b) 1s22s22p63s23p64s23d104p65s24 d7 (c) 1s22s22p63s23p64s2 (d) 1s22s22p63s23p64s23d1 3.67 (a) { { u u (b) { { {{{ { (c) { { {{{ { u u u (d) { { {{{ { {{{ { {{ u u u 3.69 (a) 3 (b) 0 (c) 1 (d) 5 3.71 (a) no (b) yes (c) no (d) yes 3.73 (a) s area (b) d area (c) p area (d) d area 3.75 (a) p1 (b) d 3 (c) s2 (d) p6 3.77 (a) s area (b) d area (c) p4 element (d) s2 element 3.79 (a) representative element (b) noble gas (c) transition element (d) inner transition element 3.81 (a) noble gas (b) representative element (c) transition element (d) representative element 3.83 (a) 4 (b) 1 (c) 2 (d) 6 3.85 (a) helium, 2, 3, 2, 1 (b) 60 28 Ni, 28, 28, 32 90 (c) argon, 37 18 Ar, 18, 19 (d) strontium, 38 Sr, 38, 38 (e) uranium, 92, 235, 92, 232 143 (f) chlorine, 37 17 Cl, 17, 37 (g) plutonium, 94 Pu, 94, 138 (h) sulfur, 16, 40 44 211 32, 16, 16 (i) 56 26 Fe, 26, 26, 30 (j) 20 Ca, 20, 40, 20 3.86 (a) 20 Ca (b) 86 Rn 110 9 (c) 47 Ag (d) 4 Be 3.87 (a) same number of neutrons, 7 (b) same number of neutrons, 10 (c) same total number of subatomic particles, 54 (d) same number of electrons, 17 3.88 (a) same (b) different (c) different (d) 50 55 65 3.90 1638 electrons same 3.89 (a) 57 24 Cr (b) 24 Cr (c) 24 Cr (d) 24 Cr 3.91 (a) Be, Al (b) Be, Al, Ag, Au (the metals) (c) N, Be, Ar, Al, Ag, Au (d) Ag, Au 3.92 the same 3.93 (a) 1s22s22p1 (B) (b) 1s22s22p63s23p1 (Al) (c) 1s22s1 (Li) (d) 1s22s22p63s23p3 (P) 3.94 (a) 8O (b) 10Ne (c) 30Zn (d) 3.95 a 3.96 c 3.97 b 3.98 d 3.99 a 3.100 c 3.101 b 12Mg 3.102 b 3.103 d 3.104 d

OS

A-2

H

H

H

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Answers to Selected Exercises

H

S

S S

H

H

H

S S S S S S S SClS



(c) SSClSAlSClS (d) SClS

(b) 3 K

2

OS H 5.31 (a) SSOSH (b) H SBe Q

(d) HS CS C SSS CSH



O SO NSO OS Q QS Q Q SQ O

OS SO OSO SO P SO OS Q Q Q SO QS



5.33 (a) Na+ S C SSS N S 

3

5.35 (a) linear (b) angular

(c) tetrahedral (d) linear 5.37 (a) angular (b) angular (c) angular (d) linear 5.39 (a) trigonal pyramidal (b) trigonal planar (c) tetrahedral (d) tetrahedral 5.41 (a) trigonal pyramidal (b) tetrahedral (c) angular (d) angular 5.43 (a) trigonal planar about each carbon atom (b) tetrahedral about carbon atom and angular about oxygen atom 5.45 (a) Na, Mg, Al, P (b) I, Br, Cl, F (c) Al, P, S, O (d) Ca, Mg, C, O 5.47 (a) N, O, Cl, F, Br (b) Na, K, Rb, (c) F, O, Cl, N (d) 0.5 units d1

d2

d1

d2

d2

d1

d2

d1

5.49 (a) B O N (b) CIO F (c) N O C (d) F O O 5.51 (a) H—Br, H—Cl, H—O (b) O—F, P—O, Al—O (c) Br—Br, H—Cl, B—N (d) P—N, S—O, Br—F 5.53 (a) polar covalent (b) ionic (c) nonpolar covalent (d) ionic 5.55 (a) nonpolar (b) polar (c) polar (d) polar 5.57 (a) nonpolar (b) polar (c) polar (d) polar 5.59 (a) polar (b) polar (c) nonpolar (d) polar 5.61 (a) sulfur tetrafluoride (b) tetraphosphorus hexoxide (c) chlorine dioxide (d) hydrogen sulfide 5.63 (a) diagram I (b) diagram II (c) diagram IV (d) diagram III 5.65 (a) ICl (b) N2O (c) NCl3 (d) HBr 5.67 (a) H2O2 (b) CH4 (c) NH3 (d) PH3 5.69 (a) 26 (b) 24 (c) 14 (d) 8 5.70 (a) same, both single (b) different, double and single (c) same, both triple (d) same, both single 5.71 (a) not enough electron dots (b) not enough electron dots (c) improper placement of a correct number of electron dots (d) too many electron dots 5.72 (a) tetrahedral; tetrahedral (b) tetrahedral; tetrahedral (c) trigonal planar; angular (d) trigonal planar; trigonal planar 5.73 (a) can’t classify (b) nonpolar (c) can’t classify (d) polar 5.74 (a) BrI (b) SO2 (c) NF3 (d) H3CF 5.75 BA, CA, DB, DA 5.76 (a)

H A H O COH, A H

H A H O CO O F S, A O H

SO FS A H O CO O F S, A O H

SO SO FS FS A A O O H O CO F S, S F O CO O FS A O O A O SFS SFS O O

(b) all are tetrahedral (c) nonpolar, polar, polar, polar, nonpolar 5.77 Chemical formulas for molecular compounds are written with the least electronegative atom first; N is the least electronegative atom 5.78 NaNO3 is an ionic compound; the ions present are sodium ion and nitrate ion. 5.79 (a) sodium chloride (b) bromine monochloride (c) potassium sulfide (d) dichlorine monoxide 5.80 d 5.81 c 5.82 b 5.83 b 5.84 d 5.85 b 5.86 c 5.87 c 5.88 c 5.89 d

Chapter 6 6.1 (a) 342.34 amu (b) 100.23 amu (c) 183.20 amu (d) 132.17 amu 6.3 (a) 6.02  1023 apples (b) 6.02  1023 elephants (c) 6.02  1023 Zn atoms (d) 6.02  1023 CO2 molecules 6.5 (a) 9.03  1023 atoms Fe (b) 9.03  1023 atoms Ni (c) 9.03  1023 atoms C (d) 9.03  1023 atoms Ne 6.7 (a) 0.200 mole (b) Avogadro’s number (c) 1.50 moles (d) 6.50  1023 atoms 6.9 (a) 28.01 g (b) 44.01 g (c) 58.44 g (d) 342.34 g 6.11 (a) 6.7 g (b) 3.7 g (c) 48.0 g (d) 96.0 g 6.13 (a) 0.179 mole (b) 0.114 mole (c) 0.0937 mole (d) 0.0210 mole 2 moles H 1 mole H 2SO 4 1 mole S 6.15 (a)     1 mole H 2SO 4 2 moles H 1 mole H 2SO 4 1 mole H 2SO 4 4 moles O 1 mole H 2SO 4     1 mole S 1 mole H 2SO 4 4 moles O (b)

1 mole POCl3 1 mole P 1 mole O     1 mole POCl3 1 mole P 1 mole POCl3

1 mole POCl3 3 moles Cl 1 mole POCl3     1 mole O 1 mole POCl3 3 moles Cl

A-3

6.17 (a) 2.00 moles S, 4.00 moles O (b) 2.00 moles S, 6.00 moles O (c) 3.00 moles N, 9.00 moles H (d) 6.00 moles N, 12.0 moles H 6.19 (a) 16.0 moles of atoms (b) 14.0 moles of atoms (c) 45.0 moles of atoms (d) 15.0 moles of atoms 3 moles H 4 moles O 6.21 (a) (b) 1 mole H 3PO 4 1 mole H 3PO 4 8 moles atoms 4 moles O (d) 1 mole H 3PO 4 1 mole P 6.23 (a) 5.57  1023 atoms (b) 4.81  1023 atoms (c) 6.0  1022 atoms (d) 3.0  1023 atoms 6.25 (a) 63.6 g (b) 31.8 g (c) 5.88  1020 g (d) 1.06  1022 g 6.27 (a) 2.50 moles (b) 0.227 mole (c) 6.6  1014 mole (d) 6.6  1014 mole 6.29 (a) 6.14  1022 atoms S (b) 1.50  1023 atoms S (c) 3.61  1023 atoms S (d) 2.41  1024 atoms S 6.31 (a) 32.1 g S (b) 6.39  1022 g S (c) 64.1 g S (d) 1150 g S 6.33 (a) balanced (b) balanced (c) not balanced (d) balanced 6.35 (a) 4 N, 6 O (b) 10 N, 12 H, 6 O (c) 1 P, 3 Cl, 6 H (d) 2 Al, 3 O, 6 H, 6 Cl 6.37 (a) 2Na  2H2O : 2NaOH  H2 (b) 2Na  ZnSO4 : Na2SO4  Zn (c) 2NaBr  Cl2 : 2NaCl  Br2 (d) 2ZnS  3O2 : 2ZnO  2SO2 6.39 (a) CH4  2O2 : CO2  2H2O (b) 2C6H6  15O2 : 12CO2  6H2O (c) C4H8O2  5O2 : 4CO2  4H2O (d) C5H10O  7O2 : 5CO2  5H2O 6.41 (a) 3PbO  2NH3 : 3Pb  N2  3H2O (b) 2Fe(OH)3  3H2SO4 : Fe2(SO4)3  6H2O 6.43 (a) A2  3B2 : 2AB3 (b) A2  B2 : 2AB 6.45 diagram III 2 moles Ag 2CO 3 2 moles Ag 2CO 3 2 moles Ag 2CO 3 6.47      4 moles Ag 2 moles CO 2 1 mole O 2 (c)

4 moles Ag 4 moles Ag 2 moles CO 2     1 mole O 2 2 moles CO 2 1 mole O 2 The other six are the reciprocals of these six factors. 6.49 (a) 14.0 moles CO2 (b) 1.00 mole CO2 (c) 4.00 moles CO2 (d) 2.00 moles CO2 3 moles H 2S 6 moles HCl 6.51 (a) (b) 2 moles SbCl3 1 mole Sb 2S 3 2 moles SbCl3 6 moles HCl (d) 3 moles H 2S 1 mole Sb 2S 3 6.53 8 water molecules 6.55 (a) CO2 and H2O (b) 6.0 moles CO2 and 12 moles H2O 6.57 (a) 24.3 g NH3 (b) 1.80  102 g (NH4)2Cr2O7 (c) 22.9 g N2H4 (d) 24.3 g NH3 6.59 5.09 g O2 6.61 14.3 g O2 6.63 5.63 g H2O 6.65 y  8 6.66 (a) 1.00 mole S8 (b) 28.0 g Al (c) 30.0 g Mg (d) 6.02  1023 atoms He 6.67 (a) 0.03560 mole SiH4 (b) 2.139 g SiO2 (c) 2.144  1022 molecules (CH3)3SiCl (d) 2.144  1022 atoms Si 6.68 59.0 g Si 6.69 C4H6 6.70 8.33 g N2, 21.4 g H2O, and 45.2 g Cr2O3 6.71 109 g Ag and 16.2 g S 6.72 43.4 g Be 6.73 d 6.74 b 6.75 b 6.76 d 6.77 a 6.78 b 6.79 b 6.80 b 6.81 b 6.82 c (c)

Chapter 7 7.1 (a) potential energy (b) magnitude increases as temperature increases (c) cause order within the system (d) electrostatic attractions 7.3 (a) liquid state (b) solid state (c) gaseous state (d) solid state 7.5 (a) gaseous state (b) solid state (c) liquid state (d) solid and liquid states 7.7 (a) amount (b) volume (c) pressure (d) temperature 7.9 (a) 0.967 atm (b) 403 mm Hg (c) 403 torr (d) 0.816 atm 7.11 7.2 atm 7.13 2.71 L 7.15 diagram II 7.17 3.64 L 7.19 144C 7.21 diagram II P 1V 1T 2 P 1V 1T 2 P 2V 2T 1 7.23 (a) T 1 5 (b) P 2 5 (c) V 1 5 P 2V 2 V 2T 1 P 1T 2 7.25 (a) 5.90 L (b) 2.11 atm (c) 171C (d) 3.70  103 mL 7.27 diagram II 7.29 209C 7.31 1.12 L 7.33 (a) 4.11 L (b) 3.16 atm (c) 98C (d) 16,300 mL 7.35 0.42 atm 7.37 98 mm Hg 7.39 (a) 2.4 atm (b) 2.4 atm (c) 1.2 atm 7.41 (a) endothermic (b) endothermic (c) exothermic 7.43 (a) no (b) yes (c) yes 7.45 amount of liquid decreases; temperature of liquid decreases 7.47 rate increases 7.49 (a) true (b) true 7.51 the higher the temperature, the higher the vapor pressure 7.53 volatile 7.55 (a) true (b) true

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A-4

Answers to Selected Exercises

(c) false (d) false 7.57 the higher the external pressure, the higher the boiling point 7.59 Molecules must be polar. 7.61 Boiling point increases as intermolecular force strength increases. 7.63 (a) London (b) hydrogen bonding (c) dipole–dipole (d) London 7.65 (a) no (b) yes (c) yes (d) no 7.67 four (see Figure 7.21) 7.69 (a) 0.871 atm (b) 298⬚C (c) 869⬚C 7.70 (a) 915⬚C (b) ⫺199⬚C (c) 24⬚C (d) 172⬚C 7.71 (a) Boyle’s law, Charles’s law and combined gas law (b) Charles’s law (c) Boyle’s law (d) Boyle’s law 7.72 8.08 ⫻ 106 L He 7.73 (a) 4.6 atm (b) 29 atm (c) 0.14 atm (d) 0.90 atm 7.74 5.37 ⫻ 1022 molecules H2S 7.75 24.7 L 7.76 0.22 g N2 7.77 (a) 1.00 atm (b) 1.00 atm (c) 1.50 atm (He), 1.00 atm (Ne), 0.50 atm (Ar) (d) 0.50 atm (He), 1.00 atm (Ne), 1.50 atm (Ar) 7.78 (a) boils (b) does not boil (c) does not boil (d) does not boil 7.79 (a) PBr3 (b) PI3 (c) PI3 7.80 (a) Br2, larger mass (b) H2O, hydrogen bonding (c) CO, dipole–dipole (d) C3H8, larger size 7.81 a 7.82 d 7.83 d 7.84 a 7.85 b 7.86 a 7.87 d 7.88 d 7.89 d 7.90 a

Chapter 8 8.1 (a) true (b) true (c) true (d) false 8.3 (a) solute: sodium chloride; solvent: water (b) solute: sucrose; solvent: water (c) solute: water; solvent: ethyl alcohol (d) solute: ethyl alcohol; solvent: methyl alcohol 8.5 (a) first solution (b) first solution (c) first solution (d) second solution 8.7 (a) supersaturated (b) saturated (c) saturated (d) unsaturated 8.9 (a) saturated (b) unsaturated (c) unsaturated (d) saturated 8.11 (a) dilute (b) concentrated (c) dilute (d) concentrated 8.13 (a) hydrated ion (b) hydrated ion (c) oxygen atom (d) hydrogen atom 8.15 (a) decrease (b) increase (c) increase (d) increase 8.17 (a) slightly soluble (b) very soluble (c) slightly soluble (d) slightly soluble 8.19 (a) ethanol (b) carbon tetrachloride (c) ethanol (d) ethanol 8.21 (a) soluble with exceptions (b) soluble (c) insoluble with exceptions (d) soluble 8.23 (a) all are soluble (b) all are soluble (c) CaBr2, Ca(OH)2, CaCl2 (d) NiSO4 8.25 (a) diagram IV (b) diagrams I and III 8.27 (a) 7.10%(m/m) (b) 6.19%(m/m) (c) 9.06%(m/m) (d) 0.27%(m/m) 8.29 (a) 3.62 g (b) 14.5 g (c) 68.8 g (d) 124 g 8.31 0.6400 g 8.33 276 g 8.35 (a) 4.21%(v/v) (b) 4.60%(v/v) 8.37 18%(v/v) 8.39 (a) 2.0%(m/v) (b) 15%(m/v) 8.41 0.500 g 8.43 3.75 g 8.45 (a) 6.0 M (b) 0.456 M (c) 0.342 M (d) 0.500 M 8.47 (a) 273 g (b) 0.373 g (c) 136 g (d) 88 g 8.49 (a) 85.6 mL (b) 2.64 mL (c) 9180 mL (d) 0.24 mL 8.51 (a) 0.183 M (b) 0.0733 M (c) 0.0120 M (d) 0.00275 M 8.53 (a) 1450 mL (b) 18.0 mL (c) 85,600 mL (d) 7.5 mL 8.55 (a) 3.0 M (b) 3.0 M (c) 4.5 M (d) 1.5 M 8.57 diagram II 8.59 (a) suspension (b) suspension (c) true solution and colloidal dispersion (d) true solution 8.61 (a) false (b) false (c) false (d) true 8.63 The presence of solute molecules decreases the ability of solvent molecules to escape. 8.65 It is a more concentrated solution and thus has a lower vapor pressure. 8.67 diagram III 8.69 (a) same as (b) greater than (c) less than (d) greater than 8.71 2 to 1 8.73 (a) swell (b) remain the same (c) swell (d) shrink 8.75 (a) hemolyze (b) remain unaffected (c) hemolyze (d) crenate 8.77 (a) hypotonic (b) isotonic (c) hypotonic (d) hypertonic 8.79 (a) decrease (b) increase (c) not change (d) decrease 8.81 (a) K⫹ and Cl⫺ leave the bag. (b) K⫹, Cl⫺, and glucose leave the bag. 8.83 (a) like (both soluble) (b) unlike (c) unlike (d) like (both insoluble) 8.84 (a) 4.02 g (b) 7.303 g (c) 12.6 g (d) 0.148 g 8.85 0.0700 qt 8.86 (a) 7.1 L (b) 9.5 L (c) 11 L (d) 14 L 8.87 (a) 0.472 M (b) 0.708 M (c) 1.04 M (d) 1.60 M 8.88 (a) 37.5%(m/v) (b) 2.23 M 8.89 (a) 4.00 M (b) 3.22 M 8.90 (a) NaCl (b) MgCl2 8.91 c 8.92 b 8.93 d 8.94 b 8.95 b 8.96 d 8.97 b 8.98 d 8.99 c 8.100 b

Chapter 9 9.1 (a) X 1 YZ ¡ Y 1 XZ (b) X 1 Y ¡ XY 9.3 (a) single-replacement (b) decomposition (c) double-replacement (d) combination 9.5 (a) combination, single-replacement, combustion (b) decomposition, single-replacement (c) combination, decomposition, single-replacement, double-replacement, combustion (d) combination, decomposition, single-replacement, double-replacement, combustion 9.7 (a) ⫹2 (b) ⫹6 (c) 0 (d) ⫹5 9.9 (a) ⫹3 (b) ⫹4 (c) ⫹6 (d) ⫹6 (e) ⫹6 (f) ⫹6 (g) ⫹6 (h) ⫹5 9.11 (a) ⫹3P, ⫺1F (b) ⫹1Na, ⫺2O, ⫹1H (c) ⫹1Na, ⫹6S, ⫺2O (d) ⫹4C, ⫺2O 9.13 (a) redox (b) nonredox (c) redox (d) redox 9.15 (a) H2 oxidized, N2 reduced (b) KI oxidized, Cl2 reduced (c) Fe oxidized, Sb2O3 reduced (d) H2SO3 oxidized, HNO3 reduced 9.17 (a) N2 oxidizing agent, H2 reducing agent (b) Cl2 oxidizing agent, KI reducing agent (c) Sb2O3 oxidizing agent, Fe reducing agent (d) HNO3 oxidizing agent, H2SO3 reducing agent 9.19 molecular collisions, activation energy, and collision orientation 9.21 total kinetic energy of colliding reactants; collision orientation 9.23 (a) exothermic (b) endothermic (c) endothermic (d) exothermic 9.25 (a) exothermic (b) released 9.27 c a d

b

9.29 (a) As temperature increases, so does the number of collisions per second. (b) A catalyst lowers the activation energy. 9.31 The concentration of O2 has increased from 21% to 100%. 9.33 (a) increase (b) decrease (c) increase (d) decrease 9.35 No catalyst Catalyst

9.37 (a) 1 (b) 3 (c) 4 (d) 3 9.39 rate of forward reaction ⫽ rate of reverse reaction 9.41 (a) N 2 1g2 1 O 2 1g2 ¡ 2NO1g2 (b) 2NO1g2 ¡ N 2 1g2 1 O 2 1g2 9.43 Products

Reactants 9.45 Yes, the concentrations of molecules in diagrams III and IV are the same. 9.47 Diagrams II and IV; diagram III cannot be produced from the original mixture. 3 NO 2 4 2 3 Cl2 4 3 CO 4 (b) K eq 5 9.49 (a) K eq 5 3 N 2O 4 4 3 COCl2 4 (c) K eq 5

3 CH 4 4 3 H 2S 4 2 3 CS 2 4 3 H 2 4

4

9.51 (a) Keq ⫽ [SO3] (c) K eq 5

3 NaCl 4 2 3 Na 2SO 4 4 3 BaCl2 4

(d) K eq 5 (b) K eq 5

3 SO 3 4 2 3 O 2 4 3 SO 2 4 2 1 3 Cl2 4

(d) Keq ⫽ [O2]

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Answers to Selected Exercises

9.53 4.8  105 9.55 (a) more products than reactants (b) essentially all reactants (c) significant amounts of both reactants and products (d) significant amounts of both reactants and products 9.57 diagram IV 9.59 diagram IV 9.61 (a) right (b) left (c) left (d) right 9.63 (a) left (b) left (c) left (d) left 9.65 (a) left (b) no effect (c) right (d) no effect 9.67 endothermic reaction 9.69 (a) redox, single replacement (b) redox, combustion (c) redox, decomposition (d) nonredox, double replacement 9.70 (a) redox (b) redox (c) redox (d) can’t classify 9.71 (a) gain (b) reduction (c) decrease (d) increase 9.72 (a) gains (b) loses (c) loses (d) gains 9.73 (a) decrease (b) increase (c) increase (d) decrease 9.74 (a)# no (b) no (c) yes (d) no 9.75 CS 2 1g2 1 4H 2 1g2 Δ CH 4 1g2 1 2H 2S1g2 9.76 (a) yes (b) yes (c) no (d) yes 9.77 (a) no effect (b) right (c) right (d) right 9.78 c 9.79 c 9.80 a 9.81 b 9.82 c 9.83 b 9.84 c 9.85 d 9.86 b 9.87 d

Chapter 10 10.1 (a) H (b) OH 10.3 (a) Arrhenius acid H2O H2O (b) Arrhenius base 10.5 (a) HI 9: H  I (b) HClO 9: H  ClO H2O H2O (c) LiOH 9: Li  OH (d) CsOH 9: Cs  OH 10.7 (a) acid (b) base (c) acid (d) acid 10.9 (a) HClO  H2O : H3O  ClO (b) HClO4  NH3 : NH4  ClO4 (c) H3O  OH : H2O  H2O (d) H3O  NH2 : H2O  NH3 10.11 (a) HSO3 (b) HCN (c) C2O42 (d) H2PO4 10.13 (a) HS  H2O : H3O  S2, HS  H2O : H2S  OH (b) HPO42  H2O : H3O  PO43, HPO42  H2O : H2PO4  OH (c) NH3  H2O : H3O  NH2, NH3  H2O : NH4  OH (d) OH  H2O : H3O  O2, OH  H2O : H2O  OH 10.15 (a) monoprotic (b) diprotic (c) monoprotic (d) diprotic 10.17 H3C6H5O7  H2O : H3O  H2C6H5O7, H2C6H5O7  H2O : H3O  HC6H5O72, HC6H5O72  H2O : H3O  C6H5O73 10.19 (a) 1, 0 (b) 2, 4 (c) 1, 7 (d) 0, 4 10.21 To show that it is a monoprotic acid 10.23 Monoprotic; only one H atom is involved in a polar bond. 10.25 (a) strong (b) weak (c) weak (d) strong 10.27 The equilibrium position is far to the right for strong acids and far to the left for weak acids. 10.29 0.10 M in both H3O and Cl ions and zero in HCl 10.31 acid in diagram IV 10.33 (a) K a 5 10.35 (a) K b 5

3H1 4 3F2 4 3 HF 4 3 NH 41 4 3 OH 2 4 3 NH 3 4

(b) K a 5

3 H 1 4 3 C 2H 3O 22 4 3 HC 2H 3O 2 4

(b) K b 5

3 C 6H 5NH 31 4 3 OH 2 4 3 C 6H 5NH 2 4

10.37 (a) H3PO4 (b) HF (c) H2CO3 (d) HNO2 10.39 4.9  105 10.41 (a) acid (b) salt (c) salt (d) base 10.43 (a) base (b) salt (c) acid H2O H2O (d) salt 10.45 (a) Ba(NO3)2 9: Ba2  2NO3 (b) Na2SO4 9: H2O H2O 2  2  2Na  SO4 (c) CaBr2 9: Ca  2Br (d) K2CO3 9: 2K  CO32 10.47 (a) no (b) yes (c) yes (d) no 10.49 (a) 1 to 1 (b) 1 to 2 (c) 1 to 1 (d) 2 to 1 10.51 (a) HCl  NaOH : NaCl  H2O (b) HNO3  KOH : KNO3  H2O (c) H2SO4  2LiOH : Li2SO4  2H2O (d) 2H3PO4  3Ba(OH)2 : Ba3(PO4)2  6H2O 10.53 (a) H2SO4  2LiOH : Li2SO4  2H2O (b) HCl  NaOH : NaCl  H2O (c) HNO3  KOH : KNO3  H2O (d) 2H3PO4  3Ba(OH)2 : Ba3(PO4)2  6H2O 10.55 (a) 3.3  1012 M (b) 1.5  109 M (c) 1.1  107 M (d) 8.3  104 M 10.57 (a) acidic (b) basic (c) basic (d) acidic 10.59 line 1: 4.5  1013, acidic; line 2: 3.0  1012, basic; line 3: 1.5  107, basic; line 4: 1.4  107, acidic 10.61 (a) 4.00 (b) 11.00 (c) 11.00 (d) 7.00 10.63 (a) 7.68 (b) 7.40 (c) 3.85 (d) 11.85 10.65 (a) 1  102 (b) 1  106 (c) 1  108 (d) 1  1010 10.67 (a) 2.1  104 M (b) 8.1  106 M (c) 4.5  108 M (d) 3.6  1013 M 10.69 line 1: 6.2  108, 1.6  107, basic; line 2: 1.4  105, 9.14, basic; line 3: 5.0  106, 2.0  109, acidic; line 4: 1.4  105, 4.85, acidic 10.71 (a) 3.35 (b) 6.37 (c) 7.21 (d) 1.82 10.73 acid B 10.75 (a) strong acid–strong base salt (b) weak acid–strong base salt (c) strong acid–weak base salt (d) strong acid–strong base salt 10.77 (a) none (b) C2H3O2 (c) NH4 (d) none 10.79 (a) neutral (b) basic (c) acidic (d) neutral 10.81 (a) no (b) yes

A-5

(c) no (d) yes 10.83 (a) HCN and CN (b) H3PO4 and H2PO4 (c) H2CO3 and HCO3 (d) HCO3 and CO32 10.85 (a) F  H3O : HF  H2O (b) H2CO3  OH : HCO3  H2O (c) CO32  H3O : HCO3  H2O (d) H3PO4  OH : H2PO4  H2O 10.87 all four diagrams 10.89 7.06 10.91 5.17 10.93 (a) weak (b) strong (c) strong (d) strong 10.95 (a) both (b) molecules (c) ions (d) both 10.97 (a) 2 (b) 3 (c) 3 (d) 2 10.99 (a) NaCl : Na  Cl (b) Mg(NO3)2 : Mg2  2NO3 (c) K2S : 2K  S2 (d) NH4CN : NH4  CN 10.101 diagram 3 10.103 (a) 1 Eq (b) 1 Eq (c) 2 Eq (d) 1 Eq 10.105 (a) 2 Eq (b) 3 Eq (c) 4 Eq (d) 14 Eq 10.107 0.094 mole Cl ion 10.109 21 mg Ca2 ion 10.111 (a) 0.0500 M (b) 0.800 M (c) 0.950 M (d) 0.120 M 10.113 (a) yes (b) no (c) no (d) yes 10.114 (a) no (b) yes, both strong (c) no (d) yes, both weak 10.115 (a) solution A, solution D, solution C, solution B (b) solution B, solution C, solution D, solution A (c) solution B, solution C, solution D, solution A (d) solution A, solution D, solution C, solution B 10.116 7.0 10.117 HCl, HCN, KCl, NaOH 10.118 (a) HCN and KCN (b) HF and NaF 10.119 H3PO4/H2PO4 and H2PO4/HPO42 10.120 CN ion undergoes hydrolysis to a greater extent than NH4 ion, resulting in a basic solution; NH4 ion and C2H3O2 ion hydrolyze to an equal extent, resulting in a neutral solution. 10.121 0.0035 g NaOH 10.122 a 10.123 d 10.124 b 10.125 c 10.126 b 10.127 a 10.128 d 10.129 b 10.130 a 10.131 d 96 Chapter 11 11.1 (a) 104Be, Be-10 (b) 25 11Na, Na-25 (c) 41Nb, Nb-96

(d) 257 11.3 (a) 147N (b) 197 79Au (c) Sn-121 (d) B-10 103 Lr, Lr-257 11.5 the spontaneous emission of radiation from the nucleus of the atom 11.7 approximately 1-to-1 ratio for low-atomic-numbered stable nuclei and 3-to-2 ratio for higher-atomic-numbered stable nuclei 11.9 (a) 42a 4 (b)10b (c) 00g 11.11 2 protons and 2 neutrons 11.13 (a) 200 84 Po : 2a 4 240 4 236 244 4 240 238  196 82Pb (b) 96Cm : 2a  94Pu (c) 96Cm : 2a  94Pu (d) 92U : 2a 0 0 234 10 10 14 14 21  90Th 11.15 (a) 4Be : 1b  5B (b) 6C : 1b  7N (c) 9F : 0 0 21 25 25 11.17 A : A  4, Z : Z  2 1b  10Ne (d) 11Na : 1b  12Mg 4 200 11.19 (a) 10b (b) 28 11.21 (a) 42a (b) 10b 12Mg (c) 2a (d) 80Hg 1 1 1 11.23 diagram I 11.25 (a) 4 (b) 64 (c) 8 (d) 641 11.27 (a) 1.4 days (b) 0.90 day (c) 0.68 day (d) 0.54 day 11.29 0.250 g 11.31 three 4 half-lives 11.33 2000 11.35 92 11.37 (a) 42a (b) 25 12Mg (c) 2a 1 (d) 1p 11.39 Termination of a decay series requires a stable nuclide. 0 0 4 228 228 228 228 228 11.41 232 90Th : 2a  88Ra, 88Ra : 1b  89Ac, 89Ac : 1b  90Th, 228 4 224 11.43 the electron and positive ion that are pro90Th : 2a  88Ra duced during an ionizing interaction between a molecule (or atom) and radiation 11.45 (a) yes (b) no (c) yes (d) no 11.47 It continues on, interacting with other atoms and forming more ion pairs. 11.49 Alpha is stopped; beta and gamma go through. 11.51 alpha, 0.1 the speed of light; beta, up to 0.9 the speed of light; gamma, the speed of light 11.53 (a) no detectable effects (b) nausea, fatigue, lowered blood cell count 11.55 to record the extent of their exposure to radiation 11.57 naturally occurring ionizing radiation 11.59 radon seepage, cosmic radiation, rocks and minerals, food and drink 11.61 so radiation can be detected externally 11.63 (a) tagged to white blood cells, which migrate to sites of infection thus locating the infection site (b) injected into the blood, used to locate blood flow blockages (c) injected into the blood, has affinity for healthy heart muscle tissue (d) tagged to red blood cells, used to determine blood volume based on concentration differences 11.65 They are usually a or b emitters. 11.67 (a) 4 (b) 4 (c) 2 (d) 3 11.69 neptunium-239 11.71 (a) 42a (b) 12H 11.73 (a) fusion (b) fusion (c) both (d) fission 11.75 (a) fusion (b) fission (c) neither (d) neither 11.77 Different isotopes of an element have the same chemical properties but different nuclear properties. 11.79 Temperature, pressure, and catalysts affect chemical reaction rates but do not affect nuclear reaction rates. 0 0 206 109 109 245 4 11.81 (a) 206 80Hg : 1b  81Tl (b) 46Pd : 1b  47Ag (c) 96 : 2a  249 241 4 245 11.82 (a) 54 hr (b) 90 hr (c) 108 hr 94Pu (d) 100 Fm : 2a  98Cf 254 4 242 1 246 12 (d) 126 hr 11.83 (a) 239 94Pu  2a : 96 Cm  0n (b) 96  6C : 102 No 4 1 30 23 2 21 4  4 10n (c) 27 13Al  2a : 0n  15P (d) 11Na  1H : 10Ne  2a

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A-6

Answers to Selected Exercises

0 1 143 11.84 142 11.85 12 elements 60Nd  0n : 61Pm  1b 11.86 4 neutrons 11.87 E  0 (negligible amount), F  0 (negligible amount), G  63 atoms, H  937 atoms 11.88 228Ac, 228Th, 224Ac 11.89 c 11.90 b 11.91 a 11.92 c 11.93 d 11.94 c 11.95 a 11.96 a 11.97 d 11.98 a

Chapter 12 12.1 (a) false (b) false (c) true (d) true 12.3 (a) meets (b) does not meet (c) does not meet (d) does not meet 12.5 Hydrocarbons contain C and H, and hydrocarbon derivatives contain at least one additional element besides C and H. 12.7 All bonds are single bonds in a saturated hydrocarbon, and at least one carbon–carbon multiple bond is present in an unsaturated hydrocarbon. 12.9 (a) saturated (b) unsaturated (c) unsaturated (d) unsaturated 12.11 (a) 18 (b) 4 (c) 13 (d) 22 12.13 (a) CH3O CH2 O CH2 O CH3 (b) CH3O CH2 O CHO CH2 O CH3 A CH3 (c) CH3O CH2 O CHO CH2 O CHO CH3 A A CH3 CH3 (d) CH3O CH2O CHO CH2 O CH3 A CH2 A CH3 12.15 (a) CH3O CHO CH2 O CH3 A CH3 (b) CH3O CHO CHO CHO CH2O CH3 A A A CH3 CH3 CH3 (c) CH3O CH2 O CH2O CH2 O CH2 O CH3 (d) CH3 A CH3O CO CH2O CH3 A CH3 12.17 (a) H H H H H A A A A A HO CO CO CO CO COH A A A A A H H H H H (b) H H H H H H H H A A A A A A A A HO CO CO CO CO CO CO CO COH A A A A A A A A H H H H H H H H (c) CH 3O 1CH 2 2 8OCH 3 (d) C6H14 12.19 the same molecular formula 12.21 (a) the same (b) different (c) different (d) different 12.23 a continuous chain of carbon atoms versus a continuous chain of carbon atoms to which one or more branches of carbon atoms are attached 12.25 (a) 2 (b) 5 (c) 18 (d) 75 12.27 one 12.29 (a) different compounds that are not constitutional isomers (b) different compounds that are constitutional isomers (c) different conformations of the same molecule (d) different compounds that are constitutional isomers 12.31 (b) CH3O CHO CH2O CHO CH3 (a) CH3O CH2O CHO CH2O CH3 A A A CH3 CH3 CH3

12.37 (a) 2,3,5-trimethylhexane (b) 2,2,4-trimethylpentane (c) 3-ethyl-3-methylpentane (d) 3-ethyl-3-methylhexane 12.39 horizontal chain, because it has more substituents (two) 12.41 (a) CH3O CH2O CHO CH O CH2O CH3 A A CH3 CH3 CH3 A (b) CH3O CH2O CO CH2O CH3 A CH2 A CH3 (c) CH3O CH2O CHO CH2O CH O CH2O CH2O CH3 A A CH2 CH2 A A CH3 CH3 (d) CH3 O CH2O CH2O CHO CH2O CH2O CH2O CH2O CH3 A CH2 A CH2 A CH3 12.43 (a) 2, 2 (b) 2, 2 (c) 2, 2 (d) 1, 1 12.45 (a) not based on longest carbon chain; 2,2-dimethylbutane (b) carbon chain numbered from wrong end; 2,2,3-trimethylbutane (c) carbon chain numbered from wrong end and alkyl groups not listed alphabetically; 3-ethyl-4-methylhexane (d) like alkyl groups listed separately; 2,4-dimethylhexane 12.47 (a) COCOCOCOCOCOCOC A C (b) COCOCOCOCOC A A C C (c) COCOCOCOC A C (d) COCOCOCOCOCOCOC A A C COC A C 12.49 (a) CH3OCHOCHOCHOCH3 A A A CH3 CH3 CH3 (b) CH3OCHOCHO CH2O CH3 A A CH3 CH2 A CH3 (c) CH3O CH2OCHOCHO CH2O CH2 OCH3 A A CH3 CH2 A CH3 (d) CH3O CH O CH2O CH2OCHOCH2O CH2 OCH3 A A CH3 CH2 A CH3 12.51 (a) constitutional isomers (b) same compound 12.53 (a) (b)

(c) CH3OCHO CH3 A CH3

(d) CH3O CH2OCHO CH2O CH3 A CH2 A CH3 12.33 (a) seven-carbon chain (b) eight-carbon chain (c) eightcarbon chain (d) seven-carbon chain 12.35 (a) 3-methylpentane (b) 2-methylhexane (c) 2-methylhexane (d) 2,4-dimethylhexane

(c)

(d)

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Answers to Selected Exercises

12.55 (a) 2-methyloctane (b) 2,3-dimethylhexane (c) 3-methylpentane (d) 5-isopropyl-2-methyloctane 12.57 (a) C8H18 (b) C9H20 (c) C10H22 (d) C11H24 12. 59 (a) 5, 1, 3, 0 (b) 5, 1, 1, 1 (c) 4, 3, 0, 1 (d) 4, 4, 0, 1 12.61 (a) isopropyl (b) isobutyl (c) isopropyl (d) sec-butyl 12.63 (a) CH3 O CH2 O CH2O CH2O CHO CH2O CH2O CH2O CH2O CH3 A CHO CH3 A CH2 A CH3 CH3 A CHO CH3 A (b) CH3O CH2O CH2O C O CH2O CH2O CH2O CH3 A CHO CH3 A CH3

