Biochemistry [2 ed.] 9780367461874, 0367461870, 9780367465537, 0367465531

Table of contents :
Cover
Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Preface to the First Edition
Preface to the Second Edition
Acknowledgments
Author
Glossary
Chapter 1 Foundations
1.1 Origins of Biochemistry
1.2 Some Chemical Ideas
1.2.1 Reactions and Their Kinetic Description
1.2.1.1 Equilibrium
1.2.2 The Steady-State
1.3 Acid–Base Reactions
1.4 Redox
1.5 Energy
1.6 Cell Theory
1.7 Species Hierarchy and Evolution
1.8 Biological Systems
Key Terms
Bibliography
Chapter 2 Water
2.1 Structure of Water
2.1.1 Gas Phase Water
2.1.2 Partial Charges and Electronegativity
2.1.3 Condensed Phase Water: Hydrogen Bonding
2.1.4 Hydrogen Bonding in Condensed Phase Water
2.2 The Hydrophobic Effect
2.3 Molecules Soluble in Water
2.4 High Heat Retention: The Unusual Specific Heat of Liquid Water
2.5 Ionization of Water
2.6 Some Definitions for the Study of Acids and Bases
2.7 The pH Scale
2.8 The Henderson–Hasselbalch Equation
2.9 Titration and Buffering
Summary
Review Questions
Chapter 2 Addendum: The Dielectric
Key Terms
Bibliography
Chapter 3 Lipids
3.1 Significance
3.2 Fatty Acids
3.3 Triacylglycerols
3.4 Phospholipids
3.5 Cholesterol
3.6 Lipid–Water Interactions of Amphipathic Molecules
3.7 Phospholipid Monolayers
3.8 Lipid Composition of Membranes
3.9 Water Permeability of Membranes and Osmosis
Summary
Review Questions
Chapter 3 Addendum: Inverted Micelles
Key Terms
Bibliography
Chapter 4 Carbohydrates
4.1 Monosaccharides
4.2 Ring Formation in Sugars
4.3 Disaccharides
4.4 Polysaccharides
4.4.1 Linear Polysaccharides
4.4.2 Branched Polysaccharides
4.5 Carbohydrate Derivatives
4.5.1 Simple Modifications
4.5.2 Substituted Carbohydrates
Summary
Review Questions
Chapter 4 Addendum: The Discovery of Stereoisomerism
Key Terms
Bibliography
Chapter 5 Amino Acids and Proteins
5.1 Common Structure of the Amino Acids
5.2 Biology of the Amino Acids
5.3 Amino Acid Individuality: The R Groups
5.3.1 Polarities
5.3.2 Functional Groups
5.4 Acid–Base Properties and Charge
5.4.1 Titration and Net Charge
5.4.2 Interactions between the α-Carboxylate and α-Amine Groups
5.4.2.1 Inductive Effect
5.4.2.2 Electric Field Effect
5.4.3 Multiple Dissociable Groups
5.5 The Peptide Bond
5.6 Peptides and Proteins
5.7 Levels of Protein Structure
5.7.1 Primary Structure
5.7.2 Secondary Structure
5.7.2.1 α-Helix
5.7.2.2 β-Sheet
5.7.3 Domains
5.7.4 Tertiary Structure
5.7.5 Quaternary Structure
5.8 Protein Folding
5.9 Oxygen Binding in Myoglobin and Hemoglobin
5.10 Other Binding Reactions Involving Proteins
5.10.1 Extracellular Binding Proteins
5.10.2 Cell Surface Binding Proteins
5.10.3 Intracellular Binding Proteins
5.11 Protein Purification and Analysis
5.11.1 Purification
5.11.2 Analysis
Summary
Review Questions
Chapter 5 Addendum: Atomic Charged Forms
Key Terms
Bibliography
Chapter 6 Enzymes
6.1 Energetics of Enzyme-Catalyzed Reactions
6.2 The Enzyme Assay and Initial Velocity
6.3 A Simple Kinetic Mechanism
6.3.1 Assumptions
6.3.2 The Michaelis–Menten Equation
6.4 How the Michaelis–Menten Equation Describes Enzyme Behavior
6.5 The Meaning of Km
6.6 Reversible Inhibition
6.6.1 Competitive Inhibition
6.6.2 Anticompetitive Inhibition (Uncompetitive)
6.6.3 Mixed Inhibition (Noncompetitive)
6.7 Double-Reciprocal or Lineweaver–Burk Plot
6.8 Allosteric Enzymes
6.9 Irreversible Inhibition
6.10 Enzyme Mechanisms
6.10.1 Nucleophilic Substitution
6.10.2 Acid–Base Catalysis
6.11 Enzyme Categories
6.12 Enzyme-Like Qualities of Membrane Transport Proteins
Summary
Review Questions
Chapter 6 Addendum: The Haldane Relationship
Key Terms
Bibliography
Chapter 7 Coenzymes
7.1 Coenzymes: Bound and Mobile
7.2 Coenzymes and Vitamins
7.3 Redox Coenzymes
7.3.1 Nicotinamides
7.3.2 Ubiquinone
7.3.3 Flavin Coenzymes
7.4 Acyl Transfers
7.4.1 CoA
7.4.2 Carnitine
7.4.3 Lipoic Acid
7.5 Carboxylation
7.5.1 Biotin
7.5.2 Vitamin K
7.6 Exchange Coenzymes
7.6.1 Thiamine Pyrophosphate
7.6.2 Pyridoxal Phosphate
7.7 Metal Ion Cofactors
7.7.1 Mg2+
7.7.2 Iron
7.7.3 Copper
7.7.4 Co2+
7.7.5 Mn2+and Zn2+
7.7.6 Selenium
7.7.7 Dietary Essentials
Review Questions
Chapter 7 Addendum: The Vitamin K Cycle
Key Terms
Bibliography
Chapter 8 Metabolism and Energy
8.1 Origins of Thermodynamics
8.2 First Law of