(c) CH3O CHO CHO CH2O CHOCH2O CH2O CH2O CH3 A A A CH2 CH3 CH3 A CHO CH3 A CH3 (d) CH3O CH2O CH2OCHOCH2O CH2O CH2 OCH3 A CH3O C O CH3 A CH3 12.65 (a) 3 or 4 (b) 3 or 4 (c) none of them (d) 3 or 4 12.67 (a) (2-methylbutyl) group (b) (1,1-dimethylpropyl) group 12.69 (a) 16 (b) 6 (c) 5 (d) 15 12.71 (a) C6H12 (b) C6H12 (c) C4H8 (d) C7H14 12.73 (a) cyclohexane (b) 1,2-dimethylcyclobutane (c) methylcyclopropane (d) 1,2-dimethylcyclopentane 12.75 (a) must locate methyl groups with numbers (b) wrong numbering system for ring (c) no number needed (d) wrong numbering system for ring 12.77 (a)

(b)

(c)

(d)

12.79 (a) two (cyclobutane, methylcyclopropane) (b) three: dimethyl (1,1; 1,2); ethyl (c) one (methyl) (d) four: dimethyl (1,1; 1,2; 1,3); ethyl 12.81 (a) not possible CH3O CH2 H (b) CH3O CH2 CH2O CH3 H CH2O CH3

H H cis

(c) not possible

trans

(d)

CH3 A CH3 A A H A H cis

CH3 A H A A H A CH3 trans

12.83 50–90% methane, 1–10% ethane, up to 8% propane and butanes 12.85 boiling point 12.87 (a) octane (b) cyclopentane (c) pentane (d) cyclopentane 12.89 (a) different states (b) same state (c) same state (d) same state 12.91 (a) CO2 and H2O (b) CO2 and H2O (c) CO2 and H2O (d) CO2 and H2O 12.93 CH3Br, CH2Br2, CHBr3, CBr4 12.95 (a) CH3O CH2 A Cl

A-7

(b) CH2 O CH2O CH2 O CH3 CH3O CHO CH2O CH3 A A Cl Cl (c) (d) Cl Cl A CH2O CHO CH3 CH3O C O CH3 A A A Cl CH3 CH3 12.97 (a) iodomethane, methyl iodide (b) 1-chloropropane, propyl chloride (c) 2-fluorobutane, sec-butyl fluoride (d) chlorocyclobutane, cyclobutyl chloride (b) 12.99 (a) Cl F F A A A HO C O Cl FO C O COF A A A Cl Cl Cl Br (c) CH3O CHOBr (d) A A H A CH3 A H A Cl 12.101 (a) 14 (b) 5 (c) 4 (d) 19 12.102 (a) liquid (b) less dense (c) insoluble (d) flammable 12.103 (a) no (b) yes (c) no (d) no (b) Cl H CH3 12.104 (a) F H (c)

F (d) CH3

CH3 CH3

C

H

H

CH

CH2

I

CH3

Br

CH3 12.105 (a) C18H38 (b) C7H14 (c) C7H14F2 (d) C6H10Br2 12.106 (a) alkane (b) halogenated cycloalkane (c) halogenated alkane (d) cycloalkane 12.107 (a) 1 (b) (2-methyl, 3-methyl, 4-methyl) (c) 6 (2,2; 2,3; 2,4; 2,5; 3,3; 3,4) (d) 1 (3-ethyl) 12.108 (a) C O C O C O C O C O C O C C O C O C O C O C O C A heptane C 2-methylhexane

CO C O CO CO CO C A C 3-methylhexane

C O CO CO CO C A A C C 2,3-dimethylpentane

C A CO C O C O C O C A C 3,3-dimethylpentane

C A C O CO CO CO C A C 2,2-dimethylpentane

CO CO COCOC A A C C 2,4-dimethylpentane

CO C O C O C O C A C A C 3-ethylpentane

C A COCOCO C A A C C 2,2,3-trimethylbutane

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Answers to Selected Exercises

C C

(b)

C

C

C

13.19 (a) CH2 P CHO CHO CH2O CH3 A CH3 (c) CH2P CHO CH P CH2

(b) Cyclohexane Methylcyclopentane 1,1-Dimethyl 1,2-Dimethyl cyclobutane cyclobutane

C

C

C

C C

C

C

C C

C

1,2,3-Trimethyl Ethylcyclobutane 1,1,2-Trimethyl cyclopropane cyclopropane

1,3-Dimethyl cyclobutane

C C

C

C

C

C

C

CH2

(d) CH2PCHOCH2OI

1-Ethyl-2-methyl 1-Ethyl-1-methyl Propylcyclopropane cyclopropane cyclopropane

C

13.21 (a) 3-methyl-3-hexene (b) 2,3-dimethyl-2-hexene (c) 1,3-cyclopentadiene (d) 4,5-dimethylcyclohexene 13.23 (a) CH2PCH2 (b) (c) CH2PCHOBr

P

C

C

CH3

(d) CH2P CHO CHO CHP CH2 A CH2 A CH3

13.25 (a)

C

(b)

(c)

(d)

C Isopropylcyclopropane

(c) C O C O C O C O C A Cl

CO C O CO CO C A Cl

CO C O CO CO C A Cl

1-chloropentane

2-chloropentane

3-chloropentane

Cl A CO CO COC A C

C O CO CO C A A Cl C 1-chloro-2-methylbutane

2-chloro-2-methylbutane

C O CO CO C A A C Cl 1-chloro-3-methylbutane

Br A (d) CO C O C A Br 1,1-Dibromo propane

Br A CO C O C A Br 2,2-Dibromo propane

13.27 13.29 13.31 13.33

(a) 3-octene (b) 3-octene (c) 1,3-octadiene (d) 1,5-octadiene (a) positional (b) skeletal (c) skeletal (d) positional (a) 2 (b) 4 (c) 3 (d) zero C P C O C O CO C O C C O C P C O CO C O C 1-Hexene

2-Hexene

C O C O C P CO C O C C P C O CO C O C C P C O CO CO C A A 3-Hexene C C

C O CO CO C A A C Cl

2-Methyl-1-pentene

C P C O CO C O C A C

2-chloro-3-methylbutane

C A C O C O C OCl A C

3-Methyl-1-pentene

C OC P CO C O C C O C P CO C O C A A C C

4-Methyl-1-pentene

2-Methyl-2-pentene

3-Methyl-2-pentene

C O C P CO C O C A C

C P C O CO C A A C C

4-Methyl-2-pentene

2,3-Dimethyl-1-butene

C A C P C O CO C A C

1-chloro-2,2-dimethylpropane

3,3-Dimethyl-1-butene

CO C O C A A Br Br

CO C O C A A Br Br

1,2-Dibromo propane

1,3-Dibromo propane

12.109 (a) 1,2-diethylcyclohexane (b) 3-methylhexane (c) 2,3-dimethyl4-propylnonane (d) 1-isopropyl-3,5-dipropylcyclohexane 12.110 (a) one (b) two (c) four (d) eight 12.111 c 12.112 a 12.113 b 12.114 b 12.115 d 12.116 c 12.117 c 12.118 c 12.119 b 12.120 c

C O C P CO C A A C C 2,3-Dimethyl-2-butene

2-Ethyl-1-butene

13.35 (a) no (b) no (c) CH3O CH2

CH2O CH3 CH3O CH2 H G G D D CP C CP C D D G G H CH2 O CH3 H H

Chapter 13 13.1 one or more carbon–carbon multiple bonds are present 13.3 carbon–carbon double bond 13.5 they are very similar 13.7 (a) unsaturated, alkene with one double bond (b) unsaturated, alkene with one double bond (c) unsaturated, diene (d) unsaturated, triene 13.9 (a) C4H10 (b) C5H10 (c) C5H8 (d) C7H10 13.11 (a) CnH2n2 (b) CnH2n2 (c) CnH2n2 (d) CnH2n6 13.13 (a) alkene with one double bond (b) alkene with one double bond (c) diene (d) triene 13.15 (a) 2-butene (b) 2,4-dimethyl-2-pentene (c) 3-methylcyclohexane (d) 1,3-cyclopentadiene 13.17 (a) 2-pentene (b) 2,3,3-trimethyl1-butene (c) 2-methyl-1,4-pentadiene (d) 1,3,5-hexatriene

C P C O CO C A C A C

cis

(d)

CH3 A CH O CH3

CH3

D G CP C D G H H cis

trans

CH3

H G D CPC D G H CHO CH3 A CH3 trans

13.37 (a) cis-2-pentene (b) trans-1-bromo-2-iodoethene (c) tetrafluoroethene (d) 2-methyl-2-butene

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Answers to Selected Exercises

13.39 (a) CH3O CH2

H G D CP C D G CH3 CH2 O CH3

13.67 C nH 2n26 13.69 (a) 1-hexyne (b) 4-methyl-2-pentyne (c) 2,2-dimethyl-3-heptyne (d) 1-butyne 13.71 C C C C C (1-pentyne) C C

CH2 O CH3 G D CP C D G H H

(b) CH3

(c) CH3

H G D CPC D G H CH2 O CH O CH2O CH3 A CH3

(d) CH2 P CH

H D G CP C D G CH3 H

13.41 a compound used by insects (and some animals) to transmit messages to other members of the same species 13.43 Isoprene, the building block for terpenes, contains 5 carbon atoms. 13.45 (a) gas (b) liquid (c) liquid (d) liquid 13.47 (a) yes (b) no (c) yes (d) no CH2 O CH2 13.49 (a) CH2 P CH2  Cl2 A A Cl Cl CH3O CH2 A Cl

(b) CH2 P CH2  HCl (c) CH2 P CH2  H2

Ni

CH3O CH3

CH3 O CH2 A Br CH2O CHO CH3 13.51 (a) CH2 P CHO CH3  Cl2 A A Cl Cl (b) CH2 P CHO CH3  HCl CH3OCHOCH3 A Cl

(d) CH2 P CH2  HBr

(c) CH2 P CHO CH3  H2

Ni

(d) CH2 P CH O CH3  HBr

CH3OCH2OCH3 CH3OCH O CH3 A Br

13.53 (a) CH3OCH O CHO CH3 A A Cl Cl (b) CH3OCH2O CHO CH3 (c) A Cl

A-9

C C

C C

C C (2-pentyne) C (3-methyl-1-butyne)

C 13.73 because of the linearity (180 angles) about an alkyne’s carbon– carbon triple bond 13.75 Their physical properties are very similar. 13.77 (a) CH3O CH3 (b) Br Br Br (c) A A A CH3OC O CH CH3OC O CH3 A A A Br Br Br (d) CH2P CH A Cl 13.79

13.81 implies that there are two types of carbon–carbon bonds present which is not the case 13.83 (a) 1,3-dibromobenzene (b) 1-chloro-2fluorobenzene (c) 1-chloro-4-fluorobenzene (d) 3-chlorotoluene 13.85 (a) m-dibromobenzene (b) o-chlorofluorobenzene (c) p-chlorofluorobenzene (d) m-chlorotoluene 13.87 (a) 2,4-dibromo1-chlorobenzene (b) 3-bromo-5-chlorotoluene (c) 1-bromo-3-chloro2-fluorobenzene (d) 1,4-dibromo-2,5-dichlorobenzene 13.89 (a) 2-phenylbutane (b) 3-phenyl-1-butene (c) 3-methyl-1phenylbutane (d) 2,4-diphenylpentane (b) CH3 (c) CH3 13.91 (a) CH2O CH3 CH3 CH2O CH3 CH2O CH3 (d)

13.93 liquid state 13.95 petroleum 13.97 (a) substitution (b) addition (c) substitution (d) addition 13.99 (a) Br2 (b) (c) CH3 CH2 Br CH3 A CHO CH3

(d) HO

13.55 (a) Br2 (b) H2  Ni catalyst (c) HCl (d) H2O  H2SO4 catalyst 13.57 (a) 2 (b) 2 (c) 2 (d) 3 13.59 a large molecule formed by the repetitive bonding together of many smaller molecules 13.61 a polymer in which the monomers add together to give the polymer as the only product 13.63 (a) CF 2 “ CF 2 (b) CH2P CO CHPCH2 (c) CH2 P CH (d) CH2 P CH A A Cl Cl

13.101 carbon atoms are shared between rings 13.103 (a) C2H4 (b) C3H4 (c) C2H2 (d) CH4 13.104 (a) more (b) more (c) more (d) the same number 13.105 (a) no (b) yes (c) no (d) yes 13.106 (a) All have six carbon atoms. (b) Cyclohexane has 12 H atoms, cyclohexene 10, and benzene 6. (c) Cyclohexane and benzene undergo substitution; cyclohexene undergoes addition. (d) All are liquids. 13.107 (a) CH3 C C CH2 CH CH3 (b) CH2

CH

CH

CH3

13.65 (a)

Cl (c) CH2

CH

CH2

CH2

(b)

(d) CH2

CH

CH

CH2O CH2OCH2O CH2OCH2O CH2 CH2O CHO CH2O CHOCH2O CH A A A Cl Cl Cl

(c)

CHO CHOCHO CHOCHO CH A A A A A A Cl Cl Cl Cl Cl Cl

(d)

CH2O CHO CH2O CHO CH2O CH A A A Cl Cl Cl

CH

CH3

CH2

CH

CH2

CH3 13.108 (a) two (b) one (c) two (d) two 13.109 (a) CH2 CH

CH2

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A-10

Answers to Selected Exercises

(b) CH2

CH

CH2

Cl (c) CH3

(d) CH3

CH2

CH2

C

C

CH2

CH2

CH2

CH2

C

CH3

13.110 It would require a carbon atom that formed five bonds. 13.111 The substituted carbon atoms in 1,2-dichlorobenzene have only one substituent. 13.112 CH2 CH CH2 CH2 CH3 CH3 CH CH CH2 CH3 CH2

C

CH3

CH2

CH

CH3 CH3

CH3

CH3

A

OH

1,3-Butanediol

(c) CH3 O CHO CHO CH3 A

(d)

A

OH

CH3 OH HO

CH2

CH3 13.113 1,2,3-trimethylbenzene; 1,2,4-trimethylbenzene; 1,3,5trimethylbenzene; 2-ethyltoluene; 3-ethyltoluene; 4-ethyltoluene; propylbenzene; isopropylbenzene 13.114 (a) 3 (b) 3 (c) 11 (d) 3 13.115 c 13.116 d 13.117 b 13.118 a 13.119 b 13.120 a 13.121 b 13.122 c 13.123 c 13.124 a

Chapter 14 14.1 (a) 2 (b) 1 (c) 4 (d) 1 14.3 R—OH 14.5 R—O—H versus H—O—H 14.7 (a) 2-pentanol (b) 3-methyl-2-butanol (c) 2-ethyl-1-pentanol (d) 2-butanol 14.9 (a) 1-hexanol (b) 3-hexanol (c) 5,6-dimethyl-2-heptanol (d) 2-methyl-3-pentanol 14.11 (a) CH2O CHO CH3 (b) CH3 O CH O CH2 O CHO CH3 (c)

A

A

OH

1,3-Cyclopentanediol

(cis–trans forms)

A

CH2

2-Methyl-1-butanol

CH3

CH3

CH3

OH

OH

3-Methyl-2-butanol

CH3 CH3

A

CH3 CH

C

CH

A

CH3

(cis–trans forms)

CH2

(b) CH3O CH O CH2 O CH2

14.21 (a) CH2 O CHO CH3

CH

CH3

14.23 (a) no (b) yes (c) yes (d) yes 14.25 1-heptanol, 2-heptanol, 3-heptanol, 4-heptanol 14.27 x  1, 2, 3 14.29 (a) ethanol with all traces of H2O removed (b) ethanol (c) 70% solution of isopropyl alcohol (d) ethanol 14.31 (a) 1,2,3-propanetriol (b) ethanol (c) methanol (d) methanol 14.33 Alcohol molecules can hydrogen-bond to each other; alkane molecules cannot. 14.35 (a) 1-heptanol (b) 1-propanol (c) 1,2-ethanediol 14.37 (a) 1-butanol (b) 1-pentanol (c) 1,2-butanediol 14.39 (a) 3 (b) 3 (c) 3 (d) 3 14.41 (a) CH2 O CH3 (b) CH3O CH2O CH2 A

A

OH (d) CH3 O CH2 O CHO CH2 O CH3

OH (c)

OH A

A

CH3 O CH2 O CO CH3

OH

A

CH3 14.43 (a) 2 (b) 2 (c) 1 (d) 2 14.45 (a) CH2P CHO CH3 (b) CH3O CH2O C P CH2 A

CH3 (c) CH3O CHP CH2

A

A

A

(d) CH3 O CH2O CH2 O O O CH2O CH2 O CH3

CH3

OH

CH3

14.47 (a) CH3 O CHO CHO CH3 (b) CH3 O CH2O CH2 or CH3 O CHO CH3

(d)

OH A

OH

A

CH3 O CO CH3

A

OH CH3 (c) CH3 OCH2 O OH

CH3

A

A

OH

OH

(d) CH3 O CHO CH2O OH A

CH3 14.49 (a) CH3 O CH2O CHO CH3 (b) CH3 O CH2 OCH2

14.13 (a) CH2 O CH2 O CH2 O CH2 O CH3 A

OH (c) CH3 O CH2O CH2

1-Pentanol

A

(b) CH2 O CH2 O CH3 (c) CH3 O CHO CH2 O OH A OH

A

(c)

CH3

(b)

CH3

O B

(d) CH3 O CH2O O O CH2O CH3

CH3O CO CH2O CH3

2-Butanol

14.15 (a) 1,2-propanediol (b) 1,4-pentanediol (c) 1,3-pentanediol (d) 3-methyl-1,2,4-butanetriol 14.17 (a) cyclohexanol (b) trans-3-chlorocyclohexanol (c) cis-2-methylcyclohexanol (d) 1-methylcyclobutanol 14.19 (a) CH3O CHO CH2O CHP CH2 A

OH (b) CHq CO CHO CH2 O CH3 A

CH3

D G CP C D G

H

14.53 white solid, water soluble, hydrocarbon insoluble, does not absorb oxygen 14.55 Phenols require the —OH groups to be attached directly to the benzene ring. 14.57 (a) 3-ethylphenol (b) 2-chlorophenol (c) o-cresol (d) hydroquinone 14.59 (a) OH (b) OH CH2O CH3 Br

(c) CH3 O CHO CP CH2 A

A

OH CH3

OH

H

CH2 O OH

(d)

2-Methyl-1-Propanol

(d) CH3O CH2O CHO OH

(d) HO O CH2

A

OH

OH 14.51 (a) CH3 O CH2O CH2O Cl

A

CH3 1-Propanol

A

OH

Br

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Answers to Selected Exercises

(c)

OH

1-propene; allyl methyl sulfide 14.109 (a) 2-hexanol (b) 3-phenyoxy-1propene (c) 2-methyl-2-propanol (d) ethoxyethane 14.110 CH3 CH2 O CH2 O CH2 O CH2 O CH3

OH

(d)

A

OH

CH3

OH

14.61 low-melting solids or oily liquids 14.63 (a) both are flammable (b) both undergo halogenation 14.65 O OH

CH2 O CHO CH2 O CH3

14.67 An antiseptic kills microorganisms on living tissue; a disinfectant kills microorganisms on inanimate objects. 14.69 BHA has methoxy and tert-butyl groups; BHT has a methyl group and two tert-butyl groups. 14.71 (a) yes (b) no (c) yes (d) yes 14.73 (a) 1-ethoxypropane (b) 2-methoxypropane (c) methoxybenzene (d) cyclohexoxycyclohexane 14.75 (a) ethyl propyl ether (b) isopropyl methyl ether (c) methyl phenyl ether (d) dicyclohexyl ether 14.77 (a) 1-methoxypentane (b) 1-ethoxy-2-methylpropane (c) 2-ethoxybutane (d) 2-methoxybutane 14.79 (a) CH3 O CHO OO CH2O CH2 O CH3 A

(b) CH3 O CH2 O O

O

CH3

A

A

OH

CH3

CH2

CH3

A

OH

CH2 O CH2 O CH O CH3 A

A

OH

CH3

CH3 CH3

C

CH2

CH3 OH

CH3 O CH2 O CH O CH2 O CH3 A

OH CH3 O CH2 O CH2 O CH2 O O O CH3

CH3 O CH O CH O CH3 A

A

OH CH3 CH3 O CH O CH2 O O O CH3 A

CH3 CH3

A

CH3

OO CH2 O CH3

(d)

C

CH3 O CHO CH2 O CH2 O CH3

CH3 O CH2 O CH O O O CH3

CH3 (c)

CH3

OH

 H3O

 H2O

A-11

CH3

C

O

CH3

CH3 CH3 O CH2 O CH2 O O O CH2 O CH3

CH3

14.81 (a) no (b) no (c) yes (d) no 14.83 butyl methyl ether, sec-butyl methyl ether, isobutyl methyl ether, tert-butyl methyl ether, ethyl isopropyl ether 14.85 (a) CH3O O O CH2OCH2O CH3, CH3O O O CHOCH3, A CH3 CH3O CH2 OOO CH2O CH3

(b) CH3O CH2OCH2O CH2O OH, CH3O CH2OCHO OH, A CH3

14.87 x  1, 2, and 3 14.89 Dimethyl ether molecules cannot hydrogenbond to each other; ethanol molecules can. 14.91 flammability and peroxide formation 14.93 No oxygen–hydrogen bonds are present. 14.95 (a) noncyclic ether (b) noncyclic ether (c) cyclic ether (d) nonether 14.97 R—S—H versus R—O—H 14.99 (a) CH3 O CH2 O CH2 O CH2 (b) CH3 O CH2 O CHO CH2 O CH2 A

(c)

SH

A

A

CH3

SH

(d) CH2 O CH2 A

A

SH

SH

A

CH3

CH3 14.111 1-pentanol 14.112 CH3—O—CH3, CH3—CH2—CH2 —O—CH2 —CH2 —CH3, and CH3—O—CH2—CH2—CH3 14.113 (a) disulfide (b) peroxide (c) alcohol, thiol, thioalcohol (d) ether, sulfide, thioether 14.114 (a) 3-methoxy-1-propanol (b) 1,2-dimethoxyethane (c) methylthioethane (d) 1-ethylthio-2-methoxyethane 14.115 d 14.116 c 14.117 b 14.118 c 14.119 b 14.120 a 14.121 a 14.122 d 14.123 a 14.124 d 15.1 (a) yes (b) no (c) yes (d) yes 15.3 similarity: both have bonds involving four shared electrons; difference: C“O is polar, C“C is not polar 15.5 120 15.7 (a) yes (b) yes (c) no (d) yes 15.9 (a) aldehyde (b) ketone (c) amide (d) carboxylic acid 15.11 (a) neither (b) ketone (c) neither (d) aldehyde O O O O 15.13 B B B B HO COH, CH3 O COH, CH3 OCO CH3, CH3 OCH2 OCO CH3

Chapter 15

CH3 A CH3O CH O CH2 OOH, CH3O COOH A A CH3 CH3

SH

CH3 O CH O O O CH2

14.101 (a) methyl mercaptan (b) propyl mercaptan (c) sec-butyl mercaptan (d) isobutyl mercaptan 14.103 Alcohol oxidation produces aldehydes and ketones; thioalcohol oxidation produces disulfides. 14.105 R—S—R versus R—O—R 14.107 (a) methylthioethane; ethyl methyl sulfide (b) 2-methylthiopropane; isopropyl methyl sulfide (c) methylthiocyclohexane; cyclohexyl methyl sulfide (d) 3-(methylthio)-

15.15 (a) aldehyde (b) neither (c) ketone (d) ketone 15.17 (a) 2-methylbutanal (b) 4-methylheptanal (c) 3-phenylpropanal (d) propanal 15.19 (a) pentanal (b) 3-methylbutanal (c) 3-methylpentanal (d) 2-ethyl-3-methylpentanal 15.21 (a) O CH3 B A CH3OCH2O CHOCH2O COH (b)

O B CH3OCH2O CH2O CH2O CHO COH A CH2 A CH3

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A-12 (c)

Answers to Selected Exercises 15.59 (a)

Cl O A B CH3 OCO COH A Cl

(c)

(d)

CH3 O OH A A B CH3 OCH2 OCH2 OCH2 O CHOCH2 OCHO COH (b) 15.23 (a) O O B B O CH O COH CH HOC OH 3 2 (d) O O (c) B B COH COH Cl

CH3

CH3

15.25 (a) propionaldehyde (b) propionaldehyde (c) dichloroacetaldehyde (d) o-chlorobenzaldehyde 15.27 (a) 2-butanone (b) 2,4,5-trimethyl-3hexanone (c) 6-methyl-3-heptanone (d) 1,1-dichloro-2-butanone 15.29 (a) 2-hexanone (b) 5-methyl-3-hexanone (c) 2-pentanone (d) 4-ethyl3-methyl-2-hexanone 15.31 (a) cyclohexanone (b) 3-methylcyclohexanone (c) 2-methylcyclohexanone (d) 3-chlorocyclopentanone 15.33 (b) O (a) O CH3 B B A CH3 OCO CHOCH2O CH3 CH3 OCH2O COCH2O CH2O CH3 (c)

15.35 (a) (c)

O (d) Cl B A CH2 OCO CH3

O

CH3 O B A CH3 OCHOCO CH2O CH2OCH3

O B CH3 OC

(d)

O B CH3 OCOOH

O B HO COOH

(d)

(b)

O B CH3 OCH2 OCH2 OCH2 OCOOH

Cl Cl O B A A CH3 OCH2OCHOCHO CH2 OCOOH

15.61 appearance of a silver mirror 15.63 Cu2⫹ ion 15.65 (a) no (b) yes (c) yes (d) no 15.67 (a) CH3O CH2O CH2 OCH2 (b) CH3 OCH2O CHOCH2 OCH3 A A OH OH (c) CH3 OCHOCH2 OCH2 A A CH3 OH

(d) CH3O CHOCHOCH2 OCH2 OCH3 A A CH3 OH

15.69 R—O— and H— 15.71 (a) no (b) yes (c) yes (d) no 15.73 (a) CH3O CHOOOCH2 O CH3 (b) OH A A COCH2 OCH2 OCH3 CH O OH 3 A OOCH3 (c)

OH A CH3 OCH2 OCH2 OCH A OO CH2 OCH3

(d)

OH A CH3 OCO CH3 A OO CHOCH3 A CH3 O B CH3O CH2 OCOH

15.75 O (b) Cl B A CH2 OCO CH3

O B CH3 OC

15.37 (a) heptanal (b) 2-heptanone, 3-heptanone, 4-heptanone 15.39 (a) 1 aldehyde, no ketones (b) 1 aldehyde, 1 ketone 15.41 x ⫽ 2, 4, 5 O O O B B B 15.43 COCOCOCOCOH, COCOCOCOH, COCOCOCOH, A A C C O C O O O B B B A B COCOCOH, COCOCOCOC, COCOCOC, COCOCOCOC A A C C 15.45 formaldehyde is an irritating gas at room temperature; formalin is an aqueous solution containing 37% formaldehyde by mass 15.47 a colorless, volatile liquid that is miscible with both water and nonpolar solvents; its main use is as a solvent 15.49 Dipole–dipole attractions between molecules raise the boiling point. 15.51 2 15.53 ethanal, because it has a shorter carbon chain O O (b) 15.55 (a) B B CH3O CH2 OCH2 OCH2 OCOH CH3OCH2O COCH3 (d) (c) CH3 O A B CH3 O CH3O COCH2 OC OH A CH3 15.57 (a) CH3 OCH2O CHOCH2 OCH3 (b) CH3 OCH2OOH A OH (c) CH3OCHOCH3 (d) CH3 OCH2O CH2O CH2O CHOCH2 A A A CH3 OCH2 OH OH

(a)

OH A CH3 OCH2 OCH2 OCH A OO CH2 OCH3

(b)

(c)

OH A CH3 OCH2 OCO CH3 A OO CH3

(d)

CH2OH O OH OH

15.77 (a) yes (b) yes (c) no (d) yes 15.79 (a) CH3 O OH (b) CH3 OCHOOO CH3 A OH (c) CH3O CH2 OCHOOO CH3 (d) CH3 OCHOOO CH3, CH3 O OH A A OH OO CHO CH3 A CH3 15.81 (a)

O 2 CH3 O OH B CH3 O COH,

(c) (d)

(b)

O 2 CH3 O OH B CH3OCO CH3 ,

O B CH3 O CH2O COCH2 OCH3 , CH3 O OH, CH3 O CH2O OH

O B CH3 O CH2 OCH2 O CH2 OC OH , 2 CH3 O OH 15.83 (a) dimethyl acetal of ethanal (b) dimethyl acetal of propanone (c) ethyl methyl acetal of 3-pentanone (d) dimethyl acetal of pentanal 15.85 monomers are connected in a three-dimensional cross-linked network 15.87 mono-, di-, and tri-substituted phenols 15.89 thiocarbonyl compound

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Answers to Selected Exercises

15.91

16.15 (a)

S S B B (a) HO CO H (b) HO CO H

O B CH3 OCH2 OCH2 OCH2 O COOH

S S B B (c) CH3 O CO CH3 (d) CH3 O CO CH3

(b)

O B CH3 O COOH

15.93 (a) By definition, the carbonyl carbon atom is number 1 in an aldehyde; therefore, the number does not have to be specified in the name. (b) There is only one possible location for the carbonyl group in propanone; therefore, its location does not have to be specified. 15.94 (a) A ketone carbonyl group cannot be on a terminal carbon atom. (b) It requires a carbon atom with five bonds. (c) It requires a carbon atom with five bonds. (d) It requires a carbon atom with five bonds. 15.95 (a) a carbon atom bonded to both a hydroxyl group and an alkoxy group (b) a carbon atom bonded to two alkoxy groups 15.96 (a) OH OO CH2O CH3 A A CH3O CH2OCHOOOCH2O CH3 CH3O CH2OCHOOO CH2 O CH3 (b) OH OO CH3

(d)

Br O B A CH3 OCH2 O CH2 O CHOCH2 OCOOH

15.97

OO CH3 O OH CH CH2

15.98 (a) ketone, alkene (b) aldehyde, alcohol, ether (c) ketone, alkyne (d) aldehyde, ketone 15.99 (a) ketone (b) aldehyde (c) aldehyde (d) aldehyde 15.100 c 15.101 c 15.102 c 15.103 b 15.104 d 15.105 b 15.106 c 15.107 c 15.108 d 15.109 b 16.3 (a) carboxylic acid (b) carboxylic acid derivative (c) neither (d) carboxylic acid 16.5 (a) butanoic acid (b) 4-bromopentanoic acid (c) 3-methylpentanoic acid (d) chloroethanoic acid 16.7 (a) hexanoic acid (b) 3-methylpentanoic acid (c) 2,3-dimethylbutanoic acid (d) 4,5-dimethylhexanoic acid 16.9 O (a) B CH3 O CH2 O CHOCOOH A CH3 O CH2 (b)

CH3 CH3 O B A A CH3 OCHO CH2 O CH2 OCHOCOOH

(c)

CH3 O B A CH3 OCHO COOH

(d)

Cl O A B ClO CHO COOH

16.11 (a) propanedioic acid (b) 3-methylpentanedioic acid (c) 2-chlorobenzoic acid (d) 2-bromo-4-chlorobenzoic acid 16.13 CH3 O O (a) (b) O CH3 B A B B A CH3 O CH2 O COOCOOH HOOCO COCH2 OCOOH A A CH3 CH3 O CH3 O B A B HOOCO COCH2 OCH2 O COOH A CH3

(d)

COOH Cl

Cl

Cl O B A CH3 OCH2 O CHOCOOH

O O B B HOO COCH2 OCOOH

(b)

O O B B HOOC OCH2 O CH2 O COOH

(c)

Br O O B B A HOOCO CH2 OCH2 OCHOCH2 O CH2 O COOH

(d)

O CH3 O B A B HOOCO CHO CH2 OCH2 O COOH

16.19 (a) 3 (b) 1 (c) 2 (d) 1 16.21 (a) carbon–carbon double bond (b) hydroxyl group (c) carbon–carbon double bond (d) hydroxyl group 16.23 (a) propenoic acid (b) 2-hydroxypropanoic acid (c) cisbutenedioic acid (d) 2-hydroxyethanoic acid 16.25 O O (a) B B CH3 O CH2 OCO CH2 O COOH (b)

Chapter 16 16.1 (a) yes (b) no (c) no (d) yes

(c)

16.17 (a)

OO CH3

CH2 CH2

(c)

A-13

OH O A B CH3 O CH2 O CHOCOOH

(c) CH3

(d)

G CHPCH

O B G CH2 OCH2 O COOH

O OH OH O B A B A HOOCO CHOCHOCH2 O COOH

16.27 (a) propionic acid (b) propionic acid (c) succinic acid (d) glutaric acid 16.29 (a) hydroxy, carboxy (b) hydroxy, carboxy (c) keto, carboxy (d) hydroxy, carboxy 16.31 (a) 2 (b) 5 16.33 (a) solid (b) solid (c) liquid (d) solid 16.35 O O (a) (b) B B CH3 O COOH CH3 O COOH (c)

CH3 (d) O B A CH3 OCH2 OCHO CH2 O COOH

O B COOH

16.37 (a) 1 (b) 3 (c) 2 (d) 2 16.39 (a) 1 (b) 3 (c) 2 (d) 2 16.41 (a) pentanoate ion (b) citrate ion (c) succinate ion (d) oxalate ion

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A-14

Answers to Selected Exercises

16.43 (a)

O B CH3 OCOOH  H2O

(b)

O B  H3O  CH3 O COO

O O OH B B A HOO COCH2 OCO CH2 O COOH  3H2O A COOH B O O OH O B B A   3H3O  OO CO CH2 OCO CH2 O COO A COO B O

(c)

O B CH3 OCOOH  H2O

(d)

O B CH3 OCH2 O CHO CO OH  H2O A CH3

O B H3O  CH3 O COO

O B  H3O  CH3OCH2 O CHO CO O A CH3 16.45 (a) potassium ethanoate (b) calcium propanoate (c) potassium butanedioate (d) sodium pentanoate 16.47 O O (a) B B CH3 O COOH  KOH CH3 O COO K  H2O (b)

O B 2 CH3 OCH2 OCOOH  Ca(OH)2

冢

冣

O B CH3OCH2 OCOO 2 Ca2  2H2O

(c)

O O B B HOO COCH2 OCH2OCOOH  2KOH O O B B   K OOCOCH2 OCH2 OCOO K  2H2O

(d)

O B CH3 OCH2 OCH2OCH2OCOOH  NaOH O B CH3O CH2O CH2OCH2OCOO Na  H2O

16.49 (a)

O B CH3 OCH2 OCH2OCOO Na  HCl O B CH3 OCH2 OCH2 OCOOH  NaCl

(b)

O O B B OOCOCOO K  2HCl

 

K

O O B B HOOCOCOOH  2KCl (c)

冢



冣

O O B B OOCOCH2 OCOO 2 Ca2  2HCl O O B B HOOCO CH2O COOH  CaCl2

(d)

O B COO Na

O B COOH  HCl

 NaCl

16.51 a compound used as a food preservative 16.53 (a) benzoic acid (b) sorbic acid (c) sorbic acid (d) propionic acid 16.55 (a) two oxygen atoms (b) two carbon atoms 16.57 (a) yes (b) yes (c) no (d) yes 16.59 O (a) B CH3 OCH2 OCOOO CH3 (b)

O B CH3 OCOOOCH2 O CH2OCH3

(c)

CH3 O CH3 B A A CH3OCH2O CHOCOOO CHOCH3

(d)

CH3 O A B CH3O CH2O CH2 OCH2 OCOOOCHO CH2OCH3

16.61 (a)

O B CH3OCH2 OCOOH; CH3 ¬ CH2 ¬OH

(b)

O B CH3OCH2 OCH2 OCOOH; CH 3 ¬ OH

(c)

O B CH3O COOH;

OH (d)

O B COOH; CH3 ¬ OH

16.63 a cyclic ester; intermolecular esterification of a hydroxyacid 16.65 (a) methyl propanoate (b) methyl methanoate (c) propyl ethanoate (d) isopropyl propanoate 16.67 (a) methyl propionate (b) methyl formate (c) propyl acetate (d) isopropyl propionate 16.69 (a) ethyl butanoate (b) propyl pentanoate (c) methyl 3-methylpropanoate (d) ethyl propanoate 16.71 (a) O (b) O B B HO COOO CH3 CH2 OCOOOCH2 OCH3 (c)

(d) Br CH3 O O B B A A CH3 OCO O O CH2O CHO CH3 CH3 OCOOOCHO CH3

16.73 (a) ethyl ethanoate (b) methyl ethanoate (c) ethyl butanoate (d) 1-methylpropyl hexanoate 16.75 acid part is the same; alcohol part is methyl (apple) versus ethyl (pineapple) 16.77 the —OH group of salicylic acid has been esterified (methyl ester) in aspirin 16.79 pentanoic acid, 2-methylbutanoic acid, 3-methylbutanoic acid, 2,2-dimethylpropanoic acid 16.81 methyl pentanoate, methyl 2-methylbutanoate, methyl 3-methylbutanoate methyl 2,2-dimethylpropanoate 16.83 nine (methyl butanoate, methyl 2-methylpropanoate, ethyl propanoate, propyl ethanoate, isopropyl ethanoate, butyl methanoate, sec-butyl methanoate, isobutyl methanoate, tert-butyl methanoate) 16.85 O O O B B B CH3O CH2OCO OH, CH3O C O O OCH3, H O C O O OCH2 O CH3 16.87 No oxygen–hydrogen bonds are present. 16.89 There is no hydrogen bonding between ester molecules.

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Answers to Selected Exercises

16.91 (a)

16.99 (a)

O B CH3OCH2 OCOOH; CH3 ¬ CH2 ¬ OH

CH3 O B A CH3 OCHO COOH;

(c)

O B CH3OCH2 OCH2 OCOOH; CH3 ¬ OH

O (b) same as part a. B CH3 OCO S OCH3

OH

(c)

16.101 acetic acid and coenzyme A O O O O 16.103 B B B B OCO COO O(CH2 )3 OO OCO COO O(CH2 )3 OO O 16.105

O CH3 B A COOH; CH3OCHOOH

(d)

16.93 (a)

O B CH3 OCH2O COO Na; CH3 ¬ CH2 ¬OH

(b)

(c)

CH3 O B A CH3O CHOCOO Na ;

CH3 O A B COO Na; CH3 OCHOOH

O O B B CH3O CH2OCH2O C O O O C O CH2O CH2O CH3

16.113 (a) ethanoic propanoic anhydride (b) pentanoyl chloride (c) 2,3-dimethylbutanoyl chloride (d) methanoic propanoic anhydride 16.115 (a) O B CH3O CH2OCH2O CH2OCO OH

(b)

CH3 O A B CH3 OCHO COO Na; CH3 ¬CH2 ¬ OH

(c)

O B HOCOOH; CH3 ¬CH2 ¬CH2 ¬ CH2 ¬OH

(d)

O CH3 CH3 A A B   CH3OCOO Na ; CH3 OCHO CHOCH2 OOH

16.97 (a)

O B CH3 OCO S OCH2 OCH3

O B HO CO S O CH2O CH2OCH3

(c)

O O B B CH3O CO OH, CH3O CO O O CH2OCH3

(b)

(d)

16.107 ethylene glycol and terephthalic acid 16.109 specialty packaging, orthopedic devices, and controlled drug-release formulations 16.111 (a) O O B B (b) CH3O CH2OCOCl CH3O CHO CH2OCOCl

16.117 (a)

CH3 O A B CH3OCHOCOOH; CH3 ¬ CH2 ¬ OH

O (c) B CH3O (CH2 )8 OCO SOCH3

HO¬CH2¬CH2¬CH2¬OH

O B (b) CH3O CH2OCH2O CH2OCO OH

16.95 (a)

(b)

O O B B HOO COCH2OCH2O COOH;

O O B B (d) CH3O CH2OCH2O C O O O C O CH3

OH

O B CH3 OCH2 OCH2OCOO Na; CH3 ¬OH

(d)

O (d) same as part c. B H OCO S OCH2 OCH3

O B CO SO CHOCH3 A CH3

O O B B CH3O C O OH, CH3O C O O O CH2O CH2O CH2O CH3

16.119 (a) propanoyl group (b) butanoyl group (c) butanoyl group (d) ethanoyl group 16.121 an ester and HCl 16.123 (a) (b) O O B B HOO P OOO CH3 HOO P OOO CH3 A A OH OOCH3 O O O (c) (d) B B B OONOOO CH3 OONOOO CH2 OCH2 O O ONOO 16.125 H3PO4 is a triprotic acid, and H2SO4 is a diprotic acid. 16.127 (a) 2,2 (b) 7,1 (c) 7,1 (d) 6,3 16.128 O O O O B B B B HO O C O CH2 O COOH HO O C O CH CH O COOH B

(b)

A-15

Malonic acid

O OH O B A B HO O C O CH O CH2 O COOH Malic acid

Maleic acid (cis isomer)

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A-16

Answers to Selected Exercises

16.129 CnH2n2O2 16.130 (a) ethyl 2-methylpropanoate (b) 2-methylbutanoic acid (c) ethyl thiobutanoate (d) sodium propanoate O 16.131 B CH3O COOO CH2 O CH3

17.35 (a) CH3 ¬ CH2 ¬ NH3 (b) OH (c) CH3 OCHONHOCH3 A CH3

16.132 (a)

(d) CH3 ¬ CH2 ¬ NH2 ¬ CH2 ¬ CH3; OH



O B CH3O CH2 O COO Na; CH3O OH O O (c) B B CH3O CH2 O CO SO CH3 CH3 O COO Na

(d)

OH O B A HO O C O CH2 O CH2 O CH OCH2 OCH2

(b) CH3 OCH2 ONO CH2 OCH3 A CH2 O CH3 (c) CH3 OCH2 ONO CH2 OCH3

O

(b)

17.37 (a) dimethylammonium ion (b) triethylammonium ion (c) N,N-diethylanilinium ion (d) N-isopropylanilinium ion 17.39 (a) CH3 ¬ NH¬ CH3

CH3 16.133 b 16.139 d

16.134 a 16.135 b 16.140 c 16.141 d

16.136 a 16.137 b 16.142 d

17.3 (a) R—NH2

(d)

—

Chapter 17 17.1 3 (N), 2 (O), and 4 (C) (b) R—NH—R (c) R—N—R

16.138 a

R 17.5 (a) yes (b) yes (c) no (d) yes 17.7 (a) 1 (b) 1 (c) 2 (d) 3 17.9 (a) 2 (b) 3 (c) 3 (d) 1 17.11 (a) ethylmethylamine (b) propylamine (c) diethylmethylamine (d) isopropylmethylamine 17.13 (a) 3-pentanamine (b) 2-methyl-3-pentanamine (c) N-methyl3-pentanamine (d) 2,3-butanediamine 17.15 (a) 1-propanamine (b) N-ethyl-N-methylethanamine (c) N-methyl-1-propanamine (d) N-methyl2-butanamine 17.17 (a) 2-bromoaniline (b) N-isopropylaniline (c) N-ethyl-N-methylaniline (d) N-methyl-N-phenylaniline 17.19 NH2 (a) A CH3 O COCH2 OCH3 A CH3 (b) H2N¬CH2 ¬CH2 ¬CH2 ¬ CH2 ¬ CH2 ¬CH2 ¬NH2 (c)

O (d) NH2 O B A B CH3 OCHO COOH CH3 OCHO COCH2 OCH3 A NH2

17.21 CH2O CH2O CH2O CH2O CH3, CH3O CH O CH2O CH2O CH3, A A NH2 NH2 CH3O CH2O CH O CH2O CH3, CH2O CHO CH2OCH3, A A A NH2 NH2 CH3

CH3 A CH3O C O CH2O CH3, CH3O CH O CH O CH3, A A A NH2 CH3 NH2 CH3 A CH3O CH O CH2O CH2, CH3O C O CH2ONH2 A A A NH2 CH3 CH3 17.23 dimethylpropylamine, isopropyldimethylamine, diethylmethylamine 17.25 1-propanamine, 2-propanamine, N-methylethanamine, N,N-dimethylmethanamine 17.27 (a) liquid (b) gas (c) gas (d) liquid 17.29 (a) 3 (b) 3 17.31 Hydrogen bonding is possible for the amine. 17.33 (a) CH3—CH2—NH2; it has fewer carbon atoms. (b) H2N—CH2— CH2—CH2—NH2; it has two amino groups rather than one.

NHOCHO CH3 A CH3

17.41  (a) CH3 ¬ CH2 ¬ NH3 Cl  (b)

(c)



NH3 Br CH3 (d) HCl A CH3 OC ONH2 A CH3

17.43 (a) CH3 O CHONH2 A CH3 (c)



(b) CH3 ONH2 Cl A CH3

NO CH3 A CH3

(d) CH3 ¬ NH ¬ CH3

17.45 (a) propylammonium chloride (b) methylpropylammonium chloride (c) ethyldimethylammonium bromide (d) N,N-dimethylanilinium bromide 17.47 (a) free amine, free base, deprotonated base (b) free amine, free base, deprotonated base (c) protonated base (d) protonated base 17.49 to increase water solubility 17.51 ethylmethylamine hydrochloride 17.53 (a) CH3 ¬ CH2 ¬ CH2 ¬ NH2, NaCl, H2O (b) CH3 OCHONO CH3, NaBr, H 2O A A CH3 CH3 (c) CH3 ¬ CH2 ¬NH¬ CH2 ¬ CH3, NaCl, H2O (d)

CH3 A CH3 OCONH2, A CH3

NaBr, H 2O

17.55 ethylmethylamine and propyl chloride, ethylpropylamine and methyl chloride, methylpropylamine and ethyl chloride

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Answers to Selected Exercises

(c)

(b) CH3 O O CH3 B A B A CH3 O CH2 O CHOCONH2 CH3 OCONO CH3 CH3 O B A CH3 OCHOCH2 O CONHOCH3

(d)

O B HOC ONH2

17.91 H2N—C—NH2 17.93 one of acetamide’s amide hydrogen atoms has been replaced with a hydroxyphenyl group in acetaminophen 17.95 An electronegativity effect induced by the carbonyl oxygen atom makes the lone pair of electrons on the nitrogen atom unavailable. 17.97 (a) 5 (b) 5 17.99 (c) NH3 (a) CH3 ¬NH2 (b) CH3 O A B CH3 OCOOCONOCH3 A A CH3 CH3 (d)

O B COOH

(c)

CH3 O A B CH3 O CHOC OOH, CH3¬ NH2

(d)

CH3 CH3 O A A B CH3 O CHO CHOC OOH , CH3 ¬ NH2

17.103 (a)

O B CH3 O CH2 O CH2 OC OOH , CH3 ¬NH2

(b)

O B  CH3 O CH2 O CH2 OC OOH , CH3 O NH3 Cl

(c)

O B CH3 O CH2 O CH2 O C O O Na, CH3O NH2

(d)

O B C OOH ,

NHOCH3

17.105 diacid and diamine 17.107

冢

H O O H A B B A COCH2 O CH2 O CONO CH2O CH2 O CH2 O CH2 ON

冣

n

17.109 H O A B RO NO C O O O R

17.111 (a)

CH3 O B CH3 O CH2 O CH2 OCH O C O NH2

(b)

O CH3 B CH3 O C O NH OCH O CH3 

(c) CH3 ¬CH2¬NH2¬CH2¬CH3 Cl (d)

CH3  Cl CH3 O NH O CH3

17.112 (a) CH3 ¬ CH2 ¬ NH¬ CH3 (b)

(c) CH3 O CH3 B  CH3 ON OCH3 Cl CH3 O CH2 OCH O C O N O CH3

(d)

CH3 O B CH3 O CH2 OCH O C O O Na

CH3

O O

(a)

O B CH3 O CH2 OCH2 O CH2 O COOH, CH3 ¬ NH2

O

17.59 (a) amine salt (b) quaternary ammonium salt (c) amine salt (d) quaternary ammonium salt 17.61 (a) trimethylammonium bromide (b) tetramethylammonium chloride (c) ethylmethylammonium bromide (d) diethyldimethylammonium chloride 17.63 (a) yes (b) yes (c) no (d) yes 17.65 (a) purine (b) pyrrole (c) imidazole (d) indole 17.67 (a) false (b) true (c) true (d) false 17.69 (a) one (b) one (c) three (d) two 17.71 (a) yes (b) yes (c) yes (d) yes 17.73 (a) true (b) true (c) true (d) false 17.75 (a) O (b) O (c) O B B B ROCO NH2 ROCO NH OR ROCO NOR A R 17.77 (a) yes (b) yes (c) no (d) yes 17.79 (a) monosubstituted (b) disubstituted (c) unsubstituted (d) monosubstituted 17.81 (a) secondary amide (b) tertiary amide (c) primary amide (d) secondary amide 17.83 (a) N-ethylethanamide (b) N,N-dimethylpropanamide (c) butanamide (d) 2-chloropropanamide 17.85 (a) N-ethylacetamide (b) N,N-dimethylpropionamide (c) butyramide (d) 2-chloropropionamide 17.87 (a) propanamide (b) N-methylpropanamide (c) 3,5-dimethylhexanamide (d) N,N-dimethylbutanamide 17.89

(b)

O

(d) CH3 ¬ CH2 ¬NH ¬CH2 ¬CH3

CH3 O A B CH3 O COOH , CH3 ONHOCHO CH3

O

CH3 A  CH3 ONO CH2 O CH3 Br A CH3 (b) CH3 A CH3 OCHONO CHOCH3 A A CH3 CH3 CH3 (c) A CH3 O CH2 ON OCH2 OCH2 O CH3 Cl A CH3

O

(a)

17.101 (a)

O

17.57

CH3

A-17

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A-18

Answers to Selected Exercises

17.113 (a)

O B CH3 O CH2 O C O NH O CH2 O CH2 O CH3

18.29 (a)

H A A Br OOAOO Cl A CH3

(b) CH3 O NH O CH3 (c)

CH3 O B A ⫹ CH3 O CH2 O CH O C O OH, CH3 O NH3 Cl⫺ ⫹

(d) CH3 O CH2 O NH3, OH⫺ 17.114

O B CH3 O CH2 OC O NH2

O B CH3 O C O NH O CH3

Propanamide

N-methylethanamide

NH

CH2 O CH3

N-ethylmethanamide

N N-dimethylmethanamide N,

CH3

O O

17.115

O CH3 B H O C O N O CH3 O

H

O B C

⫹

CH3 ON O CH2 O CH3 Cl⫺ CH3

17.116 (a) unsubstituted (b) monosubstituted (c) monosubstituted (d) unsubstituted 17.117 (a) amine (b) amide (c) amine (d) amide 17.118 (a) 2,N-dimethylpentanamine (b) 3-methylpentanamide (c) 1,4-pentandiamine (d) 4-bromo-N-ethyl-N-methylpentanamide 17.119 c 17.120 c 17.121 c 17.122 b 17.123 c 17.124 b 17.125 c 17.126 a 17.127 b 17.128 b

Chapter 18 18.1 (a) study of the chemical substances in living organisms and the interactions of these substances with each other (b) chemical substance found within a living organism 18.3 proteins, lipids, carbohydrates, and nucleic acids Chlorophyll

18.5 CO2 ⫹ H2O ⫹ solar energy 888888888n carbohydrates ⫹ O2 Plant enzymes

18.7 serve as structural elements, provide energy reserves 18.9 Carbohydrates are polyhydroxy aldehydes, polyhydroxy ketones, or compounds that yield such substances upon hydrolysis. 18.11 (a) 2 (b) 4 (c) 2 to 10 (d) many (several thousand usually) 18.13 Superimposable objects have parts that coincide exactly at all points when the objects are laid upon each other. 18.15 (a) drill bit (b) hand, foot, ear (c) PEEP, POP 18.17 (a) no (b) no (c) yes (d) yes 18.19 (a) no chiral center (b) Cl Cl A A * CH2 O C O*CH A A A Br Br Br (c)

O

B CH2 O*CH O*CH O*CH O C O H A A A A OH OH OH OH (d) CH2 O*CH O*CH O*CH O*CH O CH2 A A A A A A OH OH OH OH OH OH 18.21 (a) zero (b) two (c) zero (d) zero 18.23 (a) achiral (b) chiral (c) chiral (d) chiral 18.25 Constitutional isomers have a different connectivity of atoms. Stereoisomers have the same connectivity of atoms with different arrangements of the atoms in space. 18.27 the presence of a chiral center and the presence of “structural rigidity”

(b)

CH3 A A Br OOAOO Cl A H

(c)

(d) CH3 CH3 A A A A Br OOAOO H H OOAOO Br A A Cl Cl 18.31 (a) (b) CHO CH2OH A A H A OH C PO A A HO A H HO A H A A HO A H H A OH A CH2OH HO A H CH2OH

(c)

CHO A HO A H A HO A H A HO A H A H A OH CH2OH

(d)

CHO A HO A H A H A OH A HO A H A H A OH CH2OH

18.33 (a) d enantiomer (b) d enantiomer (c) l enantiomer (d) l enantiomer 18.35 (a) diastereomers (b) neither enantiomers nor diastereomers (c) enantiomers (d) diastereomers 18.37 (d) effect on plane-polarized light 18.39 (a) same (b) different (c) same (d) different 18.41 (a) aldose (b) ketose (c) ketose (d) ketose 18.43 (a) aldohexose (b) ketohexose (c) ketotriose (d) ketotetrose 18.45 (a) d-galactose (b) d-psicose (c) dihydroxyacetone (d) l-erythrulose 18.47 (a) carbon 4 (b) carbons 1 and 2 (c) carbons 1 and 2 (d) carbon 2 18.49 (a) aldoses, hexoses, aldohexoses (b) hexoses (c) hexoses (d) aldoses 18.51 (b) (c) CHO CH2OH (d) (a) CHO CHO A A A A H A OH H A OH HO A H C PO A A A OH CH 2 HO A H H A OH HO A H A A A H A OH H A OH H A OH A A A H A OH HO A H H A OH CH2OH CH2OH CH2OH 18.53 (a) d-fructose (b) d-glucose (c) d-galactose 18.55 (a) carbons 1 and 5 (b) carbons 1 and 5 (c) carbons 2 and 5 (d) carbons 1 and 4 18.57 the hydroxyl group orientation on carbon 1 18.59 In fructose the cyclization involves carbons 2 and 5, and in ribose the cyclization involves carbons 1 and 4; both processes give five-membered rings. 18.61 The cyclic and noncyclic forms interconvert; an equilibrium exists between the forms. 18.63 (a) a-d-monosaccharide (b) a-d-monosaccharide (c) b-d-monosaccharide (d) a-d-monosaccharide 18.65 All four structures are hemiacetals.

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Answers to Selected Exercises

18.89

H H (c)

HO HO H

a.

OH

CH2OH A CPO A H A OH A HO A H A H A OH CH2OH

OH O OH CH2OH OH

(c)

OH

OH

OH O CH2OH OH

(d)

OH

OH

OH

OH OH 18.73 (a) reducing sugar (b) reducing sugar (c) reducing sugar (d) reducing sugar 18.75 The aldehyde group in glucose is oxidized to an acid group. The Ag in Tollens solution is reduced to Ag. 18.77 (a) COOH (b) CH2OH COOH (c) CHO (d) A A A A H A OH H A OH H A OH H A OH A A A A HO A H HO A H HO A H HO A H A A A A HO A H HO A H HO A H HO A H A A A A H A OH H A OH H A OH H A OH CH2OH COOH COOH CH2OH 18.79 (a) yes (b) yes (c) yes (d) yes 18.81 (a) alpha (b) beta (c) alpha (d) beta 18.83 (a) methyl alcohol (b) ethyl alcohol (c) ethyl alcohol (d) methyl alcohol 18.85 A glycoside is an acetal formed from a cyclic monosaccharide. A glucoside is a glycoside in which the monosaccharide is glucose. 18.87

CH2OH O

a.

O OCH2 O CH3

OH OH b. OH

OH CH2OH O OH

O OCH3

OH

b. OH

CH2OH O OH

OH

NH A C O A CH3

OH

OH

18.69 (a) a-d-glucose (b) a-d-galactose (c) b-d-mannose (d) a-d-sorbose 18.71 CH2OH (a) (b) CH2OH OH OH O O OH

OH

O B HO O P O OH A CH2 O O OH O

18.91 (a) glucose and fructose (b) glucose (c) glucose and galactose (d) glucose 18.93 The glucose part of the lactose structure has a hemiacetal carbon atom. 18.95 (a) negative (b) positive (c) positive (d) positive 18.97 (a) a(1 S 6) (b) b(1 S 4) (c) a(1 S 4) (d) a(1 S 4) 18.99 (a) alpha (b) beta (c) alpha (d) beta 18.101 (a) reducing sugar (b) reducing sugar (c) reducing sugar (d) reducing sugar 18.103 (a) glucose (b) galactose and glucose (c) glucose and altrose (d) glucose 18.105 they are two names for the same thing 18.107 less than 100 monomer units up to a million monomer units 18.109 (a) correct (b) incorrect (c) incorrect (d) correct 18.111 (a) amylopectin is more abundant (b) amylopectin has the longer polymer chain (c) amylopectin has two types of glycosidic linkages and amylose one type of glycosidic linkage (d) same for both 18.113 (a) correct (b) incorrect (c) incorrect (d) correct 18.115 (a) to neither (b) to cellulose only (c) to neither (d) to both 18.117 (a) correct (b) correct (c) correct (d) incorrect 18.119 anticoagulant for blood 18.121 a lipid molecule that has a carbohydrate unit covalently bonded to it 18.123 interaction between the carbohydrate unit of one cell and a protein imbedded into the cell membrane of another cell. 18.125 Simple carbohydrates are the mono- and disaccharides, and complex carbohydrates are the polysaccharides. 18.127 carbohydrates that provide energy but few other nutrients 18.129 (a) chiral (b) achiral (c) chiral (d) chiral 18.130 (a) no (b) no (c) no (d) yes 18.131 (a) no (b) no (c) yes (d) yes 18.132 CH2OH CH2OH CH2OH CH2OH A A A A C O C O C O C O A A A A H OAO OH HO OAO H H OAO OH HO OAO H A A A A H OAO OH HO OAO H HO OAO H H OAO OH CH2OH CH2OH CH2OH CH2OH B

(d)

HO

H

B

CHO A HO A H A HO A H A H A OH A H A OH CH2OH

H

CHO A A OH A A H A A H A A OH CH2OH

B

(b)

B

CHO A A OH A A H A A OH A A OH CH2OH

B

18.67 (a)

A-19

18.133 3-methylhexane (hydrogen, methyl, ethyl, and propyl groups attached to a carbon atom) 18.134 (a) glucose, fructose (b) glucose (c) glucose (d) glucose 18.135 (a) glucose-derivative (b) glucose (c) glucose-derivative (d) glucose 18.136 (a) strong oxidizing agent (b) ethyl alcohol, H ion (c) water (H ion or enzymes) (d) enzymes 18.137 (a) homopolysaccharides (b) homopolysaccharides, branched polysaccharides (c) homopolysaccharides, unbranched polysaccharides (d) heteropolysaccharides, unbranched polysaccharides 18.138 (a) amylopectin, glycogen (b) amylose, cellulose, chitin (c) chitin (d) cellulose, chitin 18.139 b 18.140 d 18.141 b 18.142 c 18.143 c 18.144 a 18.145 c 18.146 c 18.147 d 18.148 c Chapter 19 19.1 All lipids are insoluble or only sparingly soluble in water. 19.3 (a) insoluble (b) soluble (c) insoluble (d) soluble 19.5 energy-storage lipids, membrane lipids, emulsification lipids, messenger lipids, and protective-coating lipids 19.7 (a) long-chain (b) short-chain (c) long-chain (d) medium-chain 19.9 (a) saturated (b) polyunsaturated (c) polyunsaturated (d) monounsaturated 19.11 In a SFA there are no double bonds in the carbon chain; in a MUFA there is one carbon–carbon double bond in the carbon chain.

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A-20

Answers to Selected Exercises

19.13 (a) neither (b) omega-3 (c) omega-3 (d) neither 19.15 CH3 ¬ 1CH2 2 4 ¬ CH “ CH ¬ CH2 ¬ CH “CH¬ 1CH2 2 7 ¬ COOH 19.17 (a) tetradecanoic acid (b) cis-9-hexadecenoic acid 19.19 as carbon chain length increases melting point increases 19.21 cis double bonds in unsaturated fatty acids bend the carbon chain, which decreases the strength of molecular attractions 19.23 (a) 18:1 acid (b) 18:3 acid (c) 14:0 acid (d) 18:1 acid 19.25 a glycerol molecule and three fatty acid molecules 19.27 one, ester O 19.29 B H2C OOO CO(CH2 )14 OCH3 A O A A B HCOOO CO(CH2 )14 OCH3 AA AA O A B C H2 OOOCO(CH2 )14 OCH3 19.31

S L L

L S L

S S L

S L S

19.33 (a) palmitic, myristic, oleic (b) oleic, palmitic, palmitoleic 19.35 (top) 16 carbon atoms and 1 oxygen atom; (middle) 14 carbon atoms and 1 oxygen atom; (bottom) 18 carbon atoms and 1 oxygen atom 19.37 (a) no difference (b) A triacylglycerol may be a solid or a liquid; a fat is a triacylglycerol that is a solid. (c) A triacylglycerol can have fatty acid residues that are all the same, or two or more different kinds may be present. In a mixed triacylglycerol, two or more different fatty acid residues must be present. (d) A fat is a triacylglycerol that is a solid; an oil is a triacylglycerol that is a liquid. 19.39 (a) not correct (b) not correct 19.41 (a) correct (b) not correct 19.43 (a) nonessential fatty acid (b) essential fatty acid (c) nonessential fatty acid (d) nonessential fatty acid 19.45 (a) glycerol and three fatty acids (b) glycerol and three fatty acid salts 19.47 CH2O CHO CH2 A A A OH OH OH CH3 ¬ 1CH2 2 12 ¬ COOH CH3 ¬ 1CH2 2 14 ¬ COOH CH3 ¬ 1CH2 2 7 ¬ CH“ CH¬ 1CH2 2 7 ¬ COOH 19.49 glycerol, palmitic acid, myristic acid, oleic acid 19.51 CH2O CHO CH2 A A A OH OH OH CH3 ¬ 1CH2 2 12 ¬ COO⫺ Na⫹ CH3 ¬ 1CH2 2 14 ¬ COO⫺ Na⫹ CH3 ¬ 1CH2 2 7 ¬CH“ CH¬ 1CH2 2 7 ¬COO⫺ Na⫹ 19.53 glycerol, sodium palmitate, sodium myristate, sodium oleate 19.55 Carbon–carbon double bond(s) must be present. 19.57 six 19.59 (a) (b) 18:0 18:0 18:0 18:1 18:0 18:1B 18:0 18:1 18:0 18:1A 16:0 16:1 16:0 16:0 16:0 18:0 18:0 16:1

There are two possibilities for converting the 18:2 acid to 18:1 acid depending on which double bond is hydrogenated (denoted as 18:1A and 18:1B).

19.61 Rancidity results from hydrolysis of ester linkages and oxidation of carbon–carbon double bonds. 19.63 glycerol and sphingosine 19.65 g

l y c e r o l

fatty acid fatty acid phosphate

alcohol ⫹

⫹

19.67 HO¬CH2 ¬ CH2 ¬N 1CH3 2 3, HO¬CH2 ¬ CH2 ¬ NH3, ⫹

and HOO CH2 OCHO NH3 A COO⫺ 19.69 The two tails are the carbon chain of sphingosine and the fatty acid carbon chain; the head is the phosphate–alcohol portion of the molecule. 19.71 the two tails 19.73 (a) four (b) two 19.75 They differ in the identity of the amino alcohol group; it is choline in a lecithin and serine in a phosphatidylserine. 19.77 sphingosine

fatty acid mono- or oligosaccharide 19.79 carbohydrate group versus a phosphate–alcohol group 12 19.81 17 11 13 2 3

1 4

10 5

9 6

14

16 15

8 7

19.83 —OH on carbon 3, —CH3 on carbons 10 and 13, and a hydrocarbon chain on carbon 17 19.85 “Good cholesterol” is that present in HDLs, and “bad cholesterol” is that present in LDLs. 19.87 phospholipids, sphingoglycolipids, and cholesterol 19.89 a two-layer structure of lipid molecules with nonpolar “tails” in the interior and polar “heads” on the exterior 19.91 creates “open” areas in the bilayer 19.93 a membrane protein that penetrates the interior of the lipid bilayer (cell membrane) 19.95 Protein help is required in facilitated transport but not in passive transport. 19.97 (a) active transport (b) facilitated transport (c) active transport (d) passive transport and facilitated transport 19.99 a substance that can disperse and stabilize water-insoluble substances as colloidal particles in an aqueous solution 19.101 tri- or dihydroxy versus monohydroxy; oxidized side chain amidified to an amino acid versus nonoxidized side chain 19.103 amino acid glycine versus amino acid taurine 19.105 bile fluid 19.107 gall bladder 19.109 sex hormones, adrenocortical hormones 19.111 estradiol has an —OH on carbon 3, while testosterone has a ketone group at this location; testosterone has an extra —CH3 group at carbon 10 19.113 (a) adrenocorticoid hormone (b) sex hormone (c) adrenocorticoid hormone (d) sex hormone 19.115 (a) control Na⫹/K⫹ ion balance in cells and body fluids (b) responsible for secondary male characteristics (c) controls glucose metabolism and is an anti-inflammatory agent (d) responsible for secondary female characteristics 19.117 Prostaglandins have a bond between carbons 8 and 12 that creates a cyclopentane ring structural feature. 19.119 a prostaglandin is similar to a leukotriene but has a cyclopentane ring formed by a bond between C8 and C12 19.121 inflammatory response, production of pain and fever, blood pressure regulation, induction of blood clotting, control of some reproductive functions, regulation of sleep/wake cycle

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Answers to Selected Exercises

19.123 long-chain alchohol

long-chain fatty acid

19.125 mixture of esters involving a long-chain fatty acid and a longchain alcohol versus a long-chain alkane mixture 19.127 (a) neither (b) glycerol-based (c) neither (d) neither 19.128 (a) no (b) no (c) yes (d) no 19.129 (a) sphingomyelins (b) steroids (c) prostaglandins (d) cerebrosides 19.130 (a) energy-storage lipids (b) messenger lipids (c) membrane lipids (d) messenger lipids 19.131 (a) glycerolipid (b) sphingolipid (c) glycerolipid and phospholipid (d) sphingolipid and phospholipid 19.132 (a) 3, 0, 0 (b) 2, 1, 0 (c) 0, 1, 1 (d) 4, 0, 0 19.133 (a) no (b) yes (c) yes (d) no 19.134 b 19.135 a 19.136 b 19.137 a 19.138 c 19.139 d 19.140 c 19.141 a 19.142 c 19.143 a

Chapter 20 20.1 amino acids 20.3 15% by mass 20.5 (a) yes (b) no (c) no (d) yes 20.7 the identity of the R group (side chain) 20.9 (a) phenylalanine, tyrosine, tryptophan (b) methionine, cysteine (c) aspartic acid, glutamic acid (d) serine, threonine, tyrosine 20.11 An amino group is part of the side chain. 20.13 The side chain covalently bonds to the amino acid’s amino group, producing a cyclic structure. 20.15 (a) alanine (b) leucine (c) methionine (d) tryptophan 20.17 asparagine, glutamine, isoleucine, tryptophan 20.19 (a) polar neutral (b) polar acidic (c) nonpolar (d) polar neutral 20.21 L family 20.23 (a) COOH COOH (b) H2N

H

H

NH2

CH2 A OH

CH2 A OH

COOH

(c) H

(d)

NH2

COOH H2N

H CH2 A CHO CH3 A CH3

CH3

20.25 They exist as zwitterions. 20.27 (a) H (b) ⫹

COO⫺

H3N

CH2 A CHO CH3 A CH3 H

(c) ⫹

CHO CH3 A CH2 A CH3 H

(d) ⫹

COO

H

H ⫹

(b) COO⫺

H3N CH2 A OH

COO⫺

H3N

CH2 A SH 20.29 (a)

COO⫺

H3N

⫺

H3N

H ⫹

H ⫹

H3N

COOH CH2 A OH

(c)

H H2N

(d) ⫺

COO

A-21

H ⫹

H3N

COOH

CH2 CH2 A A OH OH 20.31 the pH at which zwitterion concentration in a solution is maximized 20.33 Two —COOH groups are present, which deprotonate at different pH values. 20.35 (a) toward positive electrode (b) isoelectric (c) toward negative electrode (d) toward positive electrode 20.37 Aspartic acid migrates toward the positive electrode, histidine migrates toward the negative electrode, and valine does not migrate. 20.39 They react with each other to produce a covalent disulfide bond. 20.41 9COOH and 9NH2 20.43 O H O H B A B A ⫹ H3NO CHOCONO CHOCONO CHOCOO⫺ A A A CHO CH3 CH2 CH2 A A SH CH3 20.45 Ser is the N-terminal end of Ser–Cys and Cys is the N-terminal end of Cys–Ser. 20.47 Ser–Val–Gly, Val–Ser–Gly, Gly–Ser–Val, Ser–Gly–Val, Val–Gly–Ser, Gly–Val–Ser 20.49 (a) Ser–Ala–Cys (b) Asp–Thr–Asn 20.51 two in each 20.53 (a) serylcysteine (b) glycylalanylvaline (c) tyrosylaspartylglutamine (d) leucyllysyltryptophylmethionine 20.55 peptide bonds and a-carbon 9CH groups 20.57 (a) Both are nonapeptides with six of the residues held in the form of a loop by a disulfide bond. (b) They differ in the identity of the amino acid present at two positions in the nonapeptide. 20.59 They bind at the same sites. 20.61 Glu is bonded to Cys through the side-chain carboxyl group rather than through the a-carbon carboxyl group. 20.63 Monomeric proteins contain a single peptide chain and multimeric proteins have two or more peptide chains. 20.65 (a) true (b) false (c) true (d) true 20.67 the order in which the amino acids are bonded to each other 20.69 peptide bond 20.71 a helix, b pleated sheet 20.73 Intermolecular involves two separate chains and intramolecular involves a single chain bending back on itself. 20.75 Yes, both a helix and b pleated sheet can occur at different regions in the same chain. 20.77 It confers flexibility to the protein, allowing it to interact with several different substances. 20.79 disulfide bonds, electrostatic interactions, hydrogen bonds, and hydrophobic interactions 20.81 (a) nonpolar (b) polar neutral R groups (c) 9SH groups (d) acidic and basic R groups 20.83 (a) hydrophobic (b) electrostatic (c) disulfide bond (d) hydrogen bonding 20.85 the organization among the various peptide chains in a multimeric protein 20.87 They are the same. 20.89 (a) fibrous: generally water-insoluble; globular: generally water-soluble (b) fibrous: support and external protection; globular: involvement in metabolic reactions 20.91 (a) fibrous (b) fibrous (c) globular (d) globular 20.93 a-Keratin has a double-helix structure and collagen a triple-helix structure. 20.95 (a) contractile protein (b) storage protein (c) transport protein (d) messenger protein 20.97 Yes, both Ala and Val are products in each case. 20.99 Drug hydrolysis would occur in the stomach. 20.101 Ala–Gly–Met–His–Val–Arg 20.103 five: Ala–Gly–Ser, Gly–Ser– Tyr, Ala–Gly, Gly–Ser, Ser–Tyr 20.105 secondary, tertiary, and quaternary 20.107 same primary structure 20.109 4-hydroxyproline and 5-hydroxylysine 20.111 They are involved with cross-linking. 20.113 An antigen is a substance foreign to the human body, and an antibody is a substance that defends against an invading antigen. 20.115 four polypeptide chains that have constant and variable amino acid regions; two chains are longer than the other two; 1%–12% carbohydrates present; long and short chains are connected through disulfide linkages 20.117 a spherical structure with an inner core of lipid material

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Answers to Selected Exercises

surrounded by a shell of phospholipids, cholesterol, and proteins 20.119 chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins 20.121 the lipid/protein mass ratio 20.123 (a) transport dietary triacylglycerols from the intestine to various locations (b) transport cholesterol from the liver to cells throughout the body 20.125 (a) tertiary (b) tertiary (c) secondary (d) primary 20.126 (a) alanine (b) leucine (c) threonine (d) aspartic acid 20.127 (a) ⫹1 (b) ⫹1 (c) ⫹1 (d) ⫹3 20.128 (a) ⫺1 (b) ⫺1 (c) ⫺4 (d) ⫺1 20.129 COOH COOH COOH COOH H H H H NH2 H2N NH2 H2N H3C

H

H

H

CH3

CH3

H

H3C

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

20.130 (a) 24 (b) 12 (c) 6 20.131⫹ ⫹ (a) H3N CH COOH; H3N CH CH2

CH3

OH (b) H2N CH CH2

⫹

COOH; H3N CH

COOH

CH2 SH

COO⫺; H2N CH CH3

COO⫺; H2N CH

COO⫺

CH2

OH SH 20.132 (a) simple protein, fibrous protein (b) conjugated protein, globular protein (c) conjugated protein, globular protein (d) conjugated protein, fibrous protein, glycoprotein 20.133 c 20.134 b 20.135 d 20.136 b 20.137 a 20.138 d 20.139 c 20.140 a 20.141 a 20.142 a

Chapter 21 21.1 catalyst 21.3 larger molecular size, activity regulated by other substances 21.5 (a) conjugated (b) conjugated (c) simple (d) conjugated 21.7 A coenzyme is a cofactor that is an organic substance. A cofactor can be an inorganic or an organic substance. 21.9 to provide additional functional groups 21.11 (a) yes (b) no (c) yes (d) yes 21.13 (a) add a carboxylate group to pyruvate (b) remove H2 from an alcohol (c) reduce an L-amino acid (d) hydrolyze maltose 21.15 (a) sucrase (or sucrose hydrolase) (b) pyruvate decarboxylase (c) glucose isomerase (d) lactate dehydrogenase 21.17 (a) pyruvate (b) galactose (c) an alcohol (d) an L-amino acid 21.19 (a) isomerase (b) lyase (c) ligase (d) transferase 21.21 (a) isomerase (b) lyase (c) transferase (d) hydrolase 21.23 (a) decarboxylase (b) lipase (c) phosphatase (d) dehydrogenase 21.25 the portion of an enzyme actually involved in the catalysis process 21.27 The substrate must have the same shape as the active site. 21.29 interactions with amino acid R groups 21.31 (a) accepts only one substrate (b) accepts substrate with a particular type of bond 21.33 absolute specificity and stereochemical specificity 21.35 (a) absolute (b) stereochemical 21.37 Rate increases until enzyme denaturation occurs. 21.39 Enzymes vary in the number of acidic and basic amino acids present. 21.41

irreversible (c) reversible noncompetitive, irreversible (d) reversible noncompetitive 21.51 enzyme that has quaternary structure and more than one binding site 21.53 The product of a subsequent reaction in a series of reactions inhibits a prior reaction. 21.55 A zymogen is an inactive precursor for a proteolytic enzyme. 21.57 so that they will not destroy the tissues that produce them 21.59 process in which enzyme activity is altered by covalently modifying the structure of the enzyme 21.61 ATP molecules 21.63 protein kinases 21.65 competitive inhibition of the conversion of PABA to folic acid 21.67 has absolute specificity for bacterial transpeptidase 21.69 the threat of biological weapon use by terrorists 21.71 tissue plasminogen activator, which activates an enzyme that dissolves blood clots 21.73 forms of the same enzyme with slightly different amino acid sequences 21.75 dietary organic compound needed by the body in trace amounts 21.77 (a) fat-soluble (b) watersoluble (c) water-soluble (d) water-soluble 21.79 (a) likely (b) unlikely (c) unlikely (d) unlikely 21.81 serves as a cosubstrate in the formation of collagen; general antioxidant for water-soluble substances in body fluids 21.83 coenzymes 21.85 (a) no (b) yes (c) yes (d) no 21.87 alcohol, aldehyde, acid 21.89 Cell differentiation is the process whereby immature cells change in structure and function to become specialized cells. Vitamin A binds to protein receptors in the process. 21.91 They differ only in the identity of the side chain present. 21.93 to maintain normal blood levels of calcium and phosphate ion so that bones can absorb these minerals 21.95 a-tocopherol 21.97 antioxidant effect 21.99 in the length and degree of unsaturation of the side chain present 21.101 phylloquinone is an alternate name for vitamin K1 and menaquinones is an alternate name for the various forms of vitamin K2 21.103 (a) An apoenzyme is the protein portion of a conjugated enzyme; a proenzyme is an inactive precursor of an enzyme. (b) A simple enzyme is pure protein; an allosteric enzyme has two or more protein chains and two binding sites. (c) A coenzyme is an organic cofactor, and an isoenzyme is one of several similar forms of an enzyme. (d) A conjugated enzyme has both a protein and a nonprotein portion; holoenzyme is just another name for a conjugated enzyme. 21.104 (a) alcohol, C"C ester (b) double bond, alcohol (c) double bond, alcohol (d) double bond, ketone 21.105 (a) no (b) no (c) yes (d) yes 21.106 (a) vitamin C (b) vitamin E (c) vitamin D (d) vitamin K 21.107 (a) vitamin A (b) vitamin A (c) vitamin C (d) vitamin E 21.108 (a) addition of a group to, or removal of a group from, a double bond in a manner that does not involve hydrolysis or oxidation–reduction (b) bonding together of two molecules with the involvement of ATP (c) hydrolysis reactions (d) transfer of functional groups between two molecules 21.109 (a) ethanol (b) zinc ion (c) protein molecule (d) alcohol dehydrogenase 21.110 (a) tissue plasminogen activator (b) lactate dehydrogenase (c) creatine phosphokinase (d) aspartate transaminase 21.111 b 21.112 b 21.113 c 21.114 d 21.115 d 21.116 d 21.117 c 21.118 c 21.119 c 21.120 a Chapter 22 22.1 deoxyribonucleic acid 22.3 need for the synthesis of proteins 22.5 within the cell nucleus 22.7 nucleotides 22.9 three 22.11 Ribose has both an 9H group and an 9OH group on carbon 2; deoxyribose has 2 9H atoms on carbon 2. 22.13 (a) pyrimidine (b) pyrimidine (c) purine (d) purine 22.15 (a) one (b) four (c) one 22.17 (a) adenine (b) guanine (c) thymine (d) uracil 22.19 (a) ribose (b) deoxyribose (c) deoxyribose (d) ribose 22.21 (a) false (b) false (c) false (d) false 22.23 O O⫺ H CH 3 HOCH2 O A N OH O P P O OH N

21.43 nothing; the rate remains constant 21.45 microbial enzymes that survive under extreme temperature and pressure conditions 21.47 no; only one molecule may occupy the active site at a given time 21.49 (a) reversible competitive (b) reversible noncompetitive,

A

O

A

HO

H

O⫺

H 22.25 a pentose sugar and a phosphate 22.27 base sequence 22.29 5⬘ end has a phosphate group attached to the 5⬘ carbon; 3⬘ end has

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Answers to Selected Exercises

a hydroxyl group attached to the 3 carbon 22.31 a phosphate group and two pentose sugars 22.33 O H CH 3 N O A O O P P O O O CH 2 O N A

O O

H O A

O P P OOOCH2 A

O

N O

N

N N

H NH 2

OH OH 22.35 (a) two polynucleotide chains coiled around each other in a helical fashion (b) The nucleic acid backbones are the outside, and the nitrogencontaining bases are on the inside. 22.37 (a) 36% (b) 14% (c) 14% 22.39 A G–C pairing involves 3 hydrogen bonds, and an A–T pairing involves 2 hydrogen bonds. 22.41 They are the same. 22.43 5 TAGCC 3 22.45 (a) 3 TGCATA 5 (b) 3 AATGGC 5 (c) 5 CGTATT 3 (d) 3 TTGACC 5 22.47 20 hydrogen bonds 22.49 catalyzes the unwinding of the double helix structure 22.51 (a) 3 TGAATC 5 (b) 3 TGAATC 5 (c) 5 ACTTAG 3 22.53 The unwound strands are antiparallel (5 : 3 and 3 : 5 ). Only the 5 : 3 strand can grow continuously. 22.55 a DNA molecule bound to a group of small proteins 22.57 DNA 22.59 RNA 22.61 (1) RNA contains ribose instead of deoxyribose, (2) RNA contains the base U instead of T, (3) RNA is single-stranded rather than double-stranded, and (4) RNA has a lower molecular mass. 22.63 (a) hnRNA (b) tRNA (c) tRNA (d) hnRNA 22.65 (a) nuclear region (b) extranuclear region (c) extranuclear region (d) both nuclear and extranuclear regions 22.67 a strand of DNA 22.69 causes a DNA helix to unwind; links aligned ribonucleotides together 22.71 T–A, A–U, G–C, C–G 22.73 3 UACGAAU 5 22.75 3 AAGCGTC 5 22.77 Exons convey genetic information whereas introns do not. 22.79 3 AGUCAAGU 5 22.81 (a) hnRNA (b) snRNA 22.83 a mechanism by which a number of proteins that are variations of a basic structural motif can be produced from a single gene 22.85 A three-nucleotide sequence in mRNA that codes for a specific amino acid 22.87 (a) Leu (b) Asn (c) Ser (d) Gly 22.89 (a) CUC, CUA, CUG, UUA, UUG (b) AAC (c) AGC, UCU, UCC, UCA, UCG (d) GGU, GGC, GGA 22.91 The base T cannot be present in a codon. 22.93 Met–Lys–Glu–Asp–Leu 22.95 A cloverleaf shape with three hairpin loops and one open side. 22.97 covalent bond (ester) 22.99 anticodons written in the 5 -to-3 direction: (a) UCU (b) ACG (c) AAA (d) UUG 22.101 (a) Gly (b) Leu (c) Ala (d) Leu 22.103 (a) UCU, UCC, UCA, UCG, AGU, AGC (b) UUA, UUG, CUU, CUC, CUA, CUG (c) AUU, AUC, AUA (d) GGU, GGC, GGA, GGG 22.105 an rRNA-protein complex that serves as the site for the translation phase of protein synthesis 22.107 mostly rRNA with some protein 22.109 an amino acid reacts with ATP, the resulting complex reacts with tRNA 22.111 A site 22.113 initial Met residue is removed; covalent modification occurs if needed; completion of folding of protein occurs 22.115 Gly: GGU, GGC, GGA or GGG; Ala: GCU, GCC, GCA or GCG; Cys: UGU or UGC; Val: GUU, GUC, GUA or GUG; Tyr: UAU or UAC 22.117 (a) Gly–Tyr–Ser–Ser–Pro (b) Gly–Tyr–Ser–Ser–Pro (c) Gly– Tyr–Ser–Ser–Thr 22.119 a DNA or an RNA molecule with a protein coating 22.121 (1) attaches itself to cell membrane, (2) opens a hole in the membrane, and (3) injects itself into the cell 22.123 contains a “foreign” gene 22.125 host for a “foreign” gene

A-23

22.127 Recombinant DNA is incorporated into a host cell. 22.129 5' 3' C C A

A G C T T G A C

G G T T C G A 5' 3' 22.131 to produce many copies of a specific DNA sequence in a relatively short time 22.133 a short nucleotide chain bound to the template DNA strand to which new nucleotides can be attached 22.135 dATP stands for an ATP in which deoxyribose is present; ddATP stands for an ATP in which dideoxyribose is present. 22.137 (a) 5 GCCGACTACT 3 (b) 5 AGTAGTCGGC 3 22.139 (a) Thymine has a methyl group on carbon-5 that uracil lacks. (b) Adenine is 6-aminopurine, and guanine is 2-amino-6-oxopurine. 22.140 (a) 3 GTATGTCGGACCTTCGAG 5 (b) 3 GUAUGUCGGACCUUCGAG 5 (c) 3 GUA–UGU–CGG–ACC– UUC–GAG 5 (d) 5 CAU–ACA–GCC–UGG–AAG–CUC 3 (e) Glu–Leu–Pro–Gly–Lys–Met 22.141 (a) 1 (b) 4 (c) 2 (d) 4 22.142 (a) 3 (b) 2 (c) 1 (d) 3 22.143 (a) 3 (b) 1 (c) 2 and 4 (d) 1, 2, 3, and 4 22.144 (a) 1 (b) 2 (c) 4 (d) 3 22.145 A 22.146 (a) 2.9 billion base pairs (b) 20,000–25,000 genes (c) 2% of base pairs 22.147 c 22.148 a 22.149 c 22.150 a 22.151 b 22.152 d 22.153 a 22.154 b 22.155 b 22.156 b

Chapter 23 23.1 anabolism—synthetic; catabolism—degradative 23.3 a series of consecutive biochemical reactions 23.5 Large molecules are broken down to smaller ones; energy is released. 23.7 Prokaryotic cells have no nucleus, and the DNA is usually a single circular molecule. Eukaryotic cells have their DNA in a membraneenclosed nucleus. 23.9 An organelle is a small structure within the cell cytosol that carries out a specific cellular function. 23.11 inner membrane 23.13 region between inner and outer membranes 23.15 adenosine triphosphate 23.17 phosphate

phosphate phosphate

ribose adenine

23.19 three phosphates versus one phosphate 23.21 adenine versus guanine 23.23 ADP is produced from the hydrolysis of ATP. 23.25 flavin adenine dinucleotide 23.27 flavin ribitol ADP 23.29 nicotinamide ribose phosphate adenine ribose phosphate 23.31 nicotinamide subunit 23.33 (a) FADH2 (b) NAD 23.35 (a) nicotinamide (b) riboflavin 23.37 2-aminoethanethiol pantothenic acid

phosphorylated ADP

23.39 a compound with a greater free energy of hydrolysis than is typical for a compound 23.41 free monophosphate species 23.43 (a) phosphoenolpyruvate (b) creatine phosphate (c) 1,3-bisphosphoglycerate (d) AMP 23.45 (1) digestion, (2) acetyl group formation, (3) citric acid cycle, (4) electron transport chain and oxidative phosphorylation 23.47 tricarboxylic acid cycle, Krebs cycle 23.49 acetyl CoA 23.51 (a) 2 (b) 1 (c) 2 (Steps 3, 8) (d) 2 (Steps 2, 7) 23.53 (a) Steps 3, 4, 6, 8 (b) Step 2 (c) Step 7 23.55 succinate 1 OOC¬CH2¬CH2¬COO 2; fumarate 1 OOC¬CH“CH¬COO 2 ; malate OOCOCH2O CHOCOO ; A OH

1

1



2

1

O B OOCOCH2O COCOO

oxaloacetate 23.57 oxidation and decarboxylation 23.59 (a) NAD (b) FAD 23.61 (a) isocitrate, a-ketoglutarate (b) fumarate, malate (c) malate, oxaloacetate (d) citrate, isocitrate 23.63 respiratory chain 23.65 O2 23.67 (a) FMN (b) CoQH2 23.69 (a) oxidized (b) oxidized (c) reduced (d) oxidized 23.71 (a) oxidation (b) reduction (c) oxidation

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A-24

Answers to Selected Exercises

(d) reduction 23.73 (a) I (b) I, II, III (c) III (d) IV 23.75 CoQH2 23.77 two 23.79 (a) FADH2, 2 Fe(II)SP, CoQH2 (b) FMNH2, 2 Fe2⫹, CoQH2 23.81 ATP synthesis from ADP Pi using energy from the electron transport chain 23.83 protons (H⫹ ions) 23.85 intermembrane space 23.87 ATP synthase 23.89 Protons flow through ATP synthase complex. 23.91 2.5 ATP molecules 23.93 They enter the ETC at different stages. 23.95 It is an intermediate amount of free energy, higher than some reactions and lower than others. 23.97 (a) ATP to ADP (b) ATP to ADP 23.99 reactive oxygen species 23.101 (a) 2O 2 1 NADPH ¡ 2O 22 1 NADP 1 1 H 1 (b) 2O 22 1 2H 1 ¡ H 2O 2 1 O 2 23.103 (a) 2 (b) 2 (c) 1 (d) 2 23.104 (a) 2 (b) 1 (c) 1 (d) 2 23.105 (a) 4 (b) 3 and 4 (c) 1, 2, 3, and 4 (d) 3 23.106 (a) 1 (b) 4 (c) 4 (d) 2 23.107 The products from the CAC, which are FADH2 and NADH, are the starting reactants for the ETC. 23.108 (a) inside mitochondria matrix (b) inside mitochondria (inner membrane) 23.109 FAD is the oxidizing agent for carbon–carbon double bond formation. 23.110 Reduced coenzymes are oxidized, and ADP is phosphorylated. 23.111 a 23.112 b 23.113 d 23.114 b 23.115 c 23.116 c 23.117 a 23.118 d 23.119 c 23.120 d

Chapter 24 24.1 mouth, salivary a-amylase 24.3 small intestine, pancreas 24.5 outer membranes of intestinal mucosal cells, sucrose hydrolysis 24.7 glucose, galactose, fructose 24.9 glucose 24.11 NAD⫹ 24.13 formation of glucose 6-phosphate, a species that cannot cross cell membranes 24.15 dihydroxyacetone phosphate, glyceraldehyde 3-phosphate 24.17 two 24.19 two 24.21 Steps 1, 3, and 6 24.23 cytosol 24.25 (a) glucose 6-phosphate (b) 2-phosphoglycerate (c) phosphoglyceromutase (d) ADP 24.27 (a) Step 10 (b) Step 1 (c) Step 8 (d) Step 6 24.29 (a) ⫹2 (b) ⫹4 24.31 O O (a) B

B

CH3 O C O COOH and CH3 O C O COO⫺ (b) CH2 O OH CH2 O O O P (c) PO OO CH2 A

CPO A

O OH

A

and C P O A

CH2 O OH

A

CH2 O OH

OH (d) COOH

and PO OOCH2 A

CH2OH

A OH

O CH2 O O O P OH A OH

A

CH OOH A

and

CH2OOH

OH CHO A

CH OOH A

CH2OOH 1

4

24.33 CH2 O OO P 2

A

CP O

3

A

CH2 OOH

CHO

and

5

A

CHOOH

6

A

CH2 O OO P

24.35 acetyl CoA, lactate, ethanol 24.37 pyruvate ⫹ CoA ⫹ NAD⫹ acetyl CoA ⫹ NADH ⫹ CO2 24.39 NADH is oxidized to NAD⫹, a substance needed for glycolysis. 24.41 CO2 24.43 glucose ⫹ 2ADP ⫹ 2Pi 2lactate ⫹ 2ATP ⫹ 2H2O 24.45 decreases ATP production by 2 24.47 30 ATP versus 2 ATP 24.49 two 24.51 Glycogenesis converts glucose 6-phosphate to glycogen and glycogenolysis is the reverse process. 24.53 glucose 6-phosphate 24.55 UTP UTP ⫹ ADP 24.59 Step 2 24.61 Glucose 24.57 UDP ⫹ ATP 6-phosphate is converted to glucose in liver cells and used as is in muscle cells. 24.63 as glucose 6-phosphate 24.65 the liver 24.67 two-step pathway for Step 10; different enzymes for Steps 1 and 3 24.69 oxaloacetate 24.71 goes to the liver, where it is converted to glucose 24.73 (a) all four processes (b) glycolysis and gluconeogenesis (c) gluconeogenesis

(d) glycogenesis 24.75 (a) glycolysis (b) glycolysis (c) glycogenesis (d) glycolysis 24.77 (a) gluconeogenesis (b) glycolysis (c) glycogenesis (d) glycogenesis and glycogenolysis 24.79 glucose 6-phosphate 24.81 NADPH is consumed in its reduced form; NADH is consumed in its oxidized form (NAD⫹). 24.83 Glucose 6-phosphate ⫹ 2NADP⫹ ⫹ ribulose 5-phosphate ⫹ CO2 ⫹ 2NADPH ⫹ 2H⫹ 24.85 CO2 H2 O 24.87 increases rate of glyco-gen synthesis 24.89 increases blood glucose levels 24.91 pancreas 24.93 Epinephrine attaches to cell membrane and stimulates the production of cAMP, which activates glycogen phosphorylase. 24.95 glucagon (liver cells) and epinephrine (muscle cells) 24.97 (a) 2 ATP (b) 30 ATP (c) 2 ATP (d) 2 ATP 24.98 (a) 1,2 (b) 2 (c) 3 (d) 4 24.99 (a) when the body requires free glucose (b) anaerobic conditions in muscle; red blood cells (c) when the body requires energy (d) anaerobic conditions in yeast 24.100 (a) 12 moles (b) 4 moles (c) 4 moles (d) 60 moles 24.101 (a) The glucose supply is adequate, and the body does not need energy. (b) The glucose supply is adequate, and the body needs energy. (c) Ribose 5-phosphate or NADPH is needed. (d) The free glucose supply is not adequate. 24.102 b 24.103 b 24.104 b 24.105 d 24.106 c 24.107 a 24.108 b 24.109 c 24.110 d 24.111 c

Chapter 25 25.1 98% 25.3 no effect 25.5 (a) stomach and small intestine (b) stomach (10%) and small intestine (90%) (c) stomach (gastric lipases), small intestine (pancreatic lipases) 25.7 acts as an emulsifier 25.9 monoacylglycerols are the major product 25.11 reassembled into triacylglycerols; converted to chylomicrons 25.13 They have a large storage capacity for triacylglycerols. 25.15 hydrolysis of triacylglycerols in adipose tissue; entry of hydrolysis products into bloodstream 25.17 activates hormone-sensitive lipase 25.19 (a) Step 1 (b) Step 1 (c) Step 2 (d) Step 1 25.21 one 25.23 (a) true (b) false (c) true 2 (d) false 25.25 (a) intermembrane space (b) matrix (c) intermembrane space (d) matrix 25.27 the ATP is converted to AMP rather than ADP 25.29 (a) alkane to alkene (b) alkene to 2⬚ alcohol (c) 2⬚ alcohol to ketone 25.31 trans isomer 25.33 (a) Step 3, turn 2 (b) Step 2, turn 3 (c) Step 4, turn 3 (d) Step 1, turn 2 25.35 compounds a and d 25.37 (a) 7 turns (b) 5 turns 25.39 A cis–trans isomerase converts a cis bond to a trans bond 25.41 (a) glucose (b) fatty acids 25.43 (a) 4 turns (b) 5 acetyl CoA (c) 4 NADH (d) 4 FADH2 (e) 2 highenergy bonds 25.45 64 ATP 25.47 unsaturated fatty acid produces less FADH2 25.49 4 kcal versus 9 kcal 25.51 (1) dietary intakes high in fat and low in carbohydrates, (2) inadequate processing of glucose present, and (3) prolonged fasting 25.53 Ketone body formation occurs when oxaloacetate concentrations are low. 25.55 O O OH O B B A B ⫺ CH3O COCH2 OCOO CH3O CHOCH2 OCOO⫺ O B CH3O COCH3 25.57 (a) acetoacetate, acetone (b) b-hydroxybutyrate (c) acetoacetate (d) acetone 25.59 (a) Step 1 (b) Step 4 (c) Step 1 (d) Step 3 25.61 (a) Steps 1 and 2 (b) Step 2 (c) Step 2 (d) Step 3 25.63 acetoacetate and succinyl CoA are reactants; acetoacetyl CoA and succinate are products 25.65 accumulation of ketone bodies in blood and urine 25.67 cytosol versus mitochondrial matrix 25.69 acyl carrier protein; polypeptide chain replaces phosphorylated AMP 25.71 (a) matrix (b) cytosol (c) cytosol (d) cytosol 25.73 (a) malonyl CoA (b) acetyl ACP (c) malonyl CoA (d) acetyl ACP 25.75 (a) Step 2 (b) Step 3 (c) Step 1 (d) Step 4 25.77 (a) acetoacetyl ACP (b) crotonyl ACP (c) crotonyl ACP (d) acetoacetyl ACP 25.79 (a) condensation (b) hydrogenation (c) dehydration (d) hydrogenation 25.81 needed to convert saturated

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Answers to Selected Exercises

A-25

fatty acids to unsaturated fatty acids 25.83 (a) 6 turns (b) 6 malonyl ACP (c) 6 ATP bonds (d) 12 NADPH 25.85 (a) succinate (b) oxaloacetate (c) malate (d) fumarate 25.87 (a) unsaturated acid (b) ketoacid (c) ketoacid (d) hydroxyacid 25.89 (a) 13–17% (b) 83–87% 25.91 (a) mevalonate (b) isopentenyl pyrophosphate (c) squalene 25.93 (a) fewer than (b) fewer than (c) same as 25.95 (a) fatty acids, cholesterol, and ketone bodies (b) glucose, glycerol, and fatty acids 25.97 (a) b-oxidation pathway (b) lipogenesis (c) glycerol catabolism (d) ketogenesis 25.98 (a) fatty acid catabolism (b) lipogenesis (c) consumption of molecular O2 (d) consumption of molecular O2 25.99 (a) Step 1 (b) Step 1 (c) Step 3 (d) Step 4 25.100 (1), (3), (4), and (2) 25.101 (a) true (b) false (c) false (d) false 25.102 (a) incorrect (b) correct (c) incorrect (d) correct 25.103 (a) correct (b) correct (c) correct (d) correct 25.104 glucose, C8 fatty acid, sucrose, C14 fatty acid 25.105 b 25.106 a 25.107 c 25.108 c 25.109 a 25.110 b 25.111 a 25.112 c 25.113 c 25.114 b

26.27 pyruvate, a-ketoglutarate 26.29 coenzyme that participates in the amino group transfer 26.31 conversion of an amino acid into a keto acid with the release of ammonium ion 26.33 Oxidative deamination produces ammonium ion, and transamination produces an amino acid. 26.35

Chapter 26 26.1 Denaturation occurs in the stomach with gastric juice as the denaturant. 26.3 Pepsinogen is the inactive precursor of pepsin. 26.5 Gastric juice is acidic (1.5–2.0 pH) and pancreatic juice is basic (7.0–8.0 pH). 26.7 Membrane protein molecules facilitate the passage of amino acids through the intestinal wall. 26.9 total supply of free amino acids available for use 26.11 cyclic process of protein degradation and resynthesis 26.13 A positive nitrogen balance has nitrogen intake exceeding nitrogen output; a negative nitrogen balance has nitrogen output exceeding nitrogen intake. 26.15 negative balance; proteins are degraded to get the needed amino acid 26.17 protein synthesis; synthesis of nonprotein nitrogen-containing compounds; nonessential amino acid synthesis; energy production 26.19 (a) essential (b) nonessential (c) nonessential (d) essential 26.21 b and c 26.23 an amino acid and an a-keto acid 26.25 ⫹ (a) NH3 O A B ⫺ HOO CHOCHOCOO ⫹ CH3O COCOO⫺ A CH3 ⫹ O NH3 B A HOO CHOCOCOO⫺ ⫹ CH3O CHOCOO⫺ A CH3

26.39 (a) aspartate (b) glutamate (c) pyruvate (d) a-ketoglutarate O 26.41 B H2NO CONH2

(b)

⫹

NH3 O A B ⫺ ⫺ CH3 OCHOCOO ⫹ OOCOCH2O COCOO⫺ ⫹

(c)

⫹

O NH3 B A ⫺ ⫺ CH3 OC OCOO ⫹ OOCO CH2O CHOCOO⫺

NH3 O A B ⫺ ⫺ HO CHO COO ⫹ OOC OCH2 OCH2 OCOCOO⫺ ⫹

O NH3 B A ⫺ ⫺ HOCOCOO ⫹ OOCOCH2O CH2O CHOCOO⫺ (d)

⫹

NH3 A HOOCHOCHO COO⫺ ⫹ A CH3

O B OOCO CH2OCH2O COCOO⫺

⫺

⫹

O NH3 B A ⫺ ⫺ HOOCHOCOCOO ⫹ OOCOCH2 OCH2 OCHOCOO⫺ A CH3

(a)

O B OOCO CH2O CH2 OCOCOO⫺

⫺

(b)

(c)

O B HS O CH2O COCOO⫺

(d)

O B CH3 OCOCOO⫺

O B CH2O COCOO⫺

26.37 Transamination of the a-keto acid produces the amino acid. ⫹

NH3 CH3 A A CH3 OCHOCH2 OCHOCOO⫺

26.43 carbamoyl phosphate

26.45 an amide group, ⫹

O B O CONH2

O NH2 B B H3NO, H2NO CONHO, H2NO CONHO 26.49 (a) carbamoyl phosphate (b) aspartate 26.51 carbamoyl phosphate 26.53 (a) N2 (b) N3 (c) N1 (d) N4 26.55 (a) citrulline (b) ornithine (c) argininosuccinate (d) carbamoyl phosphate 26.57 equivalent of four ATP molecules 26.59 goes to the citric acid cycle where it is converted to oxaloacetate, which is then converted to aspartate 26.61 a-ketoglutarate, succinyl CoA, fumarate, oxaloacetate 26.63 (a) acetoacetyl CoA and acetyl CoA (b) succinyl CoA and acetyl CoA (c) fumarate and oxaloacetate (d) a-ketoglutarate 26.65 Degradation products can be used to make glucose. 26.67 glutamate 26.69 pyruvate, a-ketoglutarate, 3-phosphoglycerate, oxaloacetate, and phenylalanine 26.71 hydrolyzed to amino acids 26.73 In biliverdin the heme ring has been opened and one carbon atom has been lost (as CO). 26.75 biliverdin, bilirubin, bilirubin diglucuronide, urobilin 26.77 urobilin 26.79 excess bilirubin 26.81 Amino acid carbon skeletons are degraded to acetyl CoA or acetoacetyl CoA; ketogenesis converts these degradation products to ketone bodies. 26.83 converted to body fat stores 26.85 (a) 1 (b) 2 (c) 3 (d) 2 26.86 (a) 1 (b) 3 (c) 3 (d) 2 26.87 (1), (3), (2), and (4) 26.88 (a) 3 (b) 2 (c) 1 (d) 3 26.89 (a) transamination (b) deamination (c) deamination (d) transamination 26.90 (a) 1 (b) 4 (c) 2 (d) 3 26.91 (a) false (b) false (c) true (d) true 26.92 (a) 2 (b) 1 (c) 2 (d) 3 26.93 a 26.94 d 26.95 a 26.96 b 26.97 c 26.98 b 26.99 c 26.100 c 26.101 b 26.102 c 26.47

⫹

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A-26

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Index/Glossary Absolute alcohol, 405 Accutane, 481 Acetal An organic compound in which a carbon atom is bonded to two alkoxy groups (—OR), 460 formation of, from cyclic monosaccharides, 579, 581 hydrolysis of, 460–462 nomenclature for, 462 preparation of, from hemiacetals, 460 Acetaminophen pharmacology of, 538 structure of, 538 Acetoacetate ketogenesis and, 857 ketone body, 854–855 utilization of, as fuel, 857 Acetoacetyl CoA amino acid degradation product, 890 ketogenesis and, 856 lipogenesis and, 861–862 Acetone biochemical production of, acetoacetate and, 855 derivatives of, glycolysis and, 816 ketone body, 854–855 properties of, 450 Acetyl ACP lipogenesis and, 860 structure of, 860 Acetyl CoA amino acid degradation product, 890 cholesterol biosynthesis and, 866 citric acid cycle and, 789–790 ketogenesis and, 856 possible fates of, 869 production of, b oxidation pathway, 847–849 pyruvate oxidation and, 822–823 thioester structure of, 498 Acetyl coenzyme A. See Acetyl CoA Acetyl group The portion of an acetic acid molecule (CH3—COOH) that remains after the —OH group is removed from the carboxyl carbon atom, 785 coenzyme A as carrier of, 785 Achiral molecule A molecule whose mirror images are superimposable, 558 Acid acidic and nonacidic hydrogen atoms within, 257–258 aldaric, 578 aldonic, 578 alduronic, 579 Arrhenius, 253–254 Brønsted–Lowry, 254–257 carboxylic, 473–484 chemical formula notation for, 257–258 diprotic, 257 fatty, 609–614 monoprotic, 257–258

neutralization of, 262–263 pKa of, 269–270 polyprotic, 257 strength of, 258–260 strong, 258–259 summary diagram concerning, 271 triprotic, 257 weak, 259–260 Acid anhydride A carboxylic acid derivative in which the —OH portion of the carboxyl group has been replaced with a O B group, 501 O O C O R⬘ general formula for, 501 hydrolysis of, 502 nomenclature for, 502 phosphoric acid, 504–505 prepartion of, 502 Acid–base indicator A compound that exhibits different colors depending on the pH of its solution, 282, 284 need for in titrations, 282, 284 Acid–base neutralization chemical reaction A chemical reaction between an acid and a hydroxide base in which a salt and water are the products, 262 equations for, 262–263 Acid–base titration A neutralization reaction in which a measured volume of an acid or a base of known concentration is completely reacted with a measured volume of a base or an acid of unknown concentration, 282 indicator use in, 282, 284 use of data from, in calculations, 284–285 Acid chloride A carboxylic acid derivative in which the —OH portion of the carboxyl group has been replaced with a —Cl atom, 501 general formula for, 501 hydrolysis of, 501 nomenclature for, 501 preparation of, 501 Acid inhibitor, 265 Acid ionization constant (Ka) The equilibrium constant for the reaction of a weak acid with water, 260 calculating value of, 260–261 listing of, selected acids, 260 mathematical expression for, 260 Acid rain effects of, 272 formation of, 272 pH values for, 272 Acidic polysaccharide A polysaccharide with a disaccharide repeating unit in which one of the disaccharide components is an amino sugar and in which one or both disaccharide components has a negative charge due to a sulfate group or a carboxyl group, 595

heparin, 596 hyaluronic acid, 595–596 Acidic solution An aqueous solution in which the concentration of H3O⫹ ion is higher than that of OH⫺ ion; an aqueous solution whose pH is less than 7.0, 264, 268 hydronium ion concentration and, 264–266 pH value and, 268 summary diagram concerning, 271 Acidosis A body condition in which the pH of blood drops from its normal value of 7.4 to 7.1–7.2, 279 keto, 858 metabolic, 279 respiratory, 279 ACP complex. See Acyl carrier protein complex Acrolein, 449 Acrylamide, 534 Acrylic acid, 479 Actin, 682 Activation energy The minimum combined kinetic energy that colliding reactant particles must possess in order for their collision to result in a chemical reaction, 233 energy diagrams and, 235 Active site The relatively small part of an enzyme’s structure that is actually involved in catalysis, 704 function of, in enzyme, 704 Active transport The transport process in which a substance moves across a cell membrane, with the aid of membrane proteins, against a concentration gradient with the expenditure of cellular energy, 639 process of, characteristics for, 639–640 Acyl-carnitine, shuttle system participant, 847 Acyl carrier protein complex formation of, lipogenesis and, 860–861 Acyl CoA, beta oxidation pathway and, 847–848 Acyl group The portion of a carboxylic acid that remains after the —OH group is removed from the carboxyl carbon atom, 502 compounds containing, examples of, 502–503 fatty acid oxidation and, 847 nomenclature for, 503 Acyl transfer reaction A chemical reaction in which an acyl group is transferred from one molecule to another, 503 examples of, 503 peptide synthesis and, 761 Addition polymer A polymer in which the monomers simply “add together” with no other products formed besides the polymer, 378 butadiene-based, 381

A-27

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A-28

Index/Glossary

Addition polymer (Continued) ethene-based, 379–381 formulas of, notation for, 379 recycling for, 380–381 Addition reaction A chemical reaction in which atoms or groups of atoms are added to each carbon atom of a carbon-carbon multiple bond in a hydrocarbon or hydrocarbon derivative, 373 alkene, 373–378 symmetrical, 374–378 unsymmetrical, 375–378 Adenine nucleotide subunit, 735–737 structure of, 735–737 Adenosine diphosphate hydrolysis of, 781–782 phosphorylated, 784–785 strained bond within, 782 structural subunits in, 781 Adenosine monophosphate structural subunits in, 781 Adenosine phosphates general structures for, 781 phosphoanhydride bonds and, 781 phosphoryl groups and, 781 Adenosine triphosphate consumption of, gluconeogenesis and, 831–832 consumption of, lipogenesis and, 862–863 free energy production and, 804 hydrolysis of, 781–782 production amounts, common metabolic pathway and, 803–804 production amounts, complete oxidation of glucose and, 826–827 production of, beta oxidation pathway and, 851–852 production of, common metabolic pathway and, 802–804 production of, fatty-acid oxidation–glucose oxidation comparision, 853–854 production of, glycolysis and, 818–819 production of, oxidative phosphorylation and, 800–802 strained bonds within, 782 structural subunits in, 781 turnover rate, 804 Adipocyte A triacylglycerol-storing cell, 845 Adipose tissue Tissue that contains large numbers of adipocyte cells, 845 locations for, within human body, 845 triacylglycerol storage and, 845 ADP. See Adenosine diphosphate Adrenaline, 528–529 Adrenocorticoid hormone, types of, 643 Advil, 480 Aerobic process oxygen conditions for, 822 pyruvate oxidation to acetyl CoA, 822–823 AIDS immunoglobulins and, 689 retrovirus and, 765 Airbags, operation of, 167 Alcohol An organic compound in which an 9OH group is bonded to a saturated carbon atom, 400 absolute, 405

chemical reaction summary for, 418 classifications of, 410–411 combustion, 411 commonly encountered, 403–407 dehydration, intermolecular, 413–415 dehydration, intramolecular, 411–415 denatured, 405 functional group for, 400 generalized formula for, 400 grain, 404 halogenation of, 417–418 hydrogen-bonding and, 409–410 IUPAC-common name contrast for, 402 line-angle structural formulas for, 401 nomenclature of, 401–403 oxidation of, 415–417 physical properties of, 407–410 physical-state summary for, 409 polyhydroxy, 403 polymeric, 418–419 preparation of, from aldehydes, 410 preparation of, from alkenes, 410 preparation of, from ketones, 410 primary, 410–411 rubbing, 405 secondary, 410–411 sugar, 579 sulfur analogs of, 429–431 tertiary, 410–411 wood, 404 Aldaric acid, 578 Aldehyde A carbonyl-containing organic compound in which the carbonyl carbon atom is bonded to at least one hydrogen atom, 444 chemical reaction summary for, 462 commonly encountered, 450–451 diabetes testing and, 456 functional group for, 444 generalized formula for, 444 hemiacetal formation and, 458–459 IUPAC-common name contrast for, 447 lachrymatory, 449 line-angle structural formulas for, 446 nomenclature of, 445–447 oxidation of, 455–457 physical properties of, 451–453 physical-state summary for, 451 preparation of, from alcohols, 415–417, 453–455 reaction with alcohols, 458–459 reaction with Benedict’s solution, 455–456 reaction with Tollens solution, 455–456 reduction of, 457 thio, 464 Aldonic acid, 578 Aldose A monosaccharide that contains an aldehyde functional group, 569 common, listing of, 571 Aldosterone, 643 Alduronic acid, 579 Aleve, 480 Alkali metal A general name for any element in Group IA of the periodic table excluding hydrogen, 60 periodic table location of, 60, 75

Alkaline earth metal A general name for any element in Group IIA of the periodic table, 60 periodic table location of, 60, 75 Alkaline solution, 264 Alkaloid A nitrogen-containing organic compound extracted from plant material, 529 atropine, 529 caffeine, 526 chocolate, 531 medicinal uses of, 529–530, 532 narcotic pain killers, 529–530, 532 nicotine, 527 quinine, 529 Alkalosis A body condition in which the pH of blood increases from its normal value of 7.4 to a value of 7.5, 279 metabolic, 279 respiratory, 279 Alkane A saturated hydrocarbon in which the carbon atom arrangement is acyclic, 323 branched-chain, 326–327 chemical reactions of, 347–350 combustion of, 347, 349 conformations of, 327–329 continuous-chain, 326 general molecular formula for, 323 halogenation of, 347–350 isomerism for, 326–329 IUPAC nomenclature for, 329–335 line-angle structural formulas for, 335–337 natural sources of, 344–345 physical properties of, 346–347 physical-state summary for, 347 physiological effects of, 348 structural formulas for, 324–326 three-dimensional structural representations for, 323–324 Alkene An acyclic unsaturated hydrocarbon that contains one or more carbon–carbon double bonds, 362 addition reactions and, 373–378 chemical-reaction summary for, 383 cis–trans isomers for, 368–370 constitutional isomerism for, 366–368 functional group for, 362 general molecular formula for, 362 halogenation, 375 hydration, 375, 410 hydrogenation, 374–375 hydrohalogenation, 375–376 line-angle structural formulas for, 365–366 naturally occurring, 370–372 nomenclature for, 363–365 physical properties of, 373 physical-state summary for, 373 preparation of, from alcohols, 411–415 Alkenyl group A noncyclic hydrocarbon substituent in which a carbon–carbon double bond is present, 365 Alkoxy group An —OR group, an alkyl (or aryl) group attached to an oxygen atom, 423 Alkyl group The group of atoms that would be obtained by removing a hydrogen atom from an alkane, 330 branched chain, 339–340

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Index/Glossary

branched, naming of, 339–340 continuous-chain, 330 unbranched, naming of, 339–340 Alkyl halide amine preparation using, 523–524 nomenclature using concept of, 350–351 preparation of, from alcohols, 417–418 Alkylation, aromatic hydrocarbons, 390 Alkyne An acyclic unsaturated hydrocarbon that contains one or more carbon–carbon triple bonds, 382 chemical reactions of, 383–384 functional group for, 382 general molecular formula for, 382 line-angle structural formulas for, 383 nomenclature for, 382–383 physical properties of, 383 physical-state summary for, 383 Allosteric enzyme An enzyme with two or more protein chains (quaternary structure) and two kinds of binding sites (substrate and regulator), 713 characteristics of, 713 Alpha helix structure A secondary protein structure in which a single protein chain adopts a shape that resembles a coiled spring (helix), with the coil configuration maintained by hydrogen bonds, 672 amount of, in proteins, 672–674 Alpha particle A particle in which two protons and two neutrons are present that is emitted by certain radioactive nuclei, 294 characterization of, 294 emission of, equations for, 295 notation for, 294 nuclear medicine and, 312 penetrating ability of, 305 Alpha particle decay The radioactive decay process in which an alpha particle is emitted from an unstable nucleus, 295 equations for, 295–297 ion pair formation and, 305 Alternative splicing A process by which several different proteins that are variations of a basic structural motif can be produced from a single gene, 752 heterogeneous nuclear RNA and, 752 protein formation and, 752 Aluminum, corrosion of, 232 Amide A carboxylic acid derivative in which the carboxyl —OH group has been replaced with an amino or a substituted amino group, 532 aromatic, 533 chemical reaction summary for, 543 classifications of, 532 cyclic, 533 functional group for, 532 generalized formula for, 532 hydrogen bonding and, 536–537 hydrolysis of, 540–541 IUPAC-common name contrast for, 534 line-angle structural formulas for, 533 local anesthetics use, 536 nomeclature for, 533–535 physical properties of, 536–537 physical-state summary for, 536

preparation of, from carboxylic acids, 537–538 primary, 532–533 saponification of, 540–541 secondary, 532–533 tertiary, 532–533 Amidification reaction The reaction of a carboxylic acid with an amine (or ammonia) to produce an amide, 538 examples of, 538–540 Amine An organic derivative of ammonia (NH3) in which one or more alkyl, cycloalkyl, or aryl groups are attached to the nitrogen atom, 515 aromatic, 517–518 basicity of, 519–520 biochemically important, selected, 526–529 chemical reaction summary for, 543 classifications of, 515–516 cyclic, 516 deprotonated form of, 523 free, 523 free base form of, 523 functional group for, 515 generalized formula for, 515 heterocyclic, 525 hydrogen bonding and, 519 IUPAC-common names contrast for, 518 line-angle structural formulas for, 516 neurotransmitter function for, 526–528 nomenclature for, 516–518 physical properties of, 519 physical-state summary for, 519 preparation of, with alkyl halides, 523–524 primary, 515–516 protonated form of, 523 secondary, 515–516 tertiary, 515–516 Amine salt An ionic compound in which the positive ion is a mono-, di- or trisubstituted ammonium ion and the negative ion comes from an acid, 521 nomenclature of, 521–523 preparation of, with acids, 521–522 reaction with bases, 522–523 uses for, 522 Amino acid An organic compound that contains both an amino (—NH2) group and a carboxyl (—COOH) group, 656 acid–base properties of, 659–661 alpha, 656–657 carbon skeletons, degradation products from, 888, 890 carbon skeletons, degradation sequences for, 888, 890 chirality of, 658–659 codons for, 753–754 degradation of, stages in, 878–879 essential, 658, 878 Fischer projection formula and, 658–659 glucogenic, 890 isoelectric point for, 661 ketogenic, 890 nonessential, biosynthesis of, 891–892 nonessential, listing of, 878 nonpolar, 656–657 nonstandard, urea cycle and, 884

A-29

oxidative deamination and, 882–883 peptide formation from, 663–666 polar acidic, 656–657 polar basic, 656–657 polar neutral, 656–657 separation of, using electrophoresis, 661–663 standard, names and abbreviations for, 657 standard, structures of, 657 structural characteristics of, 656–657 sulfur-containing, sulfuric acid from, 888 transamination and, 879–882 utilization of, 877–878 a-Amino acid An amino acid in which the amino group and the carboxyl group are attached to the alpha carbon atom, 656 structural characteristics of, 656 Amino acid pool The total supply of free amino acids available for use within the human body, 877 sources contributing to, 877 utilization of amino acids in, 877 Amino acid residue The portion of an amino acid structure that remains, after the release of H2O, when an amino acid participates in peptide bond formation as it becomes part of a peptide chain, 665 Amino group The —NH2 functional group, 515 Amino sugar, 581–582 Ammonia amide preparation and, 537–538 amine preparation and, 523–524 weak base, 259 Ammonium ion carbamoyl phosphate formation and, 884 oxidative deamination reactions and, 882–883 toxicity of, biochemical systems and, 883 AMP. See Adenosine monophosphate Amphiprotic substance A substance that can either lose or accept a proton and thus can function as either a Brønsted–Lowry acid or a Brønsted–Lowry base, 257 Brønsted–Lowry theory and, 256–257 examples of, 257 Amylopectin, 591–592 Amylose, 591 Anabolism All metabolic reactions in which small biochemical molecules are joined together to form larger ones, 777 Anaerobic process ethanol fermentation, 824 glycolysis, 813 lactate fermentation, 823–824 oxygen conditions for, 823 Androgens biochemical functions of, 642 preparation of, from cholesterol, 869 Anesthetics, ethers as, 425 Aniline, 517 Anisole, 424 Antacid, 265 Antibiotic A substance that kills bacteria or inhibits their growth, 715 Cipro, 717–718 doxycycline, 718

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Index/Glossary

Antibiotic (Continued) macrolide, 493 penicillins, 716–717 protein synthesis inhibition and, 761 sulfa drugs, 715–716 Antibody A biochemical molecule that counteracts a specific antigen, 687 immunoglobulin response to, 687–689 Anticodon A three-nucleotide sequence on a tRNA molecule that is complementary to a codon on a mRNA molecule, 756 codon interaction with, 757–758 tertiary RNA and, 756–758 Antigen A foreign substance, such as a bacterium or virus, that invades the human body, 687 Antihistamine, counteracting effects of histamines, 529 Anti-inflammatory drug aspirin, 646 Celebrex, 646 ibuprofen, 646 naproxen, 646 nonsteroidal, 646 steroidal, 646 Vioxx, 646 Antimicrobials, carboxylic acid salt use as, 486 Antioxidant A substance that protects other substances from being oxidized by being oxidized itself in preference to the other substances, 421 bilirubin, 894 flavonoids, 805 peptide, 668 phenols, 421–422 rancidity and, 627 reactive oxygen species and, 805 vitamin C, 721 vitamin E, 728 Antiseptic, phenols, 421 Apoenzyme The protein part of a conjugated enzyme, 699 Aqueous solution A solution in which water is the solvent, 195 Arginine nitric oxide production and, 889 structure of, 884 urea cycle and, 884–887 Argininosuccinate, urea cycle and, 885–887 Aromatic hydrocarbon An unsaturated cyclic hydrocarbon that does not readily undergo addition reactions, 384 alkylation, 390 bonding analysis for, 385–386 functional group for, 386 fused-ring, 390–391 halogenation, 390 nomenclature for, 386–389 physical properties of, 389 sources for, 389 Aromatic ring system A highly unsaturated carbon ring system in which both localized and delocalized bonds are present, 386 Arrhenius, Svante August, 253 Arrhenius acid A hydrogen-containing compound that, in water, produces hydrogen ions (H⫹ ions), 253

characteristics of, 253–254 ionization of, 254 Arrhenius base A hydroxide-containing compound that, in water, produces hydroxide ions (OH⫺ ions), 253 characteristics of, 253–254 dissociation of, 254 Artificial sweeteners, 590 Aryl group An aromatic carbon ring system from which one hydrogen atom has been removed, 419 Aspartame, 590 Aspartate, urea cycle and, 885–887 Aspartate transaminase (AST), 719 Aspirin mode of action, 646 pharmacology of, 494 structure of, 492–493 Atmosphere, pressure unit of, 168 Atom The smallest particle of an element that can exist and still have the properties of the element, 12 atomic number for, 53–54 building block for matter, 12–13 charge neutrality and, 52 chemical properties of, electrons and, 54 electron configurations for, 68–71 internal structure of, subatomic particles and, 52 formation from, 87–90 isoelectronic species and, 90 limit of chemical subdivision and, 13 mass number for, 53–54 nucleus of, 52 orbital diagrams for, 68–71 relative mass scale for, 56 size of, 12–13 subatomic particle relationships for, 52 Atomic mass The calculated average mass for the isotopes of an element expressed on a scale where 12C serves as the reference point, 56 amu unit for, 56 calculation of, procedure for, 56–57 relative mass scale for, 56 values for, listing of, inside front cover, weighted-average concept and, 56 Atomic mass unit relationship to grams unit, 142 relative scale for, 56 Atomic number The number of protons in the nucleus of an atom, 53 electrons and, 53 element identification and, 54 for elements, listing of, inside front cover informational value of, 53 protons and, 53 use of, with chemical symbols, 54 Atomic structure, subatomic particles and, summary diagram for, 58 Atorvastatin, cholesterol levels and, 867 ATP. See Adenosine triphosphate Atropine, 529 Avogadro, Amedeo, 139–140 Avogadro’s number The name given to the numerical value 6.02 ⫻ 10 23, 139 conversion factors based on, 139

magnitude of, examples illustrating, 139 use of, in calculations, 139–140 Background radiation Radiation which comes from natural sources to which living organisms are exposed on a continuing basis, 308 sources of, 308 Bacteria, helicobacter pylori, 707 Balanced chemical equation A chemical equation that has the same number of atoms of each element involved in the reaction on both sides of the equation, 147 coefficients and, 147 guidelines for balancing, 146–149 law of conservation of mass and, 147 Balanced nuclear equation A nuclear equation in which the sums of the subscripts (atomic numbers or particle charges) on both sides of the equation are equal, and the sums of the superscripts (mass numbers) on both sides of the equation are equal, 295 examples of, 295–297 rules for balancing, 295 Barbiturates, 536 Barometer A device used to measure atmospheric pressure, 168 Base Arrhenius, 253–254 Brønsted–Lowry, 254–257 neutralization of, 262–263 strengths of, 259 strong, 259 weak, 259 Base ionization constant (Kb) The equilibrium constant for the reaction of a weak base with water, 261 mathematical expression for, 261 Base pairing complementary nature of, 742–744 DNA double helix and, 742–744 Base-stacking interactions DNA structure and, 744 Basic solution An aqueous solution in which the concentration of OH⫺ ion is higher than that of H3O⫹ ion; an aqueous solution whose pH is greater than 7.0, 264, 268 hydronium ion concentration and, 264–266 pH value and, 268 Becquerel, Antoine Henri, 293 Benedict’s test aldehyde oxidation and, 455–457 monosaccharides and, 578 polysaccharides and, 590 reducing sugars and, 578 Benzaldehyde, 447 Benzamide, 533 Benzene bonding in, 385–386 properties of, 389–390 Benzoic acid derivatives, antimicrobial action of, 486 structure of, 476 Beta oxidation pathway The metabolic pathway that degrades fatty acids, by removing two carbon atoms at a time, to acetyl CoA with FADH2 and NADH also being produced, 847

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Index/Glossary

acetyl CoA production and, 847–849 ATP production from, 851–852 contrasted with lipogenesis, 858–859 FADH2 production and, 847–849 NADH production and, 847–849 steps in, 847–849 summary-diagram for, 848 unsaturated fatty acids and, 851 Beta particle A particle whose charge and mass are identical to those of an electron that is emitted by certain radioactive nuclei, 294 characterization of, 294 emission of, equations for, 295–296 formation of, within nucleus, 296 ion pair formation and, 305 notation for, 294 nuclear medicine and, 312 penetrating ability of, 305–279 Beta particle decay The radioactive decay process in which a beta particle is emitted from an unstable nucleus, 295 equations for, 295–297 Beta pleated sheet structure A secondary protein structure in which two fully extended protein chain segments in the same or different molecules are held together by hydrogen bonds, 672–673 types of, 673 BHA, 421 BHT, 421 Bile A fluid containing emulsifying agents that is secreted by the liver, stored in the gallbladder, and released into the small intestine during digestion, 641 chemical composition of, 641 lipid digestion and, 843 Bile acid A cholesterol derivative that functions as a lipid-emulsifying agent in the aqueous environment of the digestive tract, 640 biochemical functions of, 640–641 glycocholic acid, 641 structural characteristics of, 640–641 taurocholic acid, 641 Bile pigment A colored tetrapyrrole degradation product present in bile, 895 coloration of, 895–896 hemoglobin catabolism and, 895–896 stercobilin, 894–895 urobilin, 894–895 Bilirubin antioxidant properties of, 894 hemoglobin catabolism and, 893–894 jaundice and, 895–896 structure of, 893 Bilirubin diglucuronide hemoglobin catabolism and, 894 structure of, 894 Biliverdin hemoglobin catabolism and, 892–893 structure of, 893 Binary compound A compound in which only two elements are present, 94 ionic, naming of, 94–98 ionic, recognition of, 94 molecular, common names for, 130–131 molecular, naming of, 130–131

Binary ionic compound An ionic compound in which one element present is a metal and the other element present is a nonmetal, 94 rules for naming, 94–98 Binary molecular compound A molecular compound in which only two nonmetallic elements are present, 130 rules for naming, 130–131 Biochemical energy production acetyl group formation and, 788 citric acid cycle and, 788 digestion and, 788 electron transport chain and, 788 overview diagram for, 789 Biochemical substance A chemical substance found within a living organism, 556 bioinorganic, 556 bioorganic, 556 types of, 556 Biochemistry The study of the chemical substances found in living organisms and the chemical interactions of these substances with each other, 555 Biological wax A lipid that is a monoester of a long-chain fatty acid and a long-chain alcohol, 646 biochemcal functions of, 646–647 contrasted with mineral wax, 646–647 generalized structure of, 646 Biotechnology, 765–768 Biotin coenzyme functions of, 724 dietary sources of, 725 structure of, 723 1,3-Bisphosphoglycerate glycolysis and, 817–818 Blood buffer systems within, 279 lipoproteins and, 690–691 pH change and acidosis, 279 pH change and alkalosis, 279 types, frequency statistics for, 580 types, monosaccharide markers and, 580 Blood plasma electrolyte composition of, 281, 283 pH of, salt hydrolysis and, 274 Blood pressure high, factors that reduce, 178 measurement of, 178 normal range for, 178 sodium ion/potassium ion ratio and, 178 Boiling A form of evaporation where conversion from the liquid state to the vapor state occurs within the body of the liquid through bubble formation, 180 bubble formation and, 180 Boiling point The temperature at which the vapor pressure of a liquid becomes equal to the external (atmospheric) pressure exerted on the liquid, 180 elevation of, solutes and, 209–210 factors affecting magnitude of, 180 normal, 180 table of, at various pressures for water, 180–181 Bombardment reaction A nuclear reaction brought about by bombarding stable

A-31

nuclei with small particles traveling at very high speeds, 300 equations for, 300–301 synthetic elements and, 301 Bond polarity A measure of the degree of inequality in the sharing of electrons between two atoms in a chemical bond, 125 electronegativity and, 125–126 electronegativity differences and, 125–126 notations for, 125 types of chemical bonds and, 124–126 Bonding electrons Pairs of valence electrons that are shared between atoms in a covalent bond, 110 Boyle, Robert, 168–169 Boyle’s law The volume of a fixed amount of a gas is inversely proportional to the pressure applied to the gas if the temperature is kept constant, 168 kinetic molecular theory and, 169 mathematical form of, 168 use of, in calculations, 169 Branched-chain alkane An alkane in which one or more branches (of carbon atoms) are attached to a continuous chain of carbon atoms, 326 Brønsted, Johannes Nicolaus, 254 Brønsted–Lowry acid A substance that can donate a proton (H⫹ ion) to some other substance, 254 characteristics of, 254–257 conjugate bases of, 255–256 Brønsted–Lowry base A substance that can accept a proton (H⫹ ion) from some other substance, 254 characteristics of, 254–257 conjugate acids of, 255–256 Brown fat heat generation and, 803 thermogenin and, 803 Buffer An aqueous solution containing substances that prevent major changes in solution pH when small amounts of acid or base are added it, 274 chemical composition of, 274–275 Henderson–Hasselbalch equation, calculations for, 277–278 mode of action of, 275–276 pH change for, 275–277 summary diagram for, 278 Butyryl ACP lipogenesis and, 862 CAC. See Citric acid cycle Caffeine pharmacology of, 526 structure of, 526 Calorie The amount of heat energy needed to raise the temperature of 1 gram of water by 1 degree Celsius, 43 dietetic, 43 relationship to joule, 43 Cancer, fused-ring aromatic hydrocarbons and, 391 Carbamoyl phosphate structure of, 884 urea cycle and, 884–885

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Index/Glossary

Carbohydrate A polyhydroxy aldehyde, a polyhydroxy ketone, or a compound that yields polyhydroxy aldehydes or polyhydroxy ketones upon hydrolysis, 557 classifications of, 557 complex, 597–598 components of cell membranes, 639 functions of, in humans, 556 occurrence of, 556 photosynthesis and, 556 simple, 597–598 Carbohydrate digestion breakdown products from, 812 enzymes needed for, 811–813 fructose from, 812 galactose from, 812 glucose from, 812 location for, within human body, 811–812 Carbohydrate metabolism Cori cycle and, 832 fates of pyruvate in, 822–826 gluconeogenesis and, 830–832 glycogenesis and, 828–829 glycogenolysis and, 829 glycolysis and, 813–821 hormonal control of, 835–837 pentose phosphate pathway and, 833–834 relationship between lipid metabolism and, 868–869, 895–897 relationship between protein metabolism and, 895–897 Carbon atom bonding characteristics of, 322 classifications of, 338–339 primary, 338 quaternary, 339 saturated, 400 secondary, 338 tertiary, 339 Carbon dioxide atmospheric concentrations of, 227 carbamoyl phosphate formation and, 884 citric acid cycle production of, 791, 793 ethanol fermentation and, 824 global warming and, 227 pentose phosphate pathway and, 834 pyruvate oxidation and, 824 solubility of, in water, 195 Carbon monoxide carboxyhemoglobin formation and, 153–154 concentration of, air pollution and, 153–154 health effects of, 153–154 hemoglobin catabolism and, 893 production of, cigarette smoking and, 153–154 properties of, 3 steel-making and, 3 toxicity of, 3 Carbonyl group A carbon atom double bonded to an oxygen atom, 442 aldehydes and, 443 amides and, 444 bond angles within, 442 carboxylic acids and, 443 compounds containing, major classes of, 443–444 esters and, 443–444

ketones and, 443 polarity of, 442 sulfur-containing, 464 Carboxyhemoglobin, formation of, human body and, 153–154 Carboxyl group A carbonyl group (C"O) with a hydroxyl group (—OH) bonded to the carbonyl carbon atom, 473 notations for, 473 polarity of, 483 Carboxylate ion The negative ion produced when a carboxylic acid loses one or more acidic hydrogen atoms, 484 charge on, 484 nomenclature for, 484 Carboxylic acid An organic compound whose functional group is the carboxyl group, 473 acidity of, 484 aromatic, 476 chemical reaction summary for, 498 dicarboxylic, 476–479 ester synthesis from, 487–488 generalized formula for, 474 hydrogen bonding and, 483 hydroxy, 479–481 IUPAC-common name contrast for, 478 keto, 481 line-angle structural formulas for, 475 metabolic, 482–483 monocarboxylic, 474–477 nomenclature for, 474–479 physical properties of, 483 physical-state summary for, 483 polyfunctional, 479–483 preparation of, from alcohols, 415–417, 483 preparation of, from aldehydes, 483 reactions of, with alcohols, 487–488 salts of, 484–486 strength of, 484 unsaturated, 479 Carboxylic acid derivative An organic compound that can be synthesized from or converted into a carboxylic acid, 474 types of, 474 Carboxylic acid salt An ionic compound in which the negative ion is a carboxylate ion, 485 formation of, 484–485 nomenclature of, 485 reaction of, with acids, 485–486 solubilities of, 486 uses for, 486 Carnitine, shuttle system participant, 847 b-Carotene color and, 374 terpene structure of, 372 vitamin A and, 726 Carotenoids, color and, 374 Carvone, 451 Catabolism All metabolic reactions in which large biochemical molecules are broken down to smaller ones, 777 Catalyst A substance that increases a chemical reaction rate without being consumed in the reaction, 236 activation energy and, 236–237

equilibrium position and, 246 reaction rates and. 236–237 Catalytic protein, 682 Catechol, 420 Celebrex, 646 Cell adipocyte, 845 cytoplasm of, 779 cytosol of, 779 eukaryotic, characteristics of, 779–780 organelles and, 779 prokaryotic, characteristics of, 779 Cell membrane A lipid-based structure that separates a cell’s aqueous-based interior from the aqueous environment surrounding the cell, 637 active transport and, 639–640 bilayer structure of, 637–638 bonding interactions within, 637–638 carbohydrate components of, 639 facilitated transport and, 639–640 lipid components of, 637–638 passive transport and, 639–640 protein components of, 638–639 Cellobiose hydrolysis of, 584 occurrence of, 584 structure of 584 Cellulose dietary fiber and, 594 properties of, 593–594 structure of, 593 Cephalins, 632 Cerebrosides, 635 Change chemical, 4–5 in matter, examples of, 4–5 physical, 4–5 Change of state A process in which a substance is changed from one physical state to another physical state, 176 endothermic, 176–177 exothermic, 176–177 summary diagram of, 176 Charles, Jacques, 170–171 Charles’s law The volume of a fixed amount of gas is directly proportional to its Kelvin temperature if the pressure is kept constant, 170 kinetic molecular theory and, 171 mathematical form of, 170 use of, in calculations, 170–171 Chemical, use of the term, 5–6 Chemical bond The attractive force that holds two atoms together in a more complex unit, 84 conjugated, 374 coordinate covalent, 113–114 covalent bond model for, 84, 108–109 delocalized, 386 double covalent, 111–112 ionic bond model for, 87–89 phosphoanhydride, 781 polarity of, 124–126 single covalent, 111–112 strained, 786–787 strained, adenosine phosphates and, 782

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Index/Glossary

triple covalent, 112 types of, 84 Chemical change A process in which a substance undergoes a change in chemical composition, 4 characteristics of, 4–5 control of, 5 Chemical equation A written statement that uses chemical symbols and chemical formulas instead of words to describe the changes that occur in a chemical reaction, 146 calculations based on, 151–155 conventions used in writing, 146 general calculations involving, 151–155 macroscopic level interpretation of, 150 microscropic level interpretation of, 150 molar interpretation of, 150–151 mole concept and, 150–151 procedures for balancing, 147–149 special symbols used in, 150 Chemical equilibrium A state in which forward and reverse chemical reactions occur simultaneously at the same rate, 237 conditions necessary for, 237–238 contrasted with physical equilibrium, 237 equilibrium constants and, 239–243 Le Châtelier’s principle and, 243–246 position of, 242–243 Chemical formula A notation made up of the chemical symbols of the elements present in a compound and numerical subscripts (located to the right of each chemical symbol) that indicate the number of atoms of each element present in a molecule of the compound, 15 general calculations involving, 143–146 interpreting, in terms of atoms, 15 macroscopic level interpretation of, 142 microscopic level interpretation of, 142 molar interpretation of, 142–143 parenthesis use and, 15 subscripts in, 15 Chemical property A characteristic of a substance that describes the way the substance undergoes or resists change to form a new substance, 2 conditions that affect, 3 determination of, electrons and, 54 examples of, 2–4 Chemical reaction A process in which at least one new substance is produced as a result of chemical change, 223 acyl transfer, 503 addition, 224, 373–378 alcohol dehydration, 411–415 aldehydes and ketones, summary for, 462 alkene hydration, 410 alkylation, 390 amidification, 538–540 combination, 223–224 combustion, 225–226, 347, 349 completeness of, 242–243 contrasted with nuclear reaction, 316 coupled, 800–801 decomposition, 224 double-replacement, 225 elimination, 224, 412

endothermic, 234–235 equilibrium constants for, 239–243 ester, 495–497 esterification, 487–488 exothermic, 234–235 halogenation, 347–350, 375, 390 hydration, 376 hydrogenation, 374–375 hydrohalogenation, 375–376 nonredox, 226, 230 oxidation–reduction, 226–232 oxidative deamination, 882 polymerization, addition, 378–379 polymerization, condensation, 499–500, 542–544 protein, 683–684 redox, 226–232 reversible, 238–239 salt hydrolysis, 273–274 saponification, 496–497 single-replacement, 224–225 substitution, 225, 347–349 transamination, 879 Chemical reaction rate The rate at which reactants are consumed or products produced in a given time period in a chemical reaction, 235 catalysts and, 236–237 concentration change and, 235–236 factors affecting, 235–237 rate of, factors affecting, 235–237 physical nature of reactants and, 235 temperature change and, 236 Chemical stoichiometry, 151 Chemical subdivision limit of, 13 Chemical symbol A one- or two-letter designation for an element derived from the element’s name, 11 capitalization rules for, 11 complete notation form of, 54 generalizations concerning, 11 listing of, 12 subscript and superscript use with, 54 Chemiosmotic coupling An explanation for the coupling of ATP synthesis with electron transport chain reactions that requires a proton gradient across the inner mitochondrial membrane, 801 concepts involved in, 801–802 electrochemical gradient and, 801–802 Chemistry The field of study concerned with the characteristics, composition, and transformations of matter, 1 scope of, 1 Chiral center An atom in a molecule that has four different groups tetrahedrally bonded to it, 558 identification of, in molecules, 558–560 Chiral molecule A molecule whose mirror images are not superimposable, 558 examples of, 558–560 interactions between, 568 Chirality amino acid, 658–659 Fischer projection formulas and, 561–565 monosaccharides and, 559–560

A-33

Chitin properties of, 594 structure of, 594 Chlorofluorocarbons global warming and, 227 ozone layer and, 351 Chocolate caffeine content of, 531 theobromine content of, 531 types of, 531 Cholecalciferol, 726–727 Cholesterol A C27 steroid molecule that is a component of cell membranes and a precursor for other steroid-based lipids, 635 amounts of, various foods and, 637 biochemical functions of, 636 biosynthesis of, 864–868 blood levels of, statins and, 867 blood levels of, “trans” fatty acids, 626 cell membrane component, 638–639 HDL and LDL and, 636 human body levels of, 636 inhibition of biosynthesis of, 867 structure of, 635–636 Cholesterol derivative bile acids, 640–641 steroid hormones, 641–643 vitamin D, 726–727 Chromosome An individual DNA molecule bound to a group of proteins, 746 general characteristics of, 746–747 protein content of, 746 Chylomicron A lipoprotein that transports triacylglycerols from intestinal cells, via the lymphatic system, to the bloodstream, 843 lipid digestion and, 843–844 Chyme lipid digestion and, 842–843 physical characteristics of, 842–843 Cinnamaldehyde, 451 Cipro mode of action, 717–718 Cis- A prefix that means “on the same side,” 343 meaning of, 343 Cis–trans isomers Isomers that have the same molecular and structural formulas but different arrangements of atoms in space because of restricted rotation about bonds, 343 alkenes, 368–370 cycloalkanes, 343–344 limitations of use of concept, 344 vision and, 371 Citrate citric acid cycle and, 789–790, 794 Citric acid, 480–483 Citric acid cycle (CAC) The series of biochemical reactions in which the acetyl portion of acetyl CoA is oxidized to carbon dioxide and the reduced coenzymes FADH2 and NADH are produced, 788 acetyl CoA and, 789–790 carbon dioxide production and, 791, 793 FADH2 production from, 792–793 important features of, 792–793 intermediates, relationship to lipogenesis intermediates, 864

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Index/Glossary

Citric acid cycle (CAC) (Continued) linkage to urea cycle, 888 NADH production from, 791–793 overall equation for, 792 reactions of, 789–792 regulation of, 793 Citrulline nitric oxide production and, 889 structure of, 884 urea cycle and, 884–887 Clones Cells with identical DNA that have descended from a single cell, 767 recombinant DNA production and, 767–768 CoA-SH. See Coenzyme A Codeine derivatives of, 530, 532 structure of, 530, 532 Codon A three-nucleotide sequence in a mRNA molecule that codes for a specific amino acid, 753 amino acids and, 753–754 anticodon interaction with, 757–758 characteristics of, 753–754 listing of, 754 messenger RNA and, 754–756 Coenzyme An organic molecule that serves as a cofactor in a conjugated enzyme, 699 vitamin B derivatives as, 722–723 Coenzyme A general metabolic function of, 785 generalized structure of, 784–785 structural subunits within, 784–785 Coenzyme Q electron transport chain and, 796–798 structural characteristics of, 796 Coenzyme Q-cytochrome c reductase electron transport chain and, 797–798 structural characteristics of, 797–798 Cofactor The nonprotein part of a conjugated enzyme, 699 Cohesive forces, potential energy and, 164–166 Collagen biochemical function of, 680–681 gelatin from, 687 nonstandard amino acids and, 687 structural characteristics of, 680–681 Colligative property A physical property of a solution that depends only on the number (concentration) of solute particles (molecules or ions) present in a given quantity of solvent and not on their chemical identities, 209 boiling point elevation as, 209–210 freezing point depression as, 210 osmotic pressure as, 211–212 summary diagram for, 215 vapor pressure depression as, 209 Collision theory A set of statements that give the conditions necessary for a chemical reaction to occur, 233 activation energy and, 233 collision orientation and, 234 concepts involved in, 233–234 molecular collisions and, 233 Colloidal dispersion A homogeneous mixture that contains dispersed particles that are intermediate in size between those of a

true solution and those of an ordinary heterogeneous mixture, 208 characteristics of, 208–209 terminology associated with, 208 Tyndall effect and, 208 Colostrum, immunoglobin content of, 689 Combination reaction A chemical reaction in which a single product is produced from two (or more) reactants, 223 examples of, 224 general equation for, 223, 226 Combined gas law The product of the pressure and volume of a fixed amount of gas is directly proportional to its Kelvin temperature, 172 mathematical form of, 172 use of, in calculations, 172 Combustion reaction A chemical reaction between a substance and oxygen (usually from air) that proceeds with the evolution of heat and light (usually from a flame), 225, 347 alcohol, 411 alkane, 347 cycloalkane, 350 examples of, 225–226 global warming and, 227 Common metabolic pathway The sum total of the biochemical reactions of the citric acid cycle, the electron transport chain, and oxidative phosphorylation, 788 ATP production from, 802–804 citric acid cycle and, 788–794 electron transport chain and, 794–800 oxidative phosphorylation and, 800–804 summary diagram for, 802 Competitive enzyme inhibitor A molecule that sufficiently resembles an enzyme substrate in shape and charge distribution that it can compete with the substrate for occupancy of the enzyme’s active site, 710 mode of action, 710–712 Complementary bases Pairs of bases in a nucleic acid structure that can hydrogenbond to each other, 743 structural characteristics of, 743–744 Complementary DNA strands Strands of DNA in a double helix with base pairing such that each base is located opposite its complementary base, 743 Complete dietary protein A protein that contains all the essential amino acids in the same relative amounts in which the human body needs them, 658 Complex carbohydrate A dietary polysaccharide, 597 Compound A pure substance that can be broken down into two or more simpler pure substances by chemical means, 7 binary, 94 characteristics of, 7–9 classification of, for naming purposes, 130 comparison with mixtures, 8 dextrorotatory, 567 formula mass of, 137–138 heteroatomic molecules and, 13–14 high-energy, 786–788

inorganic, contrasted with organic, 321–322 levorotatory, 567 molar mass of, 140–141 number of known, 7 optically active, 567–568 organic, contrasted with inorganic, 321–322 types of, 83–84 Compressibility A measure of the change in volume in a sample of matter resulting from a pressure change, 163 states of matter and, 163–164 Concentrated solution A solution that contains a large amount of solute relative to the amount that could dissolve, 195 Concentration The amount of solute present in a specified amount of solution, 198 units for, 198–205 Concentration units mass–volume percent, 200–201 molarity, 203–205 percent by mass, 198–200 percent by volume, 200 Condensation process of, 176–177 Condensation polymer A polymer formed by reacting difunctional monomers to give a polymer and some small molecule (such as water) as a by-product of the process, 499 diacid–dialcohol, 499–500 diacid–diamine, 542 polyamides, 542–544 polyesters, 499–500 polyurethanes, 544–545 Condensation reaction A chemical reaction in which two molecules combine to form a larger one while liberating a small molecule, usually water, 414 acetal formation, 460 amidification, 538 esterification, 487–488 intermolecular alcohol dehydration, 413–414 lipogenesis and, 861 polyamide formation, 542 polyester formation, 499–500 Condensed structural formula A structural formula that uses groupings of atoms, in which central atoms and the atoms connected to them are written as a group, to convey molecular structural information, 324 examples of, 324 interpretation guidelines for, 325 Conformation The specific three-dimensional arrangement of atoms in an organic molecule at a given instant that results from rotations about carbon-carbon single bonds, 327 alkane, 327–329 Conjugate acid The species formed when a proton (H⫹ ion) is added to a Brønsted– Lowry base, 256 Brønsted–Lowry theory and, 255–257 relationship to conjugate bases, 256 Conjugate acid–base pair Two substances, one an acid and one a base, that differ from each other through the loss or gain of a proton (H⫹ ion), 256

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Index/Glossary

Brønsted–Lowry theory and, 255–257 determining members of, 256 Conjugate base The species formed that remains when a proton (H⫹ ion) is removed from a Brønsted–Lowry acid, 256 Brønsted–Lowry theory and, 255–257 relationship to conjugate acids, 256 Conjugated double bonds, color and, 374 Conjugated enzyme An enzyme that has a nonprotein part in addition to a protein part, 699 Conjugated protein A protein in which one or more other components in addition to amino acids are present, 669 types of, 669 Constitutional isomers Isomers that differ in the connectivity of atoms, that is, in the order atoms are attached to each other within molecules, 327 alkane, determining structural formulas for, 334–335 alkane, number possible, 327 alkene, determination of, 367–368 positional, 366 skeletal, 367 Continuous-chain alkane An alkane in which all carbon atoms are connected in a continuous nonbranching chain, 326 Contractile protein, 683 Conversion factor A ratio that specifies how one unit of measurement is related to another unit of measurement, 34 Avogadro’s number, use of in, 139, 143–146 characteristics of, 34 density, use of as a, 41 English–English, 35 equation coefficients, use of in, 150 formula subscripts, use of in, 142–143 mass–volume percent, use of as a, 202–203 metric–English, listing of, 36 metric–metric, 35 molar mass, use of in, 141, 143–146 molarity, use of as a, 204–205 percent by mass, use of as a, 200–201 percent by volume, use of as a, 202 significant figures and, 35 use of, in dimensional analysis, 36–38 Coordinate covalent bond A covalent bond in which both electrons of a shared pair come from one of the two atoms involved in the bond, 113 general characteristics of, 114 molecules containing, examples of, 113–114 Copolymer A polymer in which two different monomers are present, 382 Saran, 381–382 styrene-butadiene rubber, 382 Copper, corrosion of, 232 CoQ. See Coenzyme Q Cori, Carl, 832 Cori, Gerty Radnitz, 832 Cori cycle A cyclic biochemical process in which glucose is converted to lactate in muscle tissue, the lactate is reconverted to glucose in the liver, and the glucose is returned to the muscle tissue, 832 steps in, 832

Corn syrup, high fructose, 588 Corrosion aluminum and, 232 copper and, 232 gold and, 232 iron and, 232 metallic, redox reactions for, 232 silver and, 232 Cortisol, 643 Cortisone, 643 Coupled reactions Pairs of biochemical reactions that occur concurrently in which energy released by one reaction is used in the other reaction, 800 Covalent bond A chemical bond formed through the sharing of one or more pairs of electrons between two atoms; a chemical bond resulting from two nuclei attracting the same shared electrons, 84, 109 contrasted with ionic bond, 108–109 coordinate, 113–114 double, 111–112 Lewis structures and, 109–111 multiple, 112 nonpolar, 124–126 octet rule and, 109–111 polar, 124–126 simplest example of, 109 single, 111–112 triple, 112 types of, summary diagram, 127 valence electrons and number formed, 112–113 Covalent modification A process in which enzyme activity is altered by covalently modifying the structure of the enzyme through attachment of a chemical group to or removal of a chemical group from a particular amino acid within the enzyme’s structure, 715 dephosphorylation and, 715 phosphorylation and, 715 COX enzyme, 646 Creatine phosphokinase (CPK), 719 Crenation, hypotonic solutions and, 213–214 Cresols, 420 Crotonyl ACP, lipogenesis and, 862 Curie, Marie, 293–294 Curie, Pierre, 293 Cyanide poisoning electron transport chain and, 801 Cycloalkane A saturated hydrocarbon in which carbon atoms connected to one another in a cyclic (ring) arrangement are present, 340 chemical reactions of, 350 cis–trans isomers for, 343–344 combustion of, 350 general formula for, 340 halogenation of, 350 line-angle structural formulas for, 340–341 natural sources of, 344–345 nomenclature for, 341–342 physical properties of, 346–347 physical-state summary for, 347 Cycloalkene A cyclic unsaturated hydrocarbon that contains one or more carbon-carbon double bonds within the ring system, 362 general molecular formula for, 362

A-35

line-angle structural formulas for, 362 nomenclature for, 363–365 physical properties of, 373 physical-state summary for, 373 Cyclooxygenase anti-inflammatory drugs and, 646 forms of, 646 Cyclosporine, 688 Cysteine, disulfide bond formation and, 663 Cytochrome A heme-containing protein in which reversible oxidation and reduction of an iron atom occur, 797 electron transport chain and, 797–800 structural characteristics of, 797–798 Cytochrome c oxidase electron transport chain and, 798–799 structural characteristics of, 798–799 Cytoplasm The water-based material in a eukaryotic cell that lies between the nucleus and the outer membrane of the cell, 779 cytosol and, 779 organelles and, 779 Cytosine nucleotide subunit, 735, 737 structure of, 735, 737 Cytosol The water-based fluid part of the cytoplasm of a cell, 779 characteristics of, 779 Dalton, John, 173 Dalton’s law of partial pressures The total pressure exerted by a mixture of gases is the sum of the partial pressures of the individual gases present, 173–174 mathematical form of, 174 use of, in calculations, 174 Daughter nuclide The nuclide that is produced in a radioactive decay process, 295 Decomposition reaction A chemical reaction in which a single reactant is converted into two (or more) simpler substances (elements or compounds), 224 examples of, 224 general equation for, 224 Defense protein, 683 Dehydration reaction A chemical reaction in which the components of water (H and OH) are removed from a single reactant or from two reactants (H from one and OH from the other), 411–412 alcohols, 411–415 lipogenesis and, 862 Dehydrogenation reaction beta oxidation pathway and, 848 Delocalized bond A covalent bond in which electrons are shared among more than two atoms, 386 Demineralization tooth enamel and, 100 Denatured alcohol, 405 Density The ratio of the mass of an object to the volume occupied by that object, 39 human body, and percent body fat, 40 terminology associated with, 39 units for, 39 use of, as a conversion factor, 41 values, table of, 39

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A-36

Index/Glossary

Deoxyribonucleic acid (DNA) A nucleotide polymer in which each of the monomers contains deoxyribose, phosphate, and one of the heterocyclic bases adenine, cytosine, guanine, or uracil, 738–739 backbone of, structure for, 739 base-stacking interactions, 744 complementary strands of, 743–744 differences between RNA and, 747 double helix, base-pairing and, 742–744 double helix, general structure of, 741–744 mutations and base sequence for, 763 polymerase chain reaction and, 768–769 predicting base sequence, complementary strands and, 744 recombinant, 765–768 replication of, 745–746 sequencing of, 768–769 2-Deoxyribose nucleotide subunit, 735 occurrence of, 574 structure of, 574 Deposition, process of, 176–177 Desflurane, 425 Detergent, cleansing action of, 625 Deuterium, hydrogen isotope, 55 Dextrorotatory compound A chiral compound that rotates the plane of polarized light in a clockwise direction, 567 notation for, 567–568 Dextrose, 572 Diabetes glucose tolerance test for, 836 testing, aldehyde oxidation and, 456 testing, reducing sugars and, 578 type I, 836 type II, 836 Diacylglycerol, use of, as emulsifiers, 621 Dialysis The process in which a semipermeable membrane allows the passage of solvent, dissolved ions, and small molecules but blocks the passage of colloidalsized particles and large molecules, 216 artificial-kidney machines and, 216 relationship to osmosis, 215–216 Diastereomers Stereoisomers whose molecules are not mirror images of each other, 561 epimers and, 563 examples of, 561 Fischer projections formulas for, 561–565 recognizing, 562–565 Diatomic molecule A molecule that contains two atoms, 13 examples of, 13–14 Dicarboxylic acid A carboxylic acid that contains two carboxyl groups, one at each end of a carbon chain, 476 nomenclature for, 476–479 physical-state summary for, 483 Dietary fiber, cellulose as, 594 Digestion The biochemical process by which food molecules, through hydrolysis, are broken down into simpler chemical units that can be used by cells for their metabolic needs, 811 carbohydrates, 811–813

lipids, 842–844 proteins, 875–876 Dihydroxyacetone shuttle system participant, 826–827 structure of, 570–571 Dihydroxyacetone phosphate glycerol metabolism and, 846 glycolysis and, 816–817 Dilute solution A solution that contains a small amount of solute relative to the amount that could dissolve, 195 Dilution The process in which more solvent is added to a solution in order to lower its concentration, 205 mathematical equations associated with, 206–208 process of, 205–206 Dimensional analysis A general problemsolving method in which the units associated with numbers are used as a guide in setting up calculations, 36 metric–English conversions and, 37–38 metric–metric conversions and, 37 procedural steps in, 36–37 Dimethylsulfoxide (DMSO), uses for, 464 Dipole–dipole interaction An intermolecular force that occurs between polar molecules, 181 characteristics of, 181, 185 Diprotic acid An acid that supplies two protons (H⫹ ions) per molecule during an acid–base reaction, 257 examples of, 257 Direct deamination, 883 Disaccharide A carbohydrate that contains two monosaccharide units covalently bonded to each other, 557 examples of, biochemically important, 582–587 glycosidic linkage within, 582–587 reducing sugar, 583–587 Disinfectant, phenols, 421 Dispersed phase, colloidal dispersions and, 208 Dispersing medium, colloidal dispersions and, 208 Disruptive forces, kinetic energy and, 164–166 Dissociation The process in which individual positive and negative ions are released from an ionic compound that is dissolved in solution, 254 Arrhenius bases and, 254 Distinguishing electron The last electron added to the electron configuration for an element when electron subshells are filled in order of increasing energy, 72 identity of, and periodic table, 72–73 Disulfide nomenclature for, 432 preparation of, from thiols, 431 reduction of, 431 Disulfide bond cysteine and, 663 protein tertiary structure and, 675 DNA. See Deoxyribonucleic acid DNA helicase, 745 DNA ligase, 746 DNA polymerase, 745

DNA replication The biochemical process by which DNA molecules produce exact duplicates of themselves, 745 bidirectional nature of, 746 enzymes for, 745–746 Okazaki fragments and, 745–746 overview of, 745 summary-diagram for, 748 synthetic bases and, 738 DNA sequencing A method by which the base sequence in a DNA molecule (or a portion of it) is determined, 769 dideoxyribonucleotide triphosphates and, 769–771 human genome project and, 769 selective interruption of polynucleotide synthesis and, 769–771 steps in process of, 770–771 Dopamine, neurotransmitter function of, 528 Double covalent bond A covalent bond in which two atoms shared two pairs of electrons, 111 molecules containing, examples of, 112 notation for, 112 relative strength of, 111–112 Double-replacement reaction A chemical reaction in which two substances exchange parts with one another and form two different substances, 225 examples of, 225 general equation for, 225 Dynamite, explosive power of, 167 Earth’s crust, elemental composition of, 9–10 Eicosanoid An oxygenated C20 fatty acid derivative that functions as a messenger lipid, 644 biochemical effects of, 644 leukotrienes as, 645 prostaglandins as, 645 thromboxanes as, 645 types of, 644–645 Electrochemical gradient chemiosmotic coupling and, 801–802 Electrolyte A substance whose aqueous solution conducts electricity, 278 blood plasma concentrations of, 281 body fluids and, 283 concentration of, equivalence unit and, 280–281 intervenous replacement solutions and, 280 measurement of strength of, 280 strong, 279–280 weak, 279–280 Electron A subatomic particle that possesses a negative electrical charge, 51 bonding, 110 location of, within atom, 52 nonbonding, 110 orbitals for, 66–67 properties of, 51–52 sharing of, 84, 108–109 shells for, 63, 65, 67 spin of, 66–67 subshells for, 65–67 transfer of, 84, 87–89 valence, 84–86

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Index/Glossary

Electron cloud concept of, 52 Electron configuration A statement of how many electrons an atom has in each of its electron subshells, 68 interpretation of, 68 periodic law and, 71–72 periodic table location of elements and, 72–73 procedures for writing, 68–71 valence electrons and, 84–86 Electron orbital A region of space within an electron subshell where an electron with a specific energy is most likely to be found, 66 maximum electron occupancy of, 66 occupancy of, rules for, 67–69 overlap of, in bond formation, 109 size/shape of, 66 Electron shell A region of space about a nucleus that contains electrons that have approximately the same energy and that spend most of their time approximately the same distance from the nucleus, 63 energy order for, 63 maximum electron occupancy of, 65 notation for, 63 number of subshells within, 65 outermost, 84 Electron spin orbital diagrams and, 68–69 rules concerning, 67 Electron subshell A region of space within an electron shell that contains electron that have the same energy, 65 energy order for, 65, 68 maximum electron occupancy of, 65 notation for, 65 number of orbitals within, 66 types of, 65 Electron transport chain A series of biochemical reactions in which electrons and hydrogen ions from NADH and FADH2 are passed to intermediate carriers and then ultimately react with molecular oxygen to produce water, 794–795 cyanide poisoning and, 801 membrane–protein complexes associated with, 795 oxygen consumption and, 798–799 reactions of, 795–800 water production and, 798–799 Electronegativity A measure of the relative attraction that an atom has for the shared electrons in a bond, 122–123 use of, in determining bond type, 125–126 use of, in determining molecular polarity, 128–129 values, listing of, 123 values, periodic trends in, 123 Electrophoresis The process of separating charged molecules on the basis of their migration toward charged electrodes associated with an electric field, 662 apparatus diagram, 662 DNA sequencing and, 771 Electrostatic interaction An attraction or repulsion that occurs between charged particles, 164

form of potential energy, 164 protein tertiary structure and, 675–676 Element A pure substance that cannot be broken down into simpler pure substances by ordinary chemical means such as a chemical reaction, an electric current, heat, or a beam of light; a pure substance in which all atoms present have the same atomic number, 6, 54 abundances of, in different realms, 9–10 alkali metal, 60, 75 alkaline earth, 60, 75 characteristics of, 7–9 chemical symbols for, 11–12 classification systems for, 73–75 discovery of, 9–10 groups of, within periodic table, 59–61 halogen, 60, 75 homoatomic molecules and, 13–14 inner transition, 73–75 isotopic forms for, 54–56 listing of, 12, inside front cover metallic, 62–63, 73 naming of, 11 noble gas, 60, 73–75 nonmetallic, 62–63, 73 number of known, 9–10 periods of, within periodic table, 59–61 representative, 73–75 synthetic (laboratory-produced), 9 synthetic, listing of, 301 synthetic, uses for, 301 transition, 73–75 transuranium, 301 Elimination reaction A chemical reaction in which two groups or two atoms on neighboring carbon atoms are removed, or eliminated, from a molecule, leaving a multiple bond between the two carbon atoms, 412 alcohol dehydration, 412–415 Embden, Gustav, 814 Emulsification lipid bile acids, 640–641 Emulsifier A substance that can disperse and stabilize water-insoluble substances as colloidal particles in an aqueous solution, 640 bile acids as, 640–641 glycerophospholipids as, 632 lipid digestion, need for, 843 mono- and diacylglycerols as, 621 Enantiomers Stereoisomers whose molecules are nonsuperimposable mirror images of each other, 561 examples of, 561 Fischer projections formulas for, 561–565 interaction with plane-polarized light, 567–568 properties of, 566–568 recognizing, 562–565 Endothermic change of state A change of state in which heat energy is absorbed, 176 examples of, 177 Endothermic chemical reaction A chemical reaction in which a continuous input of energy is needed for the reaction to occur, 234

A-37

Energy activation, 233–234 atomic, 313 contrasted with matter, 1 free, 786 heat, units for, 43 kinetic, 164–166 nuclear, 313 potential, 164–166 Energy-storage lipid triacylglycerol, 614–618 Enflurane, 425 Enkephalins, 668 Enzymatic browning factors that control, 708 phenolase and, 708 Enzyme An organic compound that acts as a catalyst for a biochemical reaction, 698 action of, induced-fit model for, 704–705 action of, lock-and-key model for, 704 active site of, 704 allosteric, 713 aminotransferase, 880 carbohydrate digestion and, 811–813 citric acid cycle and, 789–794 classification of, by structure, 699 classification of, by type of reaction catalyzed, 700–703 conjugated, 699 cyclooxygenase, 646 DNA replication and, 745–746 enzyme-substrate complex for, 704–705 extremozymes, 706 general characteristics of, 698–699 gluconeogenesis and, 830–831 glycogenesis and, 831 glycogenolysis and, 829 glycolysis and, 814–818 helicobacter pylori bacteria and, 707 kinase, 814 lipid digestion and, 842–844 medical uses for, 718–719 models for action of, 704–705 mutase, 818 nomenclature of, 699–703 oxidative deamination and, 882–883 protein digestion and, 875–876 proteolytic, 715, 876 restriction, 766–767 ribozyme, 758 RNA synthesis and, 750 simple, 699 synthase, 790 terminology, associated with structure, 699 transamination and, 879–880 turnover number and, 708 Enzyme activity A measure of the rate at which an enzyme converts substrate to products in a biochemical reaction, 706 enzyme concentration and, 709 factors that affect, 706–710 inhibition of, 710–712 pH and, 706–707 regulation of, 713–715 saturation curve and, 707 substrate concentration and, 707–708

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A-38

Index/Glossary

Enzyme activity (Continued) summary-diagram for, 709 temperature and, 706 Enzyme inhibition antibiotics and, 715–718 summary-diagram for, 712 Enzyme inhibitor A substance that slows or stops the normal catalytic function of an enzyme by binding to it, 710 irreversible, 711 reversible competitive, 710–712 reversible noncompetitive, 711–712 types of, 710–712 Enzyme regulation allosteric enzymes and, 713–714 covalent modification and, 715 feedback control and, 713–714 zymogens and, 714–715 Enzyme specificity absolute, 705 group, 705 linkage, 705 specificity of, types of, 705 stereochemical, 705 types of, 704 Enzyme–substrate complex The intermediate reaction species that is formed when a substrate binds to the active site of an enzyme, 704 Ephedrin, 528 Epimers Diastereomers whose molecules differ only in the configuration at one chiral center, 563 examples of, 563 Epinephrine carbohydratae metabolism and, 837 central nervous system stimulant, 528–529 Equation coefficient A number that is placed to the left of a chemical formula of a substance in a chemical equation that changes the amount, but not the identity, of the substance, 147 determination of, 147–149 molar interpretation of, 150–151 use of, in chemical calculations, 151–155 Equilibrium A condition in which two opposite processes take place at the same rate, 179 characteristics of, 179 Equilibrium constant A numerical value that characterizes the relationship between the concentrations of reactants and products in a system at chemical equilibrium, 239 magnitude, calculation of, 241–242 rules for writing, 239–241 temperature dependence of, 242 value of, and reaction completeness, 242–243 Equilibrium position A qualitative indication of the relative amounts of reactants and products present when a chemical reaction reaches equilibrium, 242 terminology associated with, 242–243 Equivalent The molar amount of an ion needed to supply one mole of positive or negative charge, 280 electrolyte concentration and, 280–281 use of, in calculations, 281–282

Ergocalciferol, 726–727 Essential amino acid An amino acid needed in the human body that must be obtained from dietary sources because it cannot be synthesized within the body from other substances, in adequate amounts, 658 listing of, 658 Essential fatty acid A fatty acid needed in the human body that must be obtained from dietary sources because it cannot be synthesized within the body, in adequate amounts, from other substances, 620 importance of, 620–621 linoleic acid, 620–621 linolenic acid, 620–621 lipogenesis and, 864 Ester A carboxylic acid derivative in which the —OH portion of the carboxyl group has been replaced with an —OR group, 487 chemical reaction summary for, 498 cyclic, 489 flavor/fragrance agent function for, 491–492 formation of, acid anhydride and, 502 generalized formula for, 487 hydrogen bonding and, 495 hydrolysis of, 495–496 inorganic acid, 503–505 IUPAC-common name contrast for, 490 line-angle structural formulas for, 490 medicinal function for, 492–493 nitric acid, 503 nomenclature of, 489–491 pheromone function for, 492 phosphoric acid, 503–505 physical properties of, 495 physical-state summary for, 496 preparation of, from carboxylic acids, 487–488 saponification of, 496–497 sulfur analogs of, 497–498 sulfuric acid, 503 Esterification reaction The reaction of a carboxylic acid with an alcohol (or phenol) to produce an ester, 487 examples of, 487–488 Estradiol, 642 Estrogens biochemical functions of, 642 preparation of, from cholesterol, 869 ETC. See Electron transport chain Ethanol amount in beverages, 405–406 preparation of, 404 properties of, 404–405 pyruvate reduction and, 824 toxicity of, 404 uses for, 404–405 Ethanol fermentation The enzymatic anaerobic conversion of pyruvate to ethanol and carbon dioxide, 824 net reaction for, 824 Ethene industrial uses of, 367 plant hormone function for, 367 Ether An organic molecule in which an oxygen atom is bonded to two carbon atoms by single bonds, 422

chemical reactions of, 426–427 cyclic, 428 generalized formula for, 423 hydrogen bonding and, 427 IUPAC-common name contrast, 424 line-angle structural formulas for, 423 nomenclature of, 423–425 physical properties of, 427 physical-state summary for, 427 preparation of, from alcohols, 413–415 sulfur analogs of, 431–432 use of, as anesthetics, 425 use of, as gasoline additive (MTBE), 426 Ethylene glycol PET monomer, 499 properties of, 406 toxicity of, 406 uses for, 406 Ethylene oxide, 428 Eugenol, 422 Eukaryotic cell A cell in which the DNA is found in a membrane-enclosed nucleus, 779 characteristics of, 779–780 Evaporation The process in which molecules escape from the liquid phase to the gas phase, 177 factors affecting rate of, 177 in closed container, equilibrium and, 177–179 kinetic molecular theory and, 177 process of, 176–177 Exact number A number whose value has no uncertainty associated with it, 26 Exercise fuel consumption and, 853 high-intensity versus low-intensity, 853 Exon A gene segment that conveys (codes for) genetic information, 751 heterogeneous nuclear RNA and, 751–752 splicing and, 751–752 Exothermic change of state A change of state in which heat energy is given off, 177 examples of, 177 Exothermic chemical reaction A chemical reaction in which energy is released as the reaction occurs, 234 Expanded structural formula A structural formula that shows all atoms in a molecule and all bonds connecting the atoms, 324 examples of, 324 Extremozyme, 706 Facilitated transport The transport process in which a substance moves across a cell membrane, with the aid of membrane proteins, from a region of higher concentration to a region of lower concentration without the expenditure of cellular energy, 639 process of, characteristics for, 639–640 FAD. See flavin adenine dinucleotide FADH2. See flavin adenine dinucleotide Fat A triacylglycerol mixture that is a solid or semi-solid at room temperature, 617 animal, 617 artificial, 621, 625

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Index/Glossary

brown, 803 chemical reactions of 621–629 dietary considerations and, 618–621 general properties of, 617–618 partial hydrogenation of, 625–626 property-contrast with oils, 617–618 rancidity of, 627 trans, 626 Fat substitutes, 621, 624 Fatty acid A naturally occurring monocarboxylic acid, 609 biochemical oxidation of, 846–851 biosynthesis of, 858–864 essential, 620–621 lipogenesis and, 858–864 monounsaturated, 610–613 nomenclature for, 610–612 omega-3, 611–612 omega-6, 611–612 physical properties of, 613–614 polyunsaturated, 610–613 saturated, 610, 612 structural characteristics of, 609–613 trans, and blood cholesterol levels, 626 types of, 609–613 Fatty acid micelle A micelle in which fatty acids and/or monoacylglycerols and some bile are present, 843 lipid digestion and, 843–844 Fatty acid oxidation activation step in, 846–847 ATP production and, 851–854 b-oxidation pathway and, 847–851 human body preferences for, 854 transport and, 847 Feedback control A process in which activation or inhibition of the first reaction in a reaction sequence is controlled by a product of the reaction sequence, 713 Fermentation process A biochemical process by which NADH is oxidized to NAD⫹ without the need for oxygen, 823 ethanol, 824 lactate, 823–824 Ferritin, hemoglobin catabolism and, 892 FeSP. See iron sulfur protein Fiber dietary, 594 Fibrous protein A protein whose molecules have an elongated shape with one dimension much longer than others, 679 alpha-keratin, 680 collagen, 680–681 occurrence and function, 679 property contrast with globular proteins, 679 tooth enamel and, 100 Fischer, Emil, 562 Fischer projection formula A two-dimensional structural notation for showing the spatial arrangement of groups about chiral centers in molecules, 561 amino acids and, 658–659 conventions for drawing, 562–565 d and l designations for, 562–565 monosaccharides and, 562–565 Flavin adenine dinucleotide citric acid cycle and, 791–793

electron transport chain fuel, 794–795 FAD form of, 782–783 FADH2 form of, 782–783 general metabolic function of, 782 oxidized form of, 782–783 reduced form of, 782–783 structural subunits with, 782 Flavin adenine mononucleotide, b oxidation pathway and, 847–849 Flavin mononucleotide electron transport chain and, 795–796 structure of, 796 Flavone, generalized structure of, 805 Flavonoid, antioxidant properties of, 805 generalized structure of, 805 sources of, 805 Flavonol, generalized structure of, 805 FMN. See Flavin mononucleotide Folate coenzyme functions of, 724 dietary sources of, 725 structure of, 722–723 Food preservation, radiation use and, 307 Formaldehyde polymers involving, 463 properties of, 450 Formalin, 450 Formula chemical, 15 structural, types of, 324–326, 335–337 Formula mass The sum of the atomic masses of all the atoms represented in the chemical formula of a substance, 137 calculation of, 138 relationship to molar mass, 140–141 relationship to molecular mass, 137 Formula unit The smallest whole-number repeating ratio of ions present in an ionic compound that results in charge neutrality, 94 ionic compounds and, 94 Free energy, strained bonds and, 786–788 Free radical An atom, molecule, or ion that contains an unpaired electron, 304 formation of, ionizing radiation and, 304 hydroxyl, 304, 805–806 superoxide ion, 805–806 water, 304 Freezing, process of, 176–177 Freezing point, depression of, solutes and, 210 Freons, 351 Fructose carbohydrate digestion product, 812 consumption figures for, 588 glycolysis and, 820–821 natural food sources and, 588–589 occurrence of, 573 structure of, 573 Fructose 1-phosphate, glycolysis and, 821 Fructose 1,6-bisphosphate gluconeogenesis and, 831 glycolysis and, 816–817 Fructose 6-phosphate gluconeogenesis and, 831 glycolysis and, 814–816 Fumarate amino acid degradation product, 890

A-39

citric acid cycle and, 792, 794 urea cycle and, 885–887 Fumaric acid, 479, 482–483 Functional group The part of an organic molecule where most of its chemical reactions occur, 361 alcohol, 400 alkene, 362 alkyne, 382 amide, 532 amine, 515 amino, 515 armomatic hydrocarbon, 386 carbonyl, 442 carboxyl, 473–474 carboxylic acid, 473–474 ester, 487 ether, 423 hydroxyl, 400 nomenclature, priority ranking and, 446 phenol 419 sulfhydryl, 429 sulfoxide, 464 thiocarbonyl, 464 thioester, 497 thiol, 429 Functional group isomers Constitutional isomers that contain different functional groups, 426 alcohol-ether, 426–427 aldehyde-ketone, 450 carboxylic acid-ester, 494 thiol-thioether, 431 Furan, 428 Fused-ring aromatic hydrocarbon An aromatic hydrocarbon whose structure contains two or more rings fused together, 390 cancer and, 391 examples of, 390–391 Galactose carbohydrate digestion product, 812 glycolysis and, 820–821 occurrence of, 573 structure of, 572–573 Galactosemia, 585 Gamma ray A form of high-energy radiation without mass or charge that is emitted by certain radioactive nuclei, 294 characterization of, 296 emission of, equations for, 296 ion pair formation and, 305 notation for, 296 nuclear medicine and, 312 penetrating ability of, 305 use of, food irradiation and, 307 Gamma-ray emission The radioactive decay process in which a gamma ray is emitted from an unstable nucleus, 296 equations for, 296 Gangliosides, 635 Garlic odiferous compounds present, 432 sulfur-containing compounds and, 432 Gas The physical state characterized by an indefinite shape and an indefinite volume; the physical state characterized by a

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Index/Glossary

complete dominance of kinetic energy (disruptive forces) over potential energy (cohesive forces), 2, 165 condensation of, 176–177 deposition of, 176–177 distinguishing characteristics of, 2, 164 kinetic molecular theory of matter applied to, 166 solubility of, in water, 193–194 Gas law A generalization that describes in mathematical terms the relationships among the amount, pressure, temperature, and volume of a gas, 167 Boyle’s, 168–170 Charles’s, 170–171 combined, 172 Dalton’s, of partial pressures, 173–175 ideal, 172–173 summary diagram for, 175 variables in, 167–168 Geiger counter radiation detection and, 306–307 Gelatin from collagen, 687 Gene A segment of a DNA strand that contains the base sequence for the production of a specific hnRNA/mRNA molecule, 749 DNA and, 749–750 hnRNA and, 749–751 mRNA and, 749–751 number of, human genome and, 749–750 Genetic code The assignment of the 64 mRNA codons to specific amino acids (or stop signals), 752 codons and 753–756 degeneracy of, 753–754 synonyms and, 753 Genetic engineering, 765–768 Genome All of the genetic material (the total DNA) contained in the chromosomes of an organism, 749 human, gene content of, 749–750 human, nucleotide base pair content of, 749–750 human, project ENCODE and, 752 Global warming carbon dioxide and, 227 methane and, 325 Globular protein A protein whose molecules have peptide chains that are folded into spherical or globular shapes, 679 hemoglobin, 681 myoglobin, 681 occurrence and function, 679 property contrast with fibrous proteins, 679 Glucagon, carbohydrate metabolism and, 837 Glucocorticoids biochemical functions of, 643 synthesis of, from cholesterol, 869 Glucogenic amino acid An amino acid that has a carbon-containing degradation product that can be used to produce glucose via gluconeogenesis, 890 listing of, 890 Gluconeogenesis The metabolic pathway by which glucose is synthesized from noncarbohydrate materials, 830

ATP consumption and, 831–832 contrasted with glycolysis, 830–831 steps in, 830–831 Glucose blood testing for, 456 carbohydrate digestion product, 812 concentration in blood, 572 Cori cycle and, 832 diabetes and, 836 gluconeogenesis and, 830–831 glycemic index and, 597 glycogenolysis and, 829 glycolysis and, 813–820 natural food sources and, 588–589 net equation for conversion to acetyl CoA, 827 occurrence of, 571–572 oxidation to pyruvate, 813–820 structure of, 571 synthesis of, noncarbohydrate materials and, 830–832 urine testing for, 456 Glucose metabolism summary-diagram for, 835 terminology associated with, 832–833 Glucose oxidation, human body preferences for, 854 Glucose 1-phosphate glycogenesis and, 828–829 glycogenolysis and, 829 glycolysis and, 821 Glucose 6-phosphate gluconeogenesis and, 831 glycogenesis and, 828–829 glycogenolysis and, 829 glycolysis and, 814 pentose phosphate pathway and, 834 Glutamate derivatives of, transamination and, 879 oxidative deamination reactions and, 882–883 transamination reactions and, 879–880 Glutaric acid, derivatives, metabolic functions for, 482–483 Glutathione, 668 Glycan An alternate name for a polysaccharide, 587 Glycemic effect, 597 Glycemic index, 597 Glyceraldehyde glycolysis and, 821 structure of, 570–571 Glyceraldehyde 3-phosphate, glycolysis and, 816–817 Glyceric acid, 482–483 Glycerin, 407 Glycerol derivatives of, glycolysis and, 816 properties of, 407 triacylglycerol metabolism product, 846 uses for, 407 Glycerol metabolism dihyroxyacetone phosphate and, 846 glycerol 3-phosphate and, 846 steps in, 846 Glycerol 3-phosphate glycerol metabolism and, 846 shuttle system particpant, 826–827

Glycerolipid, summary diagram, types of, 634 Glycerophospholipid A lipid that contains two fatty acids and a phosphate group esterified to a glycerol molecule and an alcohol esterified to the phosphate group, 629 generalized structure of, 629 head–two tail structure of, 631–632 phosphatidylcholines, 630, 632 phosphatidylethanolamines, 630, 632 phosphatidylserines, 630, 632 polarity of, 631–632 structural-contrast with triacylglycerol, 629 Glycocholic acid, 641 Glycogen degradation of, 829 glycogenesis and, 828–829 glycogenolysis and, 829 hydrolysis of, 592 properties of, 592 structure of, 592 synthesis of, 828–829 Glycogenesis The metabolic pathway by which glycogen is synthesized from glucose 6-phosphate, 828 ATP consumption and, 829 steps in, 828–829 Glycogenolysis The metabolic pathway by which glucose 6-phosphate is produced from glycogen, 829 steps in, 829 Glycol A diol in which the two —OH groups are on adjacent carbon atoms, 406 examples of, 406 Glycolic acid, 479 Glycolipid A lipid molecule that has one or more carbohydrate or carbohydrate derivative units covalently bonded to it, 596 cell recognition and, 596–597 Glycolysis The metabolic pathway by which glucose (a C6 molecule) is converted into two molecules of pyruvate (a C3 molecule), chemical energy in the form of ATP is produced, and NADH reduced coenzymes are produced, 813 anaerobic nature of, 813 ATP production and, 818–819 contrasted with gluconeogenesis, 830–831 net equation for, 818 overview-diagram for, 815 reactions of, 813–821 regulation of, 821–822 six-carbon stage of, 814–816 three-carbon state of, 816–819 Glycoprotein A protein molecule that has one or more carbohydrate or carbohydrate derivative units covalently bonded to it, 596 cell recognition and, 596–597 collagen, 687 immunoglobulins, 687–689 Glycoside An acetal formed from a cyclic monosaccharide by replacement of the hemiacetal carbon atom —OH group with an —OR group, 579 nomenclature of, 579, 581

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Index/Glossary

Glycosidic linkage The bond in a disaccharide resulting from the reaction between the hemiacetal carbon atom —OH group of one monosaccharide and a —OH group on the other monosaccharide, 582 disaccharides and, 582–587 summary diagram for, 595 Gold, lack of corrosion of, 232 Grain alcohol, 404 Gram The base unit of mass in the metric system, 24 compared to English system units, 24 Greenhouse gases, global warming and, 227 Group A vertical column of elements in the periodic table, 60 in periodic table, notation for, 60 Guanine nucleotide subunit, 735–737 structure of, 735–737 Hair denaturation of, 686 permanent for, 686 pigmentation of, melanin and, 452 Half life (t1/2) The time required for one-half of a given quantity of a radioactive substance to undergo decay, 297 magnitude, interpretation of, 297–300 selected values for, table of, 298 use of, in calculations, 298–300 Halogen A general name for any element in Group VIIA of the periodic table, 60 London forces and, 186 periodic table location of, 60, 75 Halogenated alkane An alkane derivative in which one or more halogen atoms are present, 350 IUPAC-common name contrast for, 350 nomenclature for, 350–351 physical properties of, 352 Halogenated cycloalkane A cycloalkane derivative in which one or more halogen atoms are present, 350 preparation of, from alcohols, 417–418 Halogenation reaction A chemical reaction between a substance and a halogen in which one or more halogen atoms are incorporated into molecules of the substance; an addition reaction in which a halogen is incorporated into molecules of an organic compound, 347, 375 alcohol, 417–418 alkane, 347–350 alkene, 375 aromatic hydrocarbon, 390 cycloalkane, 350 Halothane, 425 Handedness molecular, notation for, 561–565 molecular, recognition of, 558–560 Haworth, Walter Norman, 576 Haworth projection formula A twodimensional structural notation that specifies the three-dimensional structure of a cyclic form of a monosaccharide, 576 conventions for drawing, 576 monosaccharides and, 576–577

HDL biochemical functions of, 690–691 structural characteristics of, 690–691 Heart attack, enzyme analysis and, 719 Heat energy, units for, 43 Helicobacter pylori conditions for existence of, 707 enzymes present in, 707 stomach ulcers and, 707 Heme, structure of, 892 Hemiacetal An organic compound in which a carbon atom is bonded to both a hydroxyl group (—OH) and an alkoxy group (—OR), 458 cyclic, formation of from monosaccharides, 574–577 cyclic, structure of, 458–459 nomenclature for, 462 preparation of, from aldehydes, 458–459 preparation of, from ketones, 458–459 reaction of, with alcohols, 460 Hemoglobin biochemical function of, 681 catabolism of, 892–895 tertiary structure of, 678 Hemoglobin catabolism bile pigments and, 893–896 carbon monoxide production and, 893 heme degradation products and, 892–896 oxygen consumption and, 893 Hemolysis, hypertonic solutions and, 213–214 Henderson–Hasselbalch equation, buffer systems and, 277–278 Henry, William, 194 Henry’s law The amount of gas that will dissolve in a liquid at a given temperature is directly proportional to the partial pressure of the gas above the liquid, 194 Heparin properties of, 596 structure of, 596 Heroin, 530 Heteroatomic molecule A molecule in which two or more kinds of atoms are present, 13 examples of, 13–14 Heterocyclic amine An organic compound in which nitrogen atoms of amino groups are part of either an aromatic or a nonaromatic ring system, 525 ring systems in, 525 Heterocyclic organic compound A cyclic organic compound in which one or more of the carbon atoms in the ring have been replaced with atoms of other elements, 428 amides as, 533 amines as, 516, 525 esters as, 489 ethers as, 428 lactams as, 533 lactones as, 489 Heterogeneous mixture A mixture that contains visibly different phases (parts), each of which has different properties, 6 characteristics of, 6–9 Heterogeneous nuclear RNA (hnRNA) RNA formed directly by DNA transcription, 748

A-41

exons and introns and, 751–752 post-transcription processing of, 751–752 Heteropolysaccharide A polysaccharide in which more than one type of monosaccharide monomer (usually two) are present, 588 examples of, 589, 595–596 HFCS. See High fructose corn syrup High fructose corn syrup production of, 588 types of, 588 uses for, 588 High-energy compound A compound that has a greater free energy of hydrolysis than that of a typical compound, 786 phosphate containing, 786–788 strained bonds and, 786–788 Histamine, allergy response from, 529 Histone, 746 HMG-CoA. See 3-Hydroxy-3-methylglutaryl CoA hnRNA. See Heterogeneous nuclear RNA Holoenzyme The biochemically active conjugated enzyme produced from an apoenzyme and a cofactor, 699 Homoatomic molecule A molecule in which all atoms present are of the same kind, 13 examples of, 13–14 Homogeneous mixture A mixture that contains only one visibly distinct phase (part), which has uniform properties throughout, 6 characteristics of, 6–9 Homopolysaccharide A polysaccharide in which only one type of monosaccharide monomer is present, 587–588 examples of, 588, 591–594 Hormone A biochemical substance, produced by a ductless gland, that has a messenger function, 641 adrenocortical, 643 carbohydrate metabolism control and, 835–837 peptide, 667–668 sex, 642–643 Human body density measurement for, 40 elemental composition of, 11 normal temperature for, 44 percent body fat, determination of, 40 Human genome, compared to human transcriptome, 752 Human genome project, results from, 749–750 Human transcriptome, compared to human genome, 752 Hyaluronic acid properties of, 596 structure of, 595–596 Hydration reaction An addition reaction in which H2O is incorporated into molecules of an organic compound, 376 alkenes, 376 b oxidation pathway and, 848 Hydrocarbon A compound that contains only carbon atoms and hydrogen atoms, 322 alkane, 323–340 alkene, 361–382 alkyne, 382–384

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Index/Glossary

Hydrocarbon (Continued) aromatic, 384–391 cycloalkane, 340–344 derivatives of, 322–323 saturated, 323 unsaturated, 323 Hydrocarbon derivative A compound that contains carbon and hydrogen and one or more additional elements, 322–323 Hydrocodone, 530, 532 Hydrogen acidic, 257–258 deuterium, 55 isotopes of, 55 nonacidic, 257–258 protium, 55 tritium, 55 Hydrogen bond An extra strong dipole-dipole interaction between a hydrogen atom covalently bonded to a small, very electronegative element (F, O, or N) and a lone pair of electrons on another small, very electronegative element (F, O, or N), 182 characteristics of, 182–184 effects of, properties of water and, 183–184 predicting occurence of, 182–183 strength of, factors affecting, 181–182 Hydrogen bonding alcohols, 409–410 aldehydes, 453 amides, 536–537 amines, 519 carboxylic acids, 483 DNA base-pairing and, 742–744 esters, 495 ethers, 427 ketones, 453 protein secondary structure and, 671–672 protein tertiary structure and, 675–676 Hydrogen peroxide, 805–806 Hydrogenation reaction An addition reaction in which H2 is incorporated into molecules of an organic compound, 374 aldehyde, 457 alkene, 374–375 ketone, 457 lipogenesis and, 861–862 trans fats and, 625–626 triacylglycerols, 625–626 Hydrohalogenation reaction An addition reaction in which a hydrogen halide (HCl, HBr, or HI) is incorporated into molecules of an organic compound, 375 alkene, 375–376 Hydrolase An enzyme that catalyzes a hydrolysis reaction in which the addition of a water molecule to a bond causes the bond to break, 701 examples of, 701–702 Hydrolysis salt, blood plasma pH and, 274 salt, chemical equations for, 273–274 salt, guidelines for predicting, 270 salt, solution pH and, 273–274 Hydrolysis reaction The reaction of a salt with water to produce hydronium ion or hydroxide ion or both; the reaction of a

compound with H2O, in which the compound splits into two or more fragments as the elements of water (H— and —OH) are added to the compound, 270, 460 acetals, 460–462 acid anhydrides, 502 acid chlorides, 501 adenosine phosphates, 781–782 amides, 540–541 disaccharides, 583–587 esters, 495–497 proteins, 683–684 triacylglycerols, 621–623 Hydroperoxides, from ethers, 426 Hydrophobic attractions, protein tertiary structure and, 676 Hydroquinone, 420 a-Hydroxy carboxylic acid, skin care and, 481 3-Hydroxy-3-methylglutaryl CoA, ketogenesis and, 856–857 b-Hydroxyacyl CoA, b oxidation pathway and, 847–848 hydroxyapatite, 100 b-Hydroxybutyryl ACP, lipogenesis and, 862 b-Hydroxybutyrate, as ketone body, 854–855 Hydroxyl free radical, 304, 805–806 Hydroxyl group The —OH functional group, 400 Hypertonic solution A solution with a higher osmotic pressure than that found within cells, 214 hemolysis and, 213–214 Hypotonic solution A solution with a lower osmotic pressure than that found within cells, 213 crenation and, 213–214 Ibuprofen cyclooxygenase inhibitor, 646 pharmacology of, 480 structure of, 480 Ideal gas constant, value of, 173 Ideal gas law A gas law that describes the relationship among the four variables temperature, pressure, volume, and molar amount for a gaseous substance at a given set of conditions, 172 mathematical form of, 172 use of, in calculations, 173 Immunoglobulin A glycoprotein produced by an organism as a protective response to the invasion of microorganisms or foreign molecules, 687 generalized structural characteristics, 687–688 mode of action, 687–689 Induced-fit model, enzyme action and, 704–705 Inexact number A number whose value has a degree of uncertainty associated with it, 26 Inner transition element An element located in the f area of the periodic table, 75 electronic characteristics of, 75 periodic table location of, 75 Inorganic chemistry The study of all substances other than hydrocarbons and their derivatives, 322 contrasted with organic chemistry, 322

Insulin carbohydrate metabolism and, 836 human need for, delivery modes for, 836 primary structure of, 671, 675 substitutes for human, 671 Integral membrane protein A membrane protein that penetrates the cell membrane, 638 Intermolecular force An attractive force that acts between a molecule and another molecule, 181 contrasted with intramolecular forces, 181 dipole-dipole interactions, 181, 185 effects of, on physical properties, 181–186 hydrogen bonds, 181–185 London forces, 184–186 summary diagram of, 185 types of, 181–186 Interstitial fluid electrolyte composition of, 283 Intracellular fluid electrolyte composition of, 283 Intron A gene segment that does not convey (code for) genetic information, 751 heterogeneous nuclear RNA and, 751–752 splicing and, 751–752 Iodine test, starch and, 591 Ion An atom (or group of atoms) that is electrically charged as a result of loss or gain of electrons, 87 categories of, 98 isoelectronic species and, 90 magnitude of charge on, 89–90 monoatomic, 98 notation for, 87 number of protons and electrons in, 88, 90 polyatomic, 98 Ion pair The electron and positive ion that are produced during an interaction between an atom or a molecule and ionizing radiation, 303 formation of, ionizing radiation and, 303–304 Ion product constant for water The numerical value 1.0 ⫻ 10⫺14, obtained by multiplying together the molar concentrations of H3O⫹ ion and OH⫺ ion present in pure water at 24 °C, 263–264 calculations involving, 264 numerical value of, 263–264 Ionic bond A chemical bond formed through the transfer of one or more electrons from one atom or group of atoms to another atom or group of atoms, 84 contrasted with covalent bond, 108–109 electronegativity differences and, 125–126 formation of, 91–92 Lewis structures and, 91–92 Ionic compound A compound in which ionic bonds are present, 84 binary, naming of, 94–98 contrasted with molecular compound, 108–109 formation of, electron transfer and, 91–92 formula units and, 94 formulas, determination of, 92–93, 100–101 general properties of, 83

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Index/Glossary

Lewis structures for, 91–92 nomenclature rule summary for, 102 polyatomic-ion containing, naming of, 101–102 structure units for, 93–94 Ionization The process in which individual positive and negative ions are produced from a molecular compound that is dissolved in solution, 254 Arrhenius acids and, 254 radiation and, 303 Ionizing radiation Radiation with sufficient energy to remove an electron from an atom or a molecule, 303 effects of, 303–304 free radical formation and, 304 ion-pair formation and, 303–304 penetrating ability of, 305 Iron corrosion of, 232 forms of, human body and, 74 functions for, human body and,74 use of, in steel, 3 Iron–sulfur protein electron transport chain and, 795–797 Irreversible enzyme inhibitor A molecule that inactivates enzymes by forming a strong covalent bond to an amino acid side-chain group at the enzyme’s active site, 711 mode of action, 711 Isocitrate, citric acid cycle, 791–792, 794 Isoelectric point The pH at which an amino acid solution has no net charge because an equal number of positive and negative charges are present, 661 amino acid, table of values for, 661 Isoelectronic species An atom and an ion, or two ions, that have the same number and configuration of electrons, 90 examples of, 90 Isoenzyme Forms of the same enzyme with slightly different amino acid sequences, 719 heart attack diagnosis and, 719 Isoeugenol, 422 Isoflurane, 425 Isomerase An enzyme that catalyzes the isomerization (rearrangement of atoms) of a substrate in a reaction, converting it into a molecule isomeric with itself, 701 examples of, 701–702 Isomers Compounds that have the same numbers and kinds of atoms but differ in the way the atoms are arranged, 326 alcohol, 403 aldehyde, 449–450 alkane, 326–329 alkene, 366–370 alkyne, 383 amine, 518–519 carboxylic acid, 493–494 cis–trans, for alkenes, 368–370 cis–trans, for cycloalkanes, 343–344 constitutional, 327 cycloalkane, 342–344 diastereoisomers, 561–565

enantiomers, 561–565 epimers, 563 ester, 493–494 ether, 426–427 ketone, 449–450 peptide, 667 positional, 366 skeletal, 367 stereoisomers, 561–565 structural, 327 types of, summary diagram, 566 Isopentenyl pyrophosphate cholesterol biosynthesis and, 866 Isoprene cholesterol biosynthesis and, 866 natural rubber and, 381 terpene structural unit, 371–372 Isopropyl alcohol preparation of, 405 properties of, 405 toxicity of, 405 uses for, 405 Isotonic solution A solution with an osmotic pressure that is equal to that within cells, 214 examples of, 214 Isotopes Atoms of an element that have the same number of protons and same number of electrons but different numbers of neutrons, 54 chemical properties of, 55 hydrogen, properties of, 55 known number of, 56 notation for, 55 percentage abundances of, for selected elements, 57 physical properties of, 55 relative masses of, for selected elements, 57 Jaundice, bilirubin concentrations and, 895–896 Joule metric unit, for heat energy, 43 relationship to calorie, 43 Ka, carboxylic acids, values for, 484 Kelvar, 542–543 a-Keratin biochemical function of, 680 structural characteristics of, 680 Keto acid, transamination reactions and, 879–880 b-Ketoacyl CoA, b oxidation pathway and, 847–848 Ketogenesis The metabolic pathway by which ketone bodies are synthesized from acetyl CoA, 856 Ketogenic amino acid An amino acid that has a carbon-containing degradation product that can be used to produce ketone bodies, 890 listing of, 890 a-Ketoglutarate amino acid biosynthesis from, 891 amino acid degradation product, 890 citric acid cycle and, 791, 794 a-Ketoglutaric acid, 482–483

A-43

Ketone A carbonyl-containing organic compound in which the carbonyl carbon atom has two other carbon atoms directly attached to it, 444 chemical reaction summary for, 462 commonly encountered, 450–451 cyclic, 445 functional group for, 444 generalized formula for, 444 hemiacetal formation and, 458–459 IUPAC-common name contrast for, 448 lachrymatory, 449 line-angle structural formulas for, 448 nomenclature of, 447–448 oxidation of, 455–457 physical properties of, 451–453 physical-state summary for, 451 preparation of, from alcohols, 415–417, 453–455 reaction with alcohols, 458–459 reduction of, 457 thio, 464 Ketone body One of the three substances (acetoacetate, beta-hydroxybutyrate, and acetone) produced from acetyl CoA when an excess of acetyl CoA from fatty acid degradation accumulates because of triacylglycerol carbohydrate metabolic imbalances, 854 acetoacetate, 854–855 acetone, 854–855 acidosis and, 858 biochemical importance of, 854 conditions for formation of, 854 b-hydroxybutyrate, 854–855 Ketose A monosaccharide that contains a ketone functional group, 569 common, listing of, 572 Ketosis, ketone body formation and, 857–858 Khorana, Har Gobind, 753 Kinase, function of, 814 Kinetic energy Energy that matter possesses because of particle motion, 164 disruptive forces and, 164–166 kinetic molecular theory of matter and, 164–166 temperature dependence of, 165 Kinetic molecular theory of matter A set of five statements used to explain the physical behavior of the three states of matter (solids, liquids, and gases), 163 applied to gaseous state, 166 applied to liquid state, 165–166 applied to solid state, 165 Boyle’s law and, 169 Charles’s law and, 171 concepts associated with, 164 evaporation and, 177 kinetic energy and, 164–166 osmosis and, 211 potential energy and, 164–166 Krebs, Hans Adolf, 788 Krebs cycle. See Citric acid cycle Lachrymator, aldehydes and ketones as, 449 Lactam A cyclic amide, 533 classifications for, 533

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Index/Glossary

Lactam (Continued) examples of, 533 nomenclature of, 533 structural charactistics of, 533 Lactate accumulation of, muscles and, 825 Cori cycle and, 832 pyruvate reduction and, 823–824 Lactate dehydrogenase (LDH), 719 Lactate fermentation The enzymatic anaerobic reduction of pyruvate to lactate, 823 net reaction for, 823 Lactation, immunoglobins and, 689 Lactic acid, 479–480, 482–483 Lactomer, condensation polymer, properties of, 500 Lactone A cyclic ester, 489 classification of, 489 examples of, 489 formation reaction for, 489 macrolide antibiotics, 493 nomenclature of, 491 occurrence in plants, 492 structural characteristics of, 489 Lactose hydrolysis of, 586 occurrence of, 586 structure of, 585 Lactose intolerance, 585 Lanosterol, cholesterol biosynthesis and, 866–867 Law of conservation of mass, 147 LDL biochemcial functions of, 690–691 structural characteristics of, 690–691 Le Châtelier, Henri Louis, 243 Le Châtelier’s principle If a stress (change of conditions) is applied to a system at equilibrium, the system will readjust (change equilibrium position) in the direction that best reduces the stress imposed on the system, 243 catalyst addition and, 246 concentration changes and, 243–244 pressure changes and, 245 temperature changes and, 244–245 Lecithins, 632 Length conversion factors involving, 35–36 metric units of, 23–24 Leukotriene A messenger lipid that is a C20fatty-acid derivative that contains three conjugated double bonds, 645 biochemical functions of, 645 structural characteristics of, 645 Levorotatory compound A chiral compound that rotates the plane of polarized light in a counterclockwise direction, 567 notation for, 567–568 Levulose, 573 Lewis, Gilbert N., 84, 86 Lewis structure A combination of Lewis symbols that represents either the transfer or the sharing of electrons in chemical bonds, 91 ionic compounds and, 91–92 molecular compounds and, 109–111

polyatomic ions and, 117–118 systematic procedures for drawing, 114–116 Lewis symbol The chemical symbol of an element surrounded by dots equal in number to the number of valence electrons present in atoms of the element, 84 determination of, 84–86 notation used in, 85–86 valence electrons and, 84–86 Lidocaine, 536 Ligase An enzyme that catalyzes the bonding together of two molecules into one, with the participation of ATP, 702 examples of, 702 Light, plane-polarized, 567 Line-angle structural formula A structural representation in which a line represents a carbon-carbon bond and a carbon atom is understood to be present at every point where two lines meet and at the ends of lines, 336 alcohols, 401 aldehydes, 446 alkanes, 335–337 alkenes, 365–366 alkynes, 383 amides, 533 amines, 516 carboxylic acids, 475 cycloalkenes, 362 esters, 490 ethers, 423 ketones, 448 Linoleic acid, 620–621 Linolenic acid, 620–621 Lipid An organic compound found in living organisms that is insoluble (or only sparingly soluble) in water but soluble in nonpolar organic solvents, 608 classification of, based on function, 609 emulsification, 609 energy-storage, 609 fatty-acid-containing, summary diagram for, 634 functions of, in humans, 609 membrane, 609 messenger, 609 protective-coating, 609 solubility characteristics of, 608 summary diagram for, based on function, 648 Lipid bilayer A two-layer-thick structure of phospholipids and glycolipids in which the nonpolar tails of the lipids are in the middle of the structure and the polar heads are on the outside surfaces of the structure, 637 cell membrane structure and, 637–638 Lipid digestion breakdown products from, 842–843 enzymes need for, 842–844 location for, within human body, 842–844 steps in, 844 Lipid metabolism ATP production and, 851–852 beta oxidation pathway and, 847–851 cholesterol, 864–867

ketogenesis, 856–857 lipogenesis, 858–864 relationship between carbohydrate metabolism and, 868–869, 895–897 relationship between protein metabolism and, 895–897 Lipitor, 867 Lipogenesis The metabolic pathway by which fatty acids are synthesized from acetyl CoA, 858 ACP complex formation and, 859–861 chain elongation and, 861–863 contrasted with beta oxidation pathway, 858–859 intermediates, relationship to citric acid cylce intermediates, 864 malonyl CoA formation and, 860 steps in, 861–862 unsaturated fatty acids and, 863–864 Lipoprotein A conjugated protein that contains lipids in addition to amino acids, 689 cholesterol and, 636 HDL as, 690–691 LDL as, 690–691 plasma, 690–691 Liquid The physical state characterized by an indefinite shape and a definite volume; the physical state characterized by potential energy (cohesive forces) and kinetic energy (disruptive forces) of about the same magnitude, 2, 165 boiling of, 180 distinguishing characteristics of, 2, 164 evaporation of, 176–177 freezing of, 176–177 intermolecular forces in, 181–186 kinetic molecular theory of matter applied to, 165–166 vapor pressures of, 179 Liter The base unit of volume in the metric system, 25 compared to English system units, 24–25 Lock-and-key model, enzyme action and, 704 Logarithm pH calculation, using, 266–268 pKa calculation, using, 269–270 significant figure rules for, 266 London, Fritz, 184 London force A weak temporary intermolecular force that occurs between an atom or molecule (polar or nonpolar) and another atom or molecule (polar or nonpolar), 184 characteristics of, 184–186 Lortab, 530 Lovastatin, cholesterol levels and, 867 Lowry, Thomas Martin, 254 Lyase An enzyme that catalyzes the addition of a group to a double bond or the removal of a group from a double bond in a manner that does not involve hydrolysis or oxidation, 701 examples of, 701–702 Lycopene, color and, 374 Lysosome An organelle that contains hydrolytic enzymes needed for cellular rebuilding, repair, and degradation, 779 biochemical functions for, 779

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Index/Glossary

Major mineral, importance of, human body and, 64 Malate, citric acid cycle and, 792, 794 Maleic acid, 479 Malic acid, 479–480, 482–483 Malonyl ACP formation of, 860 lipogenesis and, 860 Malonyl CoA, formation of, 860 Maltose hydrolysis of, 583–584 occurrence of, 582 structure of, 582–583 Marijuana pharmacology of, 429 structure of, 429 Markovnikov, Vladmir Vasilevich, 376 Markovnikov’s rule When an unsymmetrical molecule of the form HQ adds to an unsymmetrical alkene, the hydrogen atom from the HQ becomes attached to the unsaturated carbon atom that already has the most hydrogen atoms, 376 use of, addition reactions, 376–378 Mass A measure of the total quantity of matter in an object, 24 calculation of, using density, 41 conversion factors involving, 34–36 distinction between weight and, 24–25 metric units of, 24–25 Mass number The sum of the number of protons and the number of neutrons in the nucleus of an atom, 53 informational value of, 53 neutrons and, 53 non-uniqueness of, 55 use of, with chemical symbols, 54 Mass–volume percent The mass of solute in a solution (in grams) divided by the total volume of solution (in milliliters), multiplied by 100, 200 calculations involving, 202–203 mathematical equation for, 200 Matter Anything that has mass and occupies space, 1 changes in, 4–6 chemistry as study of, 1 classification procedure for, 9 classifications of, 6–9 contrasted with nonmatter, 1 physical states of, 2 plasma state for, 314 properties of, 2–4 states of, compressibility and, 163–164 states of, kinetic molecular theory and, 165–166 states of, property differences among, 163–164 states of, thermal expansion and. 163–164 Measurement The determination of the dimensions, capacity, quantity, or extent of something, 22 English system for, 22–23 metric system for, 22–25 rules for recording, 26 significant figure guidelines for, 26–27 uncertainty associated with, 26

Melanin hair-pigmentation and, 452 sunburn and, 452 Melatonin, 535–536 Melting, process of, 176–177 Membrane cell, 637 plasma, 637 Membrane lipid cholesterol, 635–636 classification type, 609 glycerophospholipid, 629–632 sphingoglycolipid, 634–635 sphingophospholipid, 632–633 summary diagram, types of, 634 Membrane protein A protein that is found associated with a membrane system of a cell, 679 types of, 638 Menaquinones, 728 Mendeleev, Dmitri Ivanovich, 59 Menthol properties of, 408 terpene structure of, 372 uses for, 408 Mercaptan, 430 Messenger lipid, 609 eicosanoids, 644–646 leukotrienes, 645 prostaglandins, 645 steroid hormones, 641–643 thromboxanes, 645 Messenger protein, 683 Messenger RNA (mRNA) RNA that carries instructions for protein synthesis (genetic information) to sites for protein synthesis, 748 codons and, 754–756 efficiency of utilization in protein synthesis, 762 formation of, splicing and, 751–752 translocation and, 759–761 Meta-, prefix, meaning of, 387 Metabolic intermediate compounds adenosine phosphates, 781–782 classifation of, by function, 785 coenzyme A, 784–785 flavin adenine dinucleotide, 782–783 nicotinamide adenine dinucleotide, 783–784 Metabolic pathway A series of consecutive biochemical reactions used to convert a starting material into an end product, 778 cyclic, 778 linear, 778 Metabolism The sum total of all the biochemical reactions that take place in a living organism., 777 anabolism portion of, 777–778 carbohydrate, 811–837 catabolism portion of, 777–778 glycerol, 846 lipids, 842–869 protein, 875–897 triacylglycerol, 846–851 Metal An element that has the characteristic properties of luster, thermal conductivity, electrical conductivity, and malleability, 62

A-45

fixed-charge, naming compounds and, 96–98 general properties of, 62, 75 human body composition and, 64 periodic table locations for, 63 types of, naming compounds and, 96–98 variable-charge, naming compounds and, 96–98 Meter The base unit of length in the metric system, 23 compared to English system units, 23–24 Methandrostenolone, 642 Methane global warming and, 325 natural gas and, 345 terrestrial sources of, 325 Methanol preparation of, 404 properties of, 404 toxicity of, 404 uses for, 404 Metric system compared with English system, 24 prefixes, table of, 24 prefixes, use of, 23–24 units of length, 23–24 units of mass, 24–25 units of volume, 25 Mevacor, 867 Mevalonate, cholesterol biosynthesis and, 866 Mevastatin, cholesterol levels and, 867 Meyer, Julius Lothar, 59 Meyerhof, Otto, 814 Micelle A spherical cluster of molecules in which the polar portions of the molecules are on the surface and the nonpolar portions are located in the interior, 624 fatty acid, lipid digestion and, 843–844 formation of, soaps and detergents, 624–625 Miescher, Friedrich, 734 Mineral classifications of, 64 major, human body and, 64 trace, human body and, 64 Mineral oil, 348 Mineral wax A mixture of long-chain alkanes obtained from the processing of petroleum, 648 contrasted with biological wax, 648 Mineralization, tooth enamel and, 100 Mineralocorticoids biochemical functions of, 643 synthesis of, from cholesterol, 869 Mirror image The reflection of an object in a mirror, 558 nonsuperimposability of, 558–559 superimposability of, 558–559 Mitochondria An organelle that is responsible for the generation of most of the energy for a cell, 779 biochemical functions for, 779–780 innermembrane of, 779–780 outermembrane of, 779–780 substructure within, 779–780 Mixed triacylglycerol A triester formed from the esterification of glycerol with more than one kind of fatty acid molecule, 616 structural formula for, 616

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A-46

Index/Glossary

Mixture A physical combination of two or more pure substances in which each substance retains its own chemical identity, 6 characteristics of, 6–9 comparison with compounds, 8 heterogeneous, 6–9 homogeneous, 6–9 separation of, by physical means, 6 types of, 6–9 Molar mass The mass, in grams, of a substance that is numerically equal to the substance’s formula mass, 140 conversion factors based on, 141 relationship to formula mass, 140–141 use of, in calculations, 143–146 Molarity The moles of solute in a solution divided by the liters of solution, 203 calculations involving, 203–205 mathematical equation for, 203 Mole 6.02 3 10 23 objects; the amount of a substance that contains as many elementary particles (atoms, molecules, or formula units) as there are atoms in exactly 12 grams of 12C, 139, 142 Avogadro’s number and, 139 chemical equations and, 150–151 chemical formulas and, 142–143 counting unit, use of a, 139 general calculations involving, 143–146 important relationships involving, summary of, 151–152 mass of, 140–142 number of objects in, calculation of, 139–140 Molecular collisions elastic, 164 inelastic, 164 Molecular compound A compound in which covalent bonds are present, 84 binary, naming of, 130–131 bonding model for, 109 contrasted with ionic compound, 108–109 general properties of, 83 Lewis structures for, 109–111 polarity of, 127–129 Molecular geometry A description of the three-dimensional arrangement of atoms within a molecule, 118 effects of nonbonding VSEPR electron groups on, 119–121 electron pair replusions and, 118–119 prediction of, using VSEPR theory, 118–121 role of central atom in determining, 118–121 sense of smell and, 112 sense of taste and, 122 Molecular mass calculation of, 138 relationship to formula mass, 137 Molecular polarity A measure of the degree of inequality in the attraction of bonding electrons to various locations within a molecule, 126 diatomic molecules and, 128 factors which determine, 127–128 tetraatomic molecules and, 128–129 triatomic molecules and, 128–129

Molecule A group of two or more atoms that functions as a unit because the atoms are tightly bound together, 13 achiral, 558 characteristics of, 13–14 chiral, interactions between, 568 chirality of, 557–560 classification of, by number of atoms, 13–14 classification of, by types of atoms, 13–14 conformations of, 327–329 diatomic, 13–14 geometry of, 118–121 handedness in, notation for, 561–565 handedness in, recognition of, 557–560 heteroatomic, 13–14 homoatomic, 13–14 ionic solids, and, 13 limit of physical subdivision and, 13 nonpolar, 127–129 polar, 127–129 triatomic, 13–14 Monoacylglycerol, use of, as emulsifiers, 621 Monoatomic ion An ion formed from a single atom through loss or gain of electrons, 98 charges on, 89–90 formulas for compounds containing, 92–93 naming compounds containing only, 94–98 Monocarboxylic acid A carboxylic acid in which one carboxyl group is present, 474 nomenclature for, 474–477 physical-state summary for, 483 Monomer The small molecule that is the structural repeating unit in a polymer, 378 types of, addition polymerization, 378–382 Monomeric protein A protein in which only one peptide chain is present, 669 Monoprotic acid An acid that supplies one proton (H⫹ ion) per molecule during an acid-base reaction, 257 examples of, 257–258 Monosaccharide A carbohydrate that contains a single polyhydroxy aldehyde or polyhydroxy ketone unit, 557 amino sugar formation from, 581–582 -aric acid formation from, 578 biochemically important, 570–574 chirality of, 562–565 classification of, by functional group, 569–570 classification of, by number of carbon atoms, 569–570 cyclic forms, formation of, 574–577 cyclic forms, Haworth projection formulas and, 576–577 disaccharide formation from, 583–587 glycoside formation from, 579, 581 hemiacetal forms of, 574–577 markers determining blood types, 580 -onic acid formation from, 578 oxidation of, 578–579 phosphate ester formation from, 581 reactions of, 577–582 reduction of, 579 sugar alcohol formation from, 579 terminology associated with, summary of, 581 -uronic acid formation from, 579

Monounsaturated fatty acid A fatty acid with a carbon chain in which one carboncarbon double bond is present, 610 common, listing of, 612 double-bond position and, 611–612 structural formula notation for, 610, 612 Morphine, 530 mRNA. See messenger RNA MTBE, use of, as gasoline additive, 426 Multimeric protein A protein in which more than one peptide chain is present, 669 Mutagen A substance or agent that causes a change in the structure of a gene, 763 selected types of, 763 Mutase, function of, 818 Mutation An error in base sequence in a gene that is reproduced during DNA replication, 763 DNA base sequence and, 763 Myoglobin biochemical function of, 681 primary structure of, 670 tertiary structure of, 679 Myosin, 682 NAD. See Nicotinamide adenine dinucleotide NADH⫹. See Nicotinamide adenine dinucleotide NADH-coenzyme Q reductase electron transport chain and, 795–796 structural characteristics of, 795–796 NADP⫹. See Nicotinamide adenine dinucleotide phosphate NADPH. See Nicotinamide adenine dinucleotide phosphate Naproxen cyclooxygenase inhibitor, 646 pharmacology of, 480 structure of, 480 Natural gas, chemical composition of, 345 Natural sugar A sugar naturally present in whole foods, 598 Network polymer A polymer in which monomers are connected in a three-dimensional cross-linked network, 463 formaldehyde-based, 463 Neurotransmitter A chemical substance that is released at the end of a nerve, travels across the synaptic gap between the nerve and another nerve, and then bonds to a receptor site on the other nerve, triggering a nerve impulse, 526 amines as, 526–528 peptide, 668 Neutral solution An aqueous solution in which the concentrations of H3O⫹ ion and OH⫺ ion are equal; an aqueous solution whose pH is 7.0, 264–265, 268 hydronium ion concentration and, 264–266 pH value and, 268 Neutralization reaction, acid–base, titration procedure for, 282, 284–285 Neutron A subatomic particle that has no charge associated with it, 52 location of, within atom, 52 properties of, 52 role of in nuclear fission, 312–313

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Index/Glossary

Niacin coenzyme functions of, 724 dietary sources of, 725 structure forms of, 723 Nicotinamide presence of, in nicotinamide adenine dinucleotide, 783–784 Nicotinamide adenine dinucleotide citric acid cycle and, 792–793 electron transport chain fuel, 794–795 ethanol fermentation and, 824 general metabolic function of, 783 lactate fermentation and, 823–824 NAD⫹ form of, 784 NADH form of, 784 oxidation deamination reactions and, 882–883 oxidized form of, 783–784 pyruvate oxidation and, 822–823 reduced form of, 783–784 structural subunits within, 783–784 Nicotinamide adenine dinucleotide phosphate oxidized form of, 834 pentose phosphate pathway and, 834 reduced form of, 834 Nicotinamide adenine mononucleotide, b oxidation pathway and, 847–849 Nicotine addiction to, 527 biochemical effects of, 527 concentration of, cigarette and, 527 influence of, prescription drugs and, 527 structural forms of, 527 Nirenberg, Marshall, 753 Nitric acid acid rain, component of, 272 esters of, 503, 505 Nitric oxide biochemical messenger functions of, 889 biochemical role of, 117 Lewis structure for, 117 production of, arginine and, 889 properties of, 117 Nitrogen, solubility of, in blood, 195 Nitrogen atom, bonding characteristics of, 514–515 Nitrogen balance The state that results when the amount of nitrogen taken into the human body as protein equals the amount of nitrogen excreted from the body in waste products, 877 negative, causes of, 877 positive, causes of, 877 Nitrogen-containing bases, nucleotide subunits, 735–736 Nitroglycerin ingredient in dynamite, 167 structure of, 505 uses for, 505 Noble gas A general name for any element in Group VIIIA of the periodic table; an element located in the far right column of the periodic table, 60, 73 electronic characteristics of, 73–74 London forces and, 186 periodic table location of, 60, 73–75 stability of electron configurations of, 87

Nomenclature acetals, 462 acyl group, 503 alcohols, 401–403 aldehydes, 445–447 alkanes, 329–335 alkenes, 363–365 alkenyl groups, 365 alkyl groups, 330, 339–340 alkynes, 382–383 amides, 533–535 amine salts, 521–523 amines, 516–518 aromatic hydrocarbons, 386–389 binary ionic compounds, 94–98 binary molecular compounds, 130–131 carboxylate ions, 484 carboxylic acid salts, 485 carboxylic acids, 474–479 common name use in, 130–131 cycloalkanes, 341–342 cycloalkenes, 363–365 disulfides, 432 enzymes, 699–703 esters, 489–491 ethers, 423–425 fatty acids, 610–612 glycosides, 579, 581 halogenated alkanes, 350–351 hemiacetals, 462 IUPAC rules and, 330–332 ketones, 447–448 lactams, 533 lactones, 491 nucleotides, 737–738 ortho-meta-para, use of, 387 phenols, 419–420 polyatomic-ion containing compounds, 101–12 quaternary ammonium salts, 524 rules summary, for ionic compounds, 102 small peptides, 666–667 substituted ammonium ions, 520–521 thioethers, 431 thiols, 429–430 Nomex, 543 Nonaqueous solution A solution in which a substance other than water is the solvent, 195 Nonbonding electrons Pairs of valence electrons on an atom that are not involved in electron sharing, 110 Noncompetitive enzyme inhibitor A molecule that decreases enzyme activity by binding to a site on an enzyme other than the active site, 711 mode of action, 711–712 Nonelectrolyte A substance whose aqueous solution does not conduct electricity, 279 characteristics of, 279–280 Non-ionizing radiation Radiation with insufficient energy to remove an electron from an atom or molecule, 303 effects of, 303 types of, 303 Nonmetal An element characterized by the absence of the properties of luster,

A-47

thermal conductivity, electrical conductivity, and malleability, 62 general properties of, 62, 75 human body composition and, 64 periodic table locations for, 63 Nonoxidation–reduction chemical reaction A chemical reaction in which there is no transfer of electrons from one reactant to another reactant, 226 Nonpolar amino acid An amino acid that contains one amino group, one carboxyl group, and a nonpolar side chain, 656 structures of, 656–657 Nonpolar covalent bond A covalent bond in which there is equal sharing of electrons between atoms, 124 electronegativity differences and, 125–126 Nonpolar molecule A molecule in which there is a symmetrical distribution of electron charge, 127 characteristics of, 127–129 Nonsuperimposable mirror image Mirror images that do not coincide at all points when the images are laid upon each other, 558 Norco, 530 Norepinephrine, neurotransmitter function of, 528 Norethynodrel, 642 Normal boiling point The temperature at which a liquid boils under a pressure of 760 mm Hg, 180 Novocaine, 536 Nuclear energy, nuclear power plants and, 313 Nuclear equation An equation in which the chemical symbols present represent atomic nuclei rather than atoms, 295 alpha-particle decay, 295–297 balancing procedures for, 295–297 beta-particle decay, 295–296 fission, 313–314 fusion, 312–313 gamma-ray emission, 296 Nuclear fission A nuclear reaction in which a large nucleus (high atomic number) splits into two medium-sized nuclei, with the release of several free neutrons and a large amount of energy, 312 characteristics of, 312–313 nuclear power plants and, 313 uranium-235 and, 312–313 Nuclear fusion A nuclear reaction in which two small nuclei are put together to make a larger one, 313 occurrence on the sun, 314 Nuclear medicine A field of medicine in which radionuclides are used for diagnostic and therapeutic purposes, 309 diagnostic uses, 310–311 therapeutic uses, 312 Nuclear power plants, 313 Nuclear reaction A reaction in which changes occur in the nucleus of an atom, 292 bombardment, 300 characteristics for, 315 contrasted with chemical reaction, 316 fission, 312–313 fusion, 313–315 radioactive decay, equations for, 295–297

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A-48

Index/Glossary

Nuclear weapons, 313–314 Nucleic acid A polymer in which the monomer units are nucleotides, 734 backbone of, 739 directionality of structure of, 740 nucleotides within, 735–736 primary structure of, 738–740 types of, 734 Nucleon Any subatomic particle found in the nucleus of an atom, 52 types of, 52 Nucleotide A three-subunit molecule in which a pentose sugar is bonded to both a phosphate group and a nitrogen-containing heterocylic base, 735 formation of, 736–737 nitrogen-containing base subunit of, 735–736 nomenclature for, 737–738 pentose sugar subunit of, 735 phosphate subunit of, 736 structural subunits of, 735–736 synthetic, medical uses for, 738 Nucleus The small, dense, positively charged center of an atom, 52 protons and neutrons with, 52 size of, relative to whole atom, 52 stability of, factors affecting, 293 Nuclide An atom with a specific atomic number and a specific mass number, 292 daughter, 295–297 parent, 295–297 radioactive, 293 stable, 293 unstable, 293 Number exact, 26 inexact, 26 Nutrient protein, 683 Nylon, 542 Octet rule In forming compounds, atoms of elements lose, gain, or share electrons in such a way as to produce a noble-gas electron configuration for each of the atoms involved, 87 covalent bond formation and, 109–111 ions and, 89–90 valence electron configurations and, 87 Odor, chemical sense of, relationship to molecular geometry, 122 Oil A triacylglycerol mixture that is a liquid at room temperature, 617 chemical reactions of 621–629 dietary considerations and, 618–621 general properties of, 616–618 lipid, 617 lipid-petroleum comparison, 617 olive, 618 partial hydrogenation of, 625–626 petroleum, 617 property-contrast with fats, 617–618 rancidity of, 627 Okazaki fragments, DNA replication and, 745–746 Olefin, 362 Olestra, 624

Oligosaccharide A carbohydrate that contains two to ten monosaccharide units covalently bonded to each other, 557 Olive oil, pharmacological activity of, 618 Omega-3 fatty acid An unsaturated fatty acid with its endmost double bond three carbon atoms away from its methyl end, 611 dietary sources of, 619 examples of, 611–612 Omega-6 fatty acid An unsaturated fatty acid with its endmost double bond six carbon atoms away from its methyl end, 611 dietary sources of, 619 examples of, 611–612 Onion odiferous compounds present, 432 sulfur-containing compounds and, 432 tear production and, 449 Optically active compound A compound that rotates the plane of polarized light, 567 types of, 567–568 Optimum pH The pH at which an enzyme exhibits maximum activity, 706 Optimum temperature The temperature at which an enzyme exhibits maximum activity, 706 Orbital diagram A diagram that shows how many electrons an atom has in each of its occupied electron orbitals, 68 interpretation of, 68–69 procedures for writing, 68–69 Organelle A minute structure within the cytoplasm of a cell that carries out a specific cellular function, 779 types of, 779 Organic chemistry The study of hydrocarbons and their derivatives, 322 contrasted with inorganic chemistry, 322 subdivisions within, 322–323 Ornithine structure of, 884 urea cycle and, 884–887 Ortho-, prefix, meaning of, 387 Osmolarity The product of a solution’s molarity and the number of particles produced per formula unit if the solute dissociates, 212 calculations involving, 212–213 mathematical equation for, 212 Osmosis The passage of solvent through a semipermeable membrane separating a dilute solution (or pure solvent) from a more concentrated solution, 210 kinetic molecular theory and, 211 process of, description of, 210–211 relationship to dialysis, 215–216 Osmotic pressure The pressure that must be applied to prevent the net flow of solvent through a semipermeable membrane from a solution of lower concentration to a solution of higher concentration, 211–212 biochemical importance of, 212 factors affecting, 212–213 measurement of, 212 osmolarity and, 212–213 terminology associated with, 212–214

Oxaloacetate amino acid biosynthesis from, 891 amino acid degradation product, 890 citric acid cycle and, 789–790, 792, 794 gluconeogenesis and, 828–829 ketone body formation and, 854 Oxaloacetic acid, 482–483 Oxidation The process whereby a reactant in a chemical reaction loses one or more electrons, 230 electron-based definition for, 230–231 organic compounds, operational definition for, 415 oxidation number-based definition for, 230–231 rancidity of fats and oils and, 627 Oxidation number A number that represents the charge that an atom appears to have when the electrons in each bond it is participating in are assigned to the more electronegative of the two atoms involved in the bond, 226 determining, example of, 228–229 rules for determining, 226–229 Oxidation–reduction chemical reaction A chemical reaction in which there is a transfer of electrons from one reactant to another reactant, 226 naturally occurring corrosion processes, 232 terminology associated with, 230–232 Oxidative deamination reaction A biochemical reaction in which an alpha-amino acid is converted into an a-keto acid with release of an ammonium ion, 882 ammonium ion production and, 882–883 Oxidative phosphorylation The biochemical process by which ATP is synthesized from ADP as a result of the transfer of electrons and hydrogen ions from NADH and FADH2 to O2 through the electron carriers of the electron transport chain, 800 ATP production and, 800–802 chemiosmotic coupling and, 801–802 electron transport chain and, 800–802 Oxidizing agent The reactant in a redox reaction that causes oxidation of another reactant by accepting electrons from it, 231 identification of, 231–232 Oxidoreductase An enzyme that catalyzes an oxidation–reduction reaction, 700 examples of, 700, 702 Oxycodone, 530, 532 Oxygen electron transport chain consumption of, 798–799 hemoglobin catabolism and, 893 lipogenesis and, 864 non-ETC consumption of, 804–806 solubility of, in water, 195 Oxygen atom, bonding characteristics of, 399–400 Oxytocin, 667–668 Ozone depletion of, ozone hole and, 240 stratospheric concentrations of, 240

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Index/Glossary

Ozone hole chlorofluorocarbons and, 240 nature of, 240 Ozone layer, chlorofluorocarbons and, 351 Pantothenic acid coenzyme functions of, 724 dietary sources of, 725 presence of, in coenzyme A, 784–785 structure of, 723 Para-, prefix, meaning of, 387 Paraffin, 348 Parent nuclide The nuclide that undergoes decay in a radioactive decay process, 295 Partial pressure The pressure that a gas in a mixture of gases would exert if it were present alone under the same conditions, 174 use of, in calculations, 174 Passive transport The transport process in which a substance moves across a cell membrane by diffusion from a region of higher concentration to a region of lower concentration without the expenditure of cellular energy, 639 process of, characteristics for, 639–640 Pauling, Linus Carl, 123 PEN, condensation polymer, properties of, 500 Penicillins mode of action, 716–717 Pentose phosphate pathway The metabolic pathway by which glucose is used to produce NADPH, ribose 5-phosphate (a pentose phosphate), and numerous other sugar phosphates, 833 nonoxidative stage of, 834 oxidative stage of, 834 purposes for, 834 Pentose sugar, as nucleotide subunit, 735 Pepcid, 265 Peptide An unbranched chain of amino acids, each joined to the next by a peptide bond, 664 antioxidant function for, 668 backbone of, 665 biochemical functions of, 666–667 directionality of, 664 enkephalins, 668 glutathione, 668 hormone function for, 666–667 isomeric forms of, 667 neurotransmitter function for, 668 oxytocin, 667–668 peptide bonds within, 664 small, nomenclature for, 666–667 structural formulas of, 665–666 vasopressin, 667–668 Peptide bond A covalent bond between the carboxyl group of one amino acid and the amino group of another amino acid, 664 Percent by mass The mass of solute in a solution divided by the total mass of solution, multiplied by 100, 198 calculations involving, 199–200 mathematical equation for, 198 Percent by volume The volume of solute in a solution divided by the total volume of solution, multiplied by 100, 200

mathemtical equation for, 200 Percent elemental composition by mass, 58–59 by number of atoms, 58–59 Percocet, 530 Percodan, 530 Period A horizontal row of elements in the periodic table, 59 in periodic table, notation for, 59–60 Periodic law When elements are arranged in order of increasing atomic number, elements with similar chemical properties occur at periodic (regularly recurring) intervals, 59 discovery of, 59 electron configurations and, 71–72 visual representation of, 59–61 Periodic table A tabular arrangement of the elements in order of increasing atomic number such that elements having similar chemical properties are positioned in vertical columns, 59 atomic number sequence within, 61 classification systems for elements and, 73–75 distinguishing electrons and, 72–73 electron configurations and element location, 72–73 groups within, 60 information shown on, 59 long form of, 61 metals, location for, 63 most common form of, 60 nonmetals, location for, 63 periods within, 59–60 shape of, rationale for, 71–72 specifying element position within, 59–60 Peripheral membrane protein A nonpenetrating membrane protein located on the surface of the cell membrane, 638 Peroxides, from ethers, 426 PET, condensation polymer, properties of, 499–500 Petrolatum, 348 Petroleum chemical composition of, 345 refining of, 345 pH The negative logarithm of an aqueous solution’s molar hydronium ion concentration, 266 calculations involving, 268 effect on zwitterion structure, 660–661 enzyme activity and, 706–707 integral values, calculation of, 266–267 mathematical expression for, 266 measurement of, 269 nonintegral values, calculation of, 267–268 optimum, for enzymes, 706–707 relationship to hydronium and hydroxide concentration, 268 values of, for aqueous salt solutions, 270–274 values of, for selected common substances, 269 values of, significant figures and, 266 pH scale A scale of small numbers used to specify molar hydrogen ion concentrations in aqueous solution, 266

A-49

interpreting values on, 268–269 PHBV, condensation polymer, properties of, 500 Phenol An organic compound in which an -OH group is attached to a carbon atom that is part of an aromatic ring system, 419 acidity of, 420–421 antioxidant properties of, 421–422 chemical reactions of, 420–421 general formula for, 419 naturally occurring, 421–422 nomenclature for, 419–420 physical properties of, 420 structural characteristics of, 419 uses for, 421–422 Phenoxide ion, 420–421 Phenylalanine, PKU and, 892 Pheromone A compound used by insects (and some animals) to transmit a message to other members of the same species, 370 alkene, 370–371 ester, 492 Phosphatase, function of, 829 Phosphate, nucleotide subunit, 736 Phosphate ester An organic compound formed from the reaction of an alcohol with phosphoric acid, 504 examples of, 504 formation of, from cyclic monosaccharides, 581 Phosphate fertilizer, sulfuric acid and, 156 Phosphatidyl group, 630 Phosphatidylcholines, 630, 632 Phosphatidylethanolamines, 630, 632 Phosphatidylserines, 630, 632 Phosphoanhydride bond A chemical bond formed when two phosphate groups react with each other and a water molecule is produced, 781 adenosine phosphates and, 781 Phosphoenolpyruvate gluconeogenesis and, 830–831 glycolysis and, 818 2-Phosphoglycerate, glycolysis and, 818 3-Phosphoglycerate amino acid biosynthesis from, 891 glycolysis and, 817–818 Phospholipid A lipid that contains one or more fatty acids, a phosphate group, a platform molecule to which the fatty acids and phosphate group are attached, and an alcohol that is attached to the phosphate group, 629 biochemical functions of, 631 generalized structure of, 629 summary diagram, types of, 634 types of, 629 Phosphoric acid anhydrides of, 504–505 biochemically important forms, 504–505 esters of, 503–505 Phosphoric acid anhydride, 504–505 Phosphoryl group A functional group derived from a phosphate ion that is part of another molecule, 781 adenosine phosphates and, 781

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Index/Glossary

Phosphorylase, function of, 829 Phosphorylation oxidative, 800–802 substrate-level, 818 Photosynthesis, carbohydrates and, 556 Phylloquinones, 728 Physical, use of the term, 5–6 Physical change A process in which a substance changes its physical appearance but not its chemical composition, 4 characteristics of, 4–5 state changes and, 4 Physical property A characteristic of a substance that can be observed without changing the basic identity of the substance, 2 examples of, 2–4 of matter, 2 temperature and pressure dependence of, 2 Physical subdivision, limit of, 13 Phytochemicals, 805 pKa calculation of, 269–270 carboxylic acids, values for, 484 definition of, 267 Plane-polarized light, 567 Plasma, state of matter, 314 Plasma lipoprotein A lipoprotein that is involved in the transport system for lipids in the bloodstream, 689 types of, 690–691 Plasma membrane, 637 Plasmid, recombinant DNA production and, 766–767 Poison ivy, 422 Polar acidic amino acid An amino acid that contains one amino group and two carboxyl groups, the second carboxyl group being part of the side chain, 656 structures of, 656–657 Polar basic amino acid An amino acid that contains two amino groups and one carboxyl group, the second amino group being part of the side chain, 656 structures of, 656–657 Polar covalent bond A covalent bond in which there is unequal sharing of electrons between two atoms, 125 electronegativity differences and, 125–126 Polar molecule A molecule in which there is an unsymmetrical distribution of electron charge, 127 characteristics of, 127–129 Polar neutral amino acid An amino acid that contains one amino group, one carboxyl group, and a side chain that is polar but neutral, 656 structures of, 656–657 Polarimeter, components of, 567 Polarity chemical bonds and, 124–126 molecular, 126–129 solubility of solutes and, 197–198 solubility of vitamins and, 199 Polyamide A condensation polymer in which the monomers are joined through amide linkages, 542

Kelvar, 542–543 Nomex, 543 nylon, 542 silk, 543 wool, 543 Polyatomic ion An ion formed from a group of atoms (held together by covalent bonds) through loss or gain of electrons, 98 common, listing of, 99 formula writing conventions for compounds containing, 100–101 formulas for compounds containing, 100–101 generalizations about formulas for, 99 Lewis structures for, 117–118 naming compounds containing, 101–102 tooth enamel and, 100 Polyester A condensation polymer in which the monomers are joined through ester linkages, 499 examples of, 499–500 PEN, properties of, 500 PET, properties of, 499–500 PHBV, properties of, 500 Polyethylene, 379–380 Polyfunctional carboxylic acid A carboxylic acid that contains one or more additional functional groups besides one or more carboxyl groups, 474 hydroxy, 479–481 keto, 481 metabolic, 482–483 types of, 479–481 unsaturated, 479 Polyisoprene, 381 Polymer A large molecule formed by the repetitive bonding together of many smaller molecules, 378 addition, 378–382 alcohol, 418–419 condensation, 499–500 formaldehyde-based, 463 network, 463 polyamides, 542–544 polyesters, 499–500 polyurethanes, 544–545 Polymerase chain reaction (PCR) A method for rapidly producing multiple copies of a DNA nucleotide sequence, 768 cyclic nature of, 768–769 primer and, 768–769 steps in, 768–769 Polymerization reaction A chemical reaction in which the repetitious combining of many small molecules (monomers) produces a very large molecule (the polymer), 378 Polypeptide A long unbranched chain of amino acids, each joined to the next by a peptide bond, 664 backbone of, 665 contrasted with protein, 668–669 Polypropylene, 379–380 Polyprotic acid An acid that supplies two or more protons (H⫹ ions) per molecule in an acid-base reaction, 257 step-wise dissociation of, 257, 261

Polyribosome A complex of mRNA and several ribosomes, 762 formation of, protein synthesis and, 762 Polysaccharide A polymeric carbohydrate that contains many monosaccharide units covalently bonded to each other by glycosidic linkages, 557, 587 acidic, 595–596 general characteristics of, 587, 589–590 general types of, 587, 589–591 storage, 591–593 structural, 593–594 Polysome, 762 Polystyrene, 380 Polyunsaturated fatty acid A fatty acid with a carbon chain in which two or more carbon–carbon double bonds are present, 610 common, listing of, 612 double-bond position and, 612 structural formula notation for, 611–612 Polyurethane A polymer formed from the reaction of dialcohol and diisocyanate monomers, 544 preparation reaction for, 544 Spandex, 544 structural characteristics of, 544 Poly(vinyl alcohol), 418–419 Poly(vinyl chloride), 380 Popcorn, popping of, 167 Positional isomers Constitutional isomers with the same carbon-chain arrangement but different hydrogen atom arrangements as the result of differing location of the functional group present, 366 alcohol, 403 alkene, 366 alkyne, 383 ester, 493 ketone, 450 Post-translation processing, important aspects of, 762 Potential energy Stored energy that matter possesses as a result of its position, condition, and/or chemical composition, 164 cohesive forces and, 164–166 electrostatic interactions and, 164 kinetic molecular theory of matter and, 164–166 Prednisolone, 643 Pressure The force applied per unit area on an object; the force on a surface divided by the area of that surface, 167 boiling point magnitude and, 180–181 measurement of, using barometer, 168 partial, 173–175 significant figures and measurement of, 168 solubility of solutes and, 194 units for, 168 Primary alcohol An alcohol in which the hydroxyl-bearing carbon atom is bonded to only one other carbon atom, 410 hydrogen bonding and, 410 structural characteristics of, 410 Primary amide An amide in which two hydrogen atoms are bonded to the amide nitrogen atom, 532

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Index/Glossary

Primary amine An amine in which the nitrogen atom is bonded to one hydrocarbon group and two hydrogen atoms, 515 Primary carbon atom A carbon atom in an organic molecule that is bonded to only one other carbon atom, 338 Primary nucleic acid structure The sequence in which nucleotides are linked together in a nucleic acid, 739 contrasted with primary protein structure, 739 general characteristics of, 738–740 Primary protein structure The order in which amino acids are linked together in a protein, 670 contrasted with primary nucleic acid structure, 739 insulin, 671, 675 myoglobin, 670 Primary transcript RNA, 747 Primer DNA sequencing and, 770 polymerase chain reaction and, 768–769 Procaine, 536 Product A substance produced as a result of a chemical reaction, 146 location of, in a chemical equation, 146 Proenzyme, 714 Progesterone, 642 Progestins biochemical functions of, 642 synthesis of, from cholesterol, 869 Project ENCODE human genome and, 752 purpose of, 752 Propanoic acid derivatives, antimicrobial action of, 486 derivatives, metabolic functions for, 482–483 derivatives, pain-relief from, 480 Property A distinguishing characteristic of a substance that is used in its identification and description, 2 chemical, 2–4 colligative, 209–215 physical, 2–4 types of, 2–4 Propanoate, derivatives of, transamination and, 879 Propofol, 422 Propylene glycol properties of, 406 uses for, 406 Prostaglandin A messenger lipid that is a C20-fatty-acid derivative that contains a cyclopentane ring and oxygen-containing functional groups, 645 biochemical functions of, 645 structural characteristics of, 645 Prosthetic group A non-amino-acid group permanently associated with a protein, 669 conjugated proteins and, 669 Protective-coating lipid, biological wax, 646–648 Protein A biochemical polymer in which the monomer units are amino acids; a

polypeptide in which at least 40 amino acid residues are present, 655, 668 actin, 682 amino acid building blocks of, 656–657 catalytic, 682 classification of, by function, 682–683 classification of, by shape, 679–681 collagen, 680–681 complete dietary, 658 components of cell membranes, 638 conjugated, examples of, table, 669 conjugated, prosthetic groups and, 669 contractile, 683 contrasted with polypeptide, 668–669 defense, 683 denaturating agents for, 684–686 denaturation, human hair and, 686 fibrous, 679–681 general characteristics of, 655 general structural characteristics of, 669 globular, 679, 681 hemoglobin, 678, 681 human hair, 686 hydrolysis of, 683–684 a-keratin, 680 membrane, integral, 638 membrane, peripheral, 638 membrane, types of, 638–639 messenger, 683 monomeric, 669 multimeric, 669 myoglobin, 670, 678, 681 myosin, 682 nutrient, 683 primary structure of, 670–671 regulatory, 683 secondary structure, alpha helix, 672–674 secondary structure, beta-pleated sheet, 672–674 secondary structure, unstructured segments, 673–674 simple, 669 storage, 683 structural, 683 structure-summary for, 678 tertiary structure, disulfide bonds, 675 tertiary structure, electrostatic interactions, 675–676 tertiary structure, hydrogen bonding, 675–676 tertiary structure, hydrophobic attractions, 676 tertiary structure, salt bridges, 675 transmembrane, 683 transport, 683 Protein denaturation The partial or complete disorganization of a protein’s characteristic three-dimensional shape as a result of disruption of its secondary, tertiary, and quaternary structural interactions, 684 examples of, 684–685 Protein digestion enzymes needed for, 875–876 locations for, within human body, 875–876 products from, 875–876 steps in, 875–876

A-51

Protein metabolism relationship between carbohydrate metabolism and, 895–897 relationship between lipid metabolism and, 895–897 Protein structure color of meat and, 682 levels of, 669–678 Protein synthesis inhibition of, antibiotics and, 761 overview of, 747 post-translation processing and, 762 site for, ribosomal RNA and, 758 summary-diagram of, 764 transcription phase of, 749–752 translation phase of, 758–762 Protein turnover The repetitive process in which proteins are degraded and resynthesized within the human body, 877 causes of, 877 Proteolytic enzyme An enzyme that catalyzes the breaking of peptide bonds that maintain the primary structure of a protein, 714 Protium, hydrogen isotope, 55 Proton A subatomic particle that possesses a positive electrical charge, 51 location of, within atom, 52 nuclear charge and, 52 properties of, 51–52 Prozac, 528 Pure substance A single kind of matter that cannot be separated into other kinds of matter by any physical means, 6 characteristics of, 6–9 compounds as, 6–9 elements as, 6–9 types of, 6–9 Purine, derivatives of, nucleotides and, 735–737 Pyran, 428 Pyridoxal phosphate, transamination reactions and 880–881 Pyrimidine, derivatives of, nucleotides and, 735, 737 Pyruvate amino acid biosynthesis from, 891 amino acid degradation product, 890 Cori cycle and, 832 fates of, 822–826 gluconeogenesis and, 830–831 glycolysis and, 818 oxidation to acetyl CoA, 822–823 reduction to ethanol, 824 reduction to lactate, 823–824 Pyruvic acid, 481–483 Quaternary ammonium salt An ammonium salt in which all four groups attached to the nitrogen atom of the ammonium ion are hydrocarbon groups, 524 nomenclature of, 524 properties of, 524 Quaternary carbon atom A carbon atom in an organic molecule that is bonded to four other carbon atoms, 339

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A-52

Index/Glossary

Quaternary protein structure The organization among the various polypeptide chains in a multimeric protein, 677 hemoglobin, 678 interactions responsible for, 677 Quercetin, 805 Quinine, 529 Radiation background levels for, 308 biochemical effects of, 305–306 chemical effects of, 302–304 detection of, 306–307 exposure to, sources of, 307–309 ionizing, 303–304 nonionizing, 303 use of, in food preservation, 307 use of, in medicine, 309–312 Radioactive decay The process whereby a radionuclide is transformed into a nuclide of another element as a result of the emission of radiation from its nucleus, 295 alpha particle emission, 295 beta particle emission, 295–296 equations for, 295–297 gamma ray emission, 296 rate of, 297–300 summary diagram for, 299 types of, 295–297 Radioactive decay series A series of radioactive decay processes beginning with a longlived radionuclide and ending with a stable nuclide of lower atomic number, 302 example of, 302 Radioactive nuclide A nuclide with an unstable nucleus from which radiation is spontaneously emitted, 293 factors affecting nuclear stability and, 293 laboratory-production of, 300–301 natural occurance of, 293, 301 parent and daughter, 295 types of decay for, 295–296 use of, in medicine, 309–312 Radioactivity The radiation spontaneously emitted from an unstable nucleus, 293 discovery of, 293–294 nature of emissions, 293–294 Radon cigarette smoking and, 303 decay series intermediate, 303 exposure sources for, 308–309 indoor radon-222 problem, 309 Rancidity antioxidants and, 627 fatty acid oxidation and, 627 Reactant A starting substance in a chemical reaction that undergoes change in the chemical reaction, 146 location of, in a chemcal equation, 146 Reactive oxygen species formation of, 805–806 hydrogen peroxide, 805–806 hydroxyl free radical, 805–806 superoxide ion, 805–806 Recombinant DNA (rDNA) DNA that contains genetic material from two different organisms, 766

clones and, 767–768 E. coli bacteria use and, 766 plasmids and, 766–767 steps in formation of, 766–767 substances produced using, table of, 765 therapuetic medicine and, 765 transformation process and, 765–768 Recycling, addition polymers and, 380–381 Reducing agent The reactant in a redox reaction that causes reduction of another reactant by providing electrons for the other reactant to accept, 231 identification of, 231–232 Reducing sugar A carbohydrate that gives a positive test with Tollens and Benedict’s solutions, 578 characteristics of, 578 disaccharide, 583–587 monosaccharide, 578 Reduction The process whereby a reactant in a chemical reaction gains one or more electrons, 230 electron-based definition for, 230–231 organic compounds, operational definition for, 415 oxidation number-based definition for, 230–231 Refined sugar A sugar that has been separated from its plant source, 598 Regulatory protein, 683 Representative element An element located in the s area or the first five columns of the p area of the periodic table, 74 electronic characteristics of, 74–75 periodic table location of, 74–75 Resorcinol, 420 Restriction enzyme An enzyme that recognizes specific base sequences in DNA and cleaves the DNA in a predictable manner at these sequences, 767 DNA sequencing and, 770 recombinant DNA production and, 766–767 Retrovirus, 765 AIDS virus as a, 765 Reversible chemical reaction A chemical reaction in which the conversion of reactants to products (the forward reaction) and the conversion of products to reactants (the reverse reaction) occur simultaneously, 238 Reversible competitive inhibitor, 710–712 Reversible noncompetitive inhibitor, 711–712 Ribitol, presence of, in flavin adenine dinucleotide, 782 Riboflavin coenzyme functions of, 724 dietary sources of, 725 presence of, in flavin adenine dinucleotide, 782 structure of, 723 Ribonucleic acid (RNA) A nucleotide polymer in which each of the monomers contains ribose, phosphate, and one of the heterocyclic bases adenine, cytosine, guanine, or thymine, 738 abundances of, 748 backbone of, structure for, 739 differences between DNA and, 747

functions for, 747–749 synthesis of, transcription and, 749–752 types of, 747–749 Ribose as nucleotide subunit, 735 occurrence of, 574 phosphorylated, 784–785 presence of, in flavin adenine dinucleotide, 782 presence of, in nicotinamide adenine dinucleotide, 783–784 structure of, 573 Ribose 5-phosphate, pentose phosphate pathway and, 834 Ribosomal RNA (rRNA) RNA that combines with specific proteins to form ribosomes, the physical sites for protein synthesis, 749 protein synthesis site and, 758 Ribosome An rRNA-protein complex that serves as the site for the translation phase of protein synthesis, 758 biochemical functions for, 758, 779 presence of, in cells, 779 structural characteristics of, 758 translocation and, 759–761 Ribozyme, 758 Ribulose 5-phosphate pentose phosphate pathway and, 834 RNA. See ribonucleic acid RNA polymerase, 750 ROS. See Reactive oxygen species Rounding off The process of deleting unwanted (nonsignificant) digits from calculated numbers, 29 of numbers, rules for, 29 rRNA. See Ribosomal RNA RU-486, 642 Rubber natural, 381 synthetic, 382 Rubbing alcohol, 405 Rutherford, Ernest, 294, 300 Saccharin, 590 Salicylic acid, 492–494 Salt An ionic compound containing a metal or polyatomic ion as the positive ion and a nonmetal or polyatomic ion (except hydroxide ion) as the negative ion, 261 acid–base “parentage” of, 270–274 acid–base neutralization, formation of and, 262–263 amine, 521–523 carboxylic acid, 484–486 dissociation of, in solution, 262 hydrolysis of, 270–274 quaternary ammonium, 524–525 Salt bridge, protein tertiary structure and, 675 Sanger, Frederick, 670 Saponification reaction The hydrolysis of an organic compound, under basic conditions, in which a carboxylic acid salt is one of the products, 496 amides, 540–541 esters, 496–497 triacylglycerols, 623–625 Saran, 380–381

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Index/Glossary

Saturated carbon atom, 400 Saturated fatty acid A fatty acid with a carbon chain in which all carbon–carbon bonds are single bonds, 610 common, listing of, 612 structural formula notation for, 610, 612 Saturated hydrocarbon A hydrocarbon in which all carbon–carbon bonds are single bonds, 323 alkanes, 323–340 cycloalkanes, 340–344 Saturated solution A solution that contains the maximum amount of solute that can be dissolved under the conditions at which the solution exists, 194 characteristics of, 194 Scientific notation A numerical system in which numbers are expressed in the form A 3 10n. where A is a number with a single nonzero digit to the left of the decimal place and n is a whole number, 32 coefficients in, 32 converting to, from decimal notation, 32 division in, 33–34 exponents in, 32 multiplication in, 33–34 significant figures and, 33 uncertainty and, determination of, 34 use of, for numbers, 32 Secondary alcohol An alcohol in which the hydroxyl-bearing carbon atom is bonded to two other carbon atoms, 410 hydrogen bonding and, 410 structural characteristics of, 410 Secondary amide An amide in which an alkyl (or aryl) group and a hydrogen atom are bonded to the amide nitrogen atom, 532 Secondary amine An amine in which the nitrogen atom is bonded to two hydrocarbon groups and one hydrogen atom, 515 Secondary carbon atom A carbon atom in an organic molecule that is bonded to two other carbon atoms, 338 Secondary protein structure The arrangement in space adopted by the backbone portion of a protein, 671 alpha helix, 672 beta pleated sheet, 672–674 interactions responsible for, 671–672 peptide bond geometry, 671–672 types of, 671–674 unstructured segments within, 673–674 Semipermeable membrane A membrane that allows certain types of molecules to pass through it but prohibits the passage of other types of molecules, 210 characteristics of, 210 Serotonin lactation and, 528 neurotransmsitter function of, 528 Sevoflurane, 425 Shuttle system carnitine/acyl-carnitine, 847 citrate-malate, 859 dihydroxyacetone/glycerol 3-phosphate, 826–827 fatty acid transport and, 847

lipogenesis and acetyl CoA, 859 NADH from glycolysis and, 826–827 Significant figures The digits in a measurement that are known with certainty plus one digit that is estimated, 26 addition and subtraction, 30–31 exact numbers and, 31 guidelines for determining number of, 27–28 logarithms and, 266 mathematical operations and, 28–31 multiplication and division, 30–31 pressure measurement and, 168 rounding off, to specified number of, 29 scientific notation and, 33 temperature measurement and, 43 Silk, 543 Silver, corrosion of, 232 Simple carbohydrate A dietary monosaccharide or a dietary disaccharide, 597 Simple enzyme An enzyme composed only of protein (amino acid residues), 699 Simple protein A protein that consists solely of amino acid residues, 669 Simple triacylglycerol A triester formed from the esterification of glycerol with three identical fatty acid molecules, 615–616 structural formula for, 615 Simplesse, 624 Single covalent bond A covalent bond in which two atoms share one pair of electrons, 111 molecules containing, examples of, 110–111 notation for, 112 relative strength of, 111–112 Single-replacement reaction A chemical reaction in which an atom or molecule replaces an atom or group of atoms in a compound, 224 examples of, 224–225 general equation for, 224 Skeletal isomers Constitutional isomers that have different carbon-chain arrangements as well as different hydrogen atom arrangements, 367 alcohol, 403 aldehyde, 450 alkene, 367 alkyne, 383 carboxylic acid, 493 Skeletal structural formula A structural formula that shows the arrangement and bonding of carbon atoms present in an organic molecule but which does not show the hydrogen atoms attached to the carbon atoms, 326 interpretation guidelines for, 326 Skin care of, carboxylic acids and, 481 sunburn of, 452 Small nuclear ribonucleoprotein particle (snRNP) A complex formed from an snRNA molecule and several proteins, 752 Small nuclear RNA (snRNA) RNA that facilitates the conversion of heterogeneous nuclear RNA to messenger RNA, 749 snRNP and, 752 spliceosomes and, 752

A-53

snRNA. See small nuclear RNA snRNP. See small nuclear ribonucleoprotein particle Soap cleansing action of, 625 making of, 624 Sodium cyclamate, 590 Solid The physical state characterized by a definite shape and a definite volume; the physical state characterized by a dominance of potential energy (cohesive forces) over kinetic energy (disruptive forces), 2, 165 distinguishing characteristics for, 2, 164 kinetic molecular theory of matter applied to, 165 melting of, 176–177 sublimation of, 176–177 Solubility The maximum amount of solute that will dissolve in a given amount of solvent under a given set of conditions, 193 controlled-release drugs and, 206 gases, factors affecting, 194 Henry’s law and, 194 rules for, 197–198 temperature and, for selected solutes, 194 terminology associated with, 194–195 values of, for selected solutes, 194 Solubility rules, for solutes, 197–198 Solute A component of a solution that is present in a lesser amount relative to that of the solvent, 192 general characteristics of, 192–193 ionic, dissolving process for, 196–197 solubility rules for, 197–198 Solution A homogeneous mixture of two or more substances with each substance retaining its own chemical identity, 192 acidic, 264–265, 268 alkaline, 264 aqueous, 195–196 basic, 264–265, 268 colligative properties of, 208–215 concentrated, 195 concentration units for, 198–205 dilute, 195 dilution of, 205–208 factors affecting rate of formation, 196–197 formation of, ionic solutes and, 196–197 general characteristics of, 192–193 hypertonic, 214–215 hypotonic, 214–215 isotonic, 214–215 neutral, 264–265, 268 nonaqueous, 196 pH of, 266–269 saturated, 194 solubility rules for solutes, 197–198 supersaturated, 194 true, characteristics of, 208 types of, 194–196 unsaturated, 194 Solvent The component of a solution that is present in the greatest amount, 192 general characteristics of, 192–193 Sorbic acid, derivatives, antimicrobial action of, 486

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A-54

Index/Glossary

Spandex, 544 Specific heat The quantity of heat energy, in calories, necessary to raise the temperature of 1 gram of a substance by 1 degree Celsius, 43 temperature change and, 43–44 use of, in calculations, 44–45 values for, table of, 43 Sphingoglycolipid A lipid that contains both a fatty acid and a carbohydrate component attached to a sphingosine molecule, 634 biochemical functions for, 634–635 cerebrosides, 635 gangliosides, 635 generalized structure for, 634 Sphingolipid, summary diagram, types of, 634 Sphingomyelins, 633 Sphingophospholipid A lipid that contains one fatty acid and one phosphate group attached to a sphingosine molecule and an alcohol attached to the phosphate group, 632–633 biochemical functions of, 633 generalized structure for, 633 sphingomyelins, 633 Sphingosine, 632–633 Spliceosome A large assembly of snRNA molecules and proteins involved in the conversion of hnRNA molecules to mRNA molecules, 752 snRNA and, 752 snRNP and, 752 Splicing The process of removing introns from a hnRNA molecule and joining the remaining exons together to form a mRNA molecule, 751 alternative, 752 Squalene, cholesterol biosynthesis and, 866 Stable nuclide A nuclide with a stable nucleus, a nucleus that does not readily undergo change, 293 Standard amino acid One of the 20 alphaamino acids normally found in proteins, 656 names and abbreviations for, 657 structures of, 657 Starch amylopectin form of, 591–592 amylose form of, 591 animal, 592 hydrolysis of, 591 iodine test and, 591 properties of, 591 structure of, 591–592 State gaseous, 2 liquid, 2 solid, 2 Statins, cholesterol levels and, 867 Stercobilin, bile pigment, 894–895 Stereoisomers Isomers that have the same molecular and structural formulas but different orientations of atoms in space, 343, 560 cis–trans, 343–344 conditions necessary for, 560–561

diastereomers as, 561 enantiomers as, 561 types of, 561 Steroid A lipid whose structure is based on a fused-ring system that involves three 6-membered rings and one 5-membered ring, 635 athletes and, 643 bile acids as, 640–641 cholesterol as, 635–636 hormones as, 641–643 structural characteristics of, 635 synthetic, 642–643 Steroid hormone A hormone that is a cholesterol derivative, 642 oral contraceptives and, 643 types of, 642–643 Steroid nucleus, 635 Storage polysaccharide A polysaccharide that is a storage form for monosaccharides and that is used as an energy source in cells, 591 glycogen, 592–593 starch, 591–592 Storage protein, 683 Strained bond, free energy considerations and, 786–788 Strong acid An acid that transfers 100%, or very nearly 100%, of its protons (H⫹ ions) to water when in an aqueous solution, 258–259 commonly encountered, 257 Strong base, commonly encountered, 259 Strong electrolyte A substance that completely (or almost completely) ionizes/ dissociates into ions in aqueous solution, 279 characteristics of, 279–280 Structural formula A two-dimensional structural representation that shows how the various atoms in a molecule are bonded to each other, 324 alkane, generation of from name, 333–334 condensed, 324 expanded, 324 line-angle, 335–337 linear, 329 skeletal, 326 Structural polysaccharide A polysaccharide that serves as a structural element in plant cell walls and animal exoskeletons, 593 cellulose, 593–594 chitin, 594 Structural protein, 683 Styrene, 386 Subatomic particle A very small particle that is a building block for atoms, 51 arrangement of, within atom, 52 properties, table of, 52 types of, 51–52 Sublimation, process of, 176–177 Substance, use of the term, 6 Substituent An atom or group of atoms attached to a chain (or ring) of carbon atoms, 329–330 alkyl, 330

Substituted ammonium ion An ammonium ion in which one or more alkyl, cycloalkyl, or aryl groups have been substituted for hydrogen atoms, 520 generalizations concerning, 520 nomenclature for, 520–521 Substitution reaction A chemical reaction in which part of a small reacting molecule replaces an atom or a group of atoms on a hydrocarbon or hydrocarbon derivative, 347–348 alkane, 347–348 aromatic hydrocarbon 390 Substrate The reactant in an enzymecatalyzed reaction, 699 Substrate-level phosphorylation The biochemical process by which a high-energy phosphate group from an intermediate compound (substrate) is directly transferred to ADP to produce ATP, 818 compared to oxidative phosphorylation, 818 glycolysis and, 818 Succinate citric acid cycle and, 791–792, 794 derivatives of, transamination and, 879 Succinate-coenzyme Q reductase electron transport chain and, 796–797 structural characteristics of, 796–797 Succinic acid, derivatives, metabolic functions for, 482–483 Succinyl CoA amino acid degradation product, 890 citric acid cycle and, 791, 794 Sucrose consumption figures for, 588 hydrolysis of, 586–587 natural food sources and, 588–589 occurrence of, 586 structure of, 586 Sugar A general designation for either a monosaccharide or a disaccharide, 569 acidic, 578 amino, 581–582 artificial sweetners and, 590 blood, 572 brain, 573 fruit, 573 invert, 586 malt, 582 milk, 585–586 natural, 598 reducing, 578 refined, 598 sweetness scale for, 590 table, 586 Sugar alcohol, 579 Sulfa drugs, mode of action, 715–716 Sulfhydryl group The —SH functional group, 429 Sulfide, 431 Sulfoxides dimethylsulfoxide, 464 synthesis of, from sulfides, 464 Sulfuric acid acid rain, component of, 272 amino acid catabolism and, 888 esters of, 503

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Index/Glossary

eye irritation from, 449 properties of, 156 uses of, 156 Superimposable mirror image Mirror images that coincide at all points when the images are laid upon each other, 558 Superoxide ion, 805–806 Supersaturated solution An unstable solution that temporarily contains more dissolved solute than that present in a saturated solution, 194 characteristics of, 194 Suspension A heterogeneous mixture that contains dispersed particles that are heavy enough that they settle out under the influence of gravity, 209 characteristics of, 209 Symmetrical addition reaction An addition reaction in which identical atoms (or groups of atoms) are added to each carbon of a carbon–carbon multiple bond, 373 alkene halogenation, 375 alkene hydrogenation, 374–375 Synonyms, 753 Synthase, 790 Synthetic elements, 301 Tagamet, 265 Tartaric acid, 479–480 Taste chemical sense of, relationship to molecular geoemtry, 122 Taurocholic acid, 641 Teflon, 380 Temperature absolute zero, Charles’s law and, 171 enzyme activity and, 706 lowest possible value of, 42 normal, for human body, 44 optimum, for enzymes, 706 scales for measuring, 42 significant figures and measurement of, 43 solubility of solutes and, 193–194 vapor pressure magnitude and, 179 Temperature scales Celsius, characteristics of, 42–43 conversions between, 42–43 Fahrenheit, characteristics of, 42–43 Kelvin, characteristics of, 42–43 Terephthalic acid PET monomer, 499 Terpene An organic compound whose carbon skeleton is composed of two or more 5-carbon isoprene structural units, 371 alkene, 371–372 isoprene units and, 371–372 selected examples of, 372 Tertiary alcohol An alcohol in which the hydroxyl-bearing carbon atom is bonded to three other carbon atoms, 410 hydrogen bonding and, 410 structural characteristics of, 410 Tertiary amide An amide in which two alkyl (or aryl) groups and no hydrogen atoms are bonded to the amide nitrogen atom, 532

Tertiary amine An amine in which the nitrogen atom is bonded to three hydrocarbon groups and no hydrogen atoms, 515 Tertiary carbon atom A carbon atom in an organic molecule that is bonded to three other carbon atoms, 338 Tertiary protein structure The overall threedimensional shape of a protein that results from the interactions between amino acid side chains (R groups) that are widely separated from each other within the peptide chain, 674 insulin, 675 interactions responsible for, 674–677 myoglobin, 676 Testosterone, 642 Tetrahydrofuran, 428 Theobromine amount present in chocolate, 531 pharmacology of, 531 structure of, 531 Thermal expansion A measure of the change in volume of a sample of matter resulting from a temperature change, 163 states of matter and, 163–164 Thermogenin, 803 Thiamine coenzyme functions of, 722–724 dietary sources of, 725 structure of, 722–723 Thiocarbonyl group, 464 Thioester A sulfur-containing analog of an ester in which an —SR group has replaced the —OR group, 497 examples of, 497–498 Thioether An organic compound in which a sulfur atom is bonded to two carbon atoms by single bonds, 431 nomenclature of, 431 properties of, 431 Thiol An organic compound in which a —SH group is bonded to a saturated carbon atom, 429 functional group for, 429 generalized formula for, 429 nomenclature of, 429–430 oxidation of, 431 physical properties of, 430 Thromboxane A messenger lipid that is a C20fatty-acid derivative that contains a cyclic ether ring and oxygen-containing functional groups, 645 biochemical functions of, 645 structural characteristics of, 645 Thymine nucleotide subunit, 735, 737 structure of, 735, 737 Thymol, 422 Titration, acid–base, 282, 284–285 Tobacco, radioactivity associated with, 303 Tocopherols, 727 Tollens test aldehyde oxidation and, 455–456 monosaccharides and, 578 polysaccharides and, 590 reducing sugars and, 578

A-55

Toluene, 386 Tooth enamel demineralization and mineralization in, 100 fluoride ion and, 100 polyatomic ions and, 100 Torr, pressure unit of, 168 Torricelli, Evangelista, 168 Trace mineral importance of, human body and, 64 Trans- A prefix that means “across from,” 343 meaning of, 343 trans-enoyl CoA beta oxidation pathway and, 847–848 Trans fat, 626 Transamination reaction A biochemical reaction that involves the interchange of the amino group of an alpha-amino acid with the keto group of an alpha-keto acid, 879 examples of, 880 Transcription The process by which DNA directs the synthesis of mRNA molecules that carry the coded information needed for protein synthesis, 749 base-pairing associated with, 750 steps in, 750 Transcriptome All of the mRNA molecules that can be generated from the genetic material in a genome, 752 Transfer RNA (tRNA) RNA that delivers amino acids to the sites of protein synthesis, 749 activation of, protein synthesis and, 759 amino acids and, 757–758 anticodons and, 756–758 general shape of, 756–758 Transferase An enzyme that catalyzes the transfer of a functional group from one molecule to another, 701 examples of, 701–702 Transformation The process of incorporating recombinant DNA into a host cell, 767 recombinant DNA production and, 767–768 Transition element An element located in the d area of the periodic table, 75 electronic characteristics of, 75 need for, human body and, 74 periodic table location of, 75 Translation The process by which mRNA codons are deciphered and a particular protein is synthesized, 758 elongation step in, 759–761 general steps of, 758–762 initiation step in, 759 post-translation processing, aspects of, 762 summary-diagram for, 764 termination step in, 762 tRNA activation step in, 759 Translocation The part of translation in which a ribosome moves down an mRNA molecule three base positions (one codon) so that a new codon can occupy the ribosomal A site, 760 messenger RNA and, 759–761 ribsomes and, 759–761 Transmembrane protein, 683

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A-56

Index/Glossary

Transmutation reaction A nuclear reaction in which a nuclide of one element is changed into a nuclide of another element, 300 bombardment, nuclear equation for, 300 radioactive decay, nuclear equation for, 300 types of, 300 Transport protein, 683 Tretinoin, 481 Triacylglycerol A lipid formed by esterification of three fatty acids to a glycerol molecule, 615 chemical reactions of, 621–629 complete hydrolysis and, 622 dietary considerations and, 618–621 dietary lipid digestion product, 842–844 fatty acid composition of, 618 generalized structure for, 615 hydrogenation of, 625–626 hydrolysis of, 621–623 hydrolysis of, digestion and, 843–844 incomplete hydrolysis and, 622 mixed, 615–616 mobilization of, 845 occurrence of, 615 oxidation of, 627–629 saponification of, 623–625 simple, 615–616 storage of, adipose cells and, 845 storage of, energy reserves associated with, 845 structural characteristics of, 614–617 summary diagram, classification systems, 628 types of, 615–616 Triacylglycerol mobilization The hydrolysis of triacylglycerols stored in adipose tissue, followed by the release into the bloodstream of the fatty acids and glycerol so produced, 845 fatty acid oxidation and, 845 glycerol production and, 845 products of, 845 Triatomic molecule A molecule that contains three atoms, 13 examples of, 13–14 Tricarboxylic acid cycle. See citric acid cycle Triglyceride, 615 Triple covalent bond A covalent bond in which two atoms share three pairs of electrons, 112 molecules containing, examples of, 112 notation for, 112 relative strength of, 112 Triprotic acid An acid that supplies three protons (H⫹ ions) per molecule during an acid-base reaction, 257 examples of, 257 Tritium, hydrogen isotope, 55 tRNA. See Transfer RNA Turnover number The number of substrate molecules transformed per minute by one molecule of enzyme under optimum conditions of temperature, pH, and saturation, 708 Tylenol, 538 Tyndall, John, 208

Tyndall effect The light-scattering phenomenon that causes the path of a beam of visible light through a colloidal dispersion to be visible, 208 UDP-glucose, glycogenesis and, 828–829 Uncertainty determination of, scientific notation and, 34 determination of, decimal numbers, 30 origin of, measurements and, 26 Uncoupling agent, 803 Units conversion factors between, table of, 36 English and metric compared, 24 heat energy, 43 mathematical operations and, 36 metric, of length, 23–24 metric, of mass, 24–25 metric, of volume, 25 Universe, elemental composition of, 9–10 Unsaturated fatty acid b oxidation pathway and, 851 lipogenesis and, 863–864 mono-, 610–613 poly-, 610–613 Unsaturated hydrocarbon A hydrocarbon in which one or more carbon–carbon multiple bonds (double bonds, triple bonds, or both) are present, 323, 361 alkene, 361–382 alkyne, 382–384 aromatic hydrocarbon, 384–391 types of, 362 Unsaturated solution A solution that contains less than the maximum amount of solute that can be dissolved under the conditions at which the solution exists, 194 Unstable nuclide A nuclide with an unstable nucleus, a nucleus that spontaneously undergoes change, 293 factors affecting stability of, 293 Unsymmetrical addition reaction An addition reaction in which different atoms (or groups of atoms) are added to the carbon atoms of a carbon-carbon multiple bond, 373 alkene hydration, 376 alkene hydrohalogenation, 375–376 Uracil nucleotide subunit, 735, 737 structure of, 735, 737 Urea nitrogen atom sources for, urea cycle and, 885–886 physical properties of, 535, 884 production of, urea cycle and, 884–887 Urea cycle The series of biochemical reactions in which urea is produced from ammonium ions and carbon dioxide, 884 fuel for, carbamoyl phosphate, 884 linkage to citric acid cycle, 888 net chemical reaction for, 888 nitrogen content of compounds in, 887 steps in, 884–887 Urethane A hydrocarbon derivative that contains a carbonyl group bonded to both an —OR group and a —NHR (or —NR2) group, 544

preparation reaction for, 544 structural characteristics of, 544 Uric acid, formation of, 887 Urine, chemical composition of, 889 Urobilin, bile pigment, 894–895 Vaccine A preparation containing an inactive or weakened form of a virus or bacterium, 765 relationship to viruses, 765 Valence electron An electron in the outermost electron shell of a representative element or noble-gas element, 84 bonding, 110 determining number of, in atoms, 85–86 generalizations concerning, 86 Lewis symbols and, 84–86 nonbonding, 110 number of covalent bonds formed and, 112–113 octet rule and, 86–87 Vanillin, 422, 451 Vapor A gas that exists at a temperature and pressure at which it would ordinarily be thought of as a liquid or a solid, 177 Vapor pressure The pressure exerted by a vapor above a liquid when the liquid and vapor are in equilibrium with each other, 179 factors affecting magnitude of, 179 lowering of, solutes and, 209 table of, for water, 179 Vaseline, 348 Vasopressin, 667–668 Vioxx, 646 Virus A small particle that contains DNA or RNA (but not both) surrounded by a coat of protein and that cannot reproduce without the aide of a host cell, 763 mode of operation of, 763–765 nucleic acid content of, 763 vaccines and, 765 Vision, cis–trans isomers and, 371 Vitamin An organic compound, essential in small amounts for the proper functioning of the human body, that must be obtained from dietary sources because the body cannot synthesize it, 718 fat-soluble, 720, 725–729 general characteristics of, 718–720 solubility-polarity relationships for, 199 supplement, trace minerals and, 64 water-soluble, 720–725 Vitamin A b-carotene and, 726 biochemical functions of, 726 structural forms of, 725 Vitamin B coenzyme function of, 722–724 nomenclature for, 722 structural forms of, 722–723 Vitamin B12 coenzyme functions of, 724 dietary sources of, 725 structure of, 723 Vitamin B6 coenzyme functions of, 724

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Index/Glossary

dietary sources of, 725 structural forms of, 723 Vitamin C biochemical functions of, 721 dietary sources of, 721–722 structural forms of, 721 Vitamin D biochemical functions of, 727 structural forms of, 726–727 Vitamin E biochemical functions of, 728 structure of, 727–728 Vitamin K biochemical functions of, 728–729 structural forms of, 728 VLDL biochemial functions of, 690–691 structural characteristics of, 690–691 Volatile substance A substance that readily evaporates at room temperature because of a high vapor pressure, 179 Volume calculation of, using density, 41 conversion factors involving, 35–36 metric units of, 25 VSEPR electron group A collection of valence electrons present in a localized region about the central atom in a molecule, 119 characteristics of, 119 VSEPR theory A set of procedures for predicting the molecular geometry of a molecule using the information contained in the molecule’s Lewis structure, 118

angular arrangements in, 119 linear arrangements in, 119 steps involved in applying, 119 tetrahedral arrangements in, 120 trigonal planar arrangements in, 119–120 trigonal pyramidal arrangements in, 120 use of, in determining molecular shape, 118–121 Water density of, 184 electron transport chain production of, 798–799 free radical, 304 fresh, 90 hard, 90 ion-product constant for, 263–264 properties of, hydrogen bonding and, 183–184 sea, 90 self-ionization of, 263–264 soft, 90 Water free radical, 304 Wax A pliable, water-repelling substance used particularly in protecting surfaces and producing polished surfaces, 647 biological, 646–647 ear, 648 mineral, 648 paraffin, 648 Weak acid An acid that transfers only a small percentage of its protons (H⫹ ions) to water when in an aqueous solution, 259 extent of proton transfer for, 259–260

A-57

Weak base, ammonia as a, 259 Weak electrolyte A substance that incompletely ionizes/dissociates into ions in aqueous solution., 279 characteristics of, 279–280 Weight A measure of the force exerted on an object by gravitational forces, 24 distinction between mass and, 24–25 Wood alcohol, 404 Wool, 543 Xanthine, 526 Xylenes, 388 Xylocaine, 536 Zaitsev, Alexander, 412 Zaitsev’s rule The major product in an intramolecular alcohol dehydration reaction is the alkene that has the greatest number of alkyl groups attached to the carbon atoms of the double bond, 412 use of, 412–415 Zantac, 265 Zocor, 867 Zwitterion A molecule that has a positive charge on one atom and a negative charge on another atom but that has no net charge, 660 guidelines for determining structural form of, 660–661 structure change with pH, 660–661 Zymogen The inactive precursor of a proteolytic enzyme, 714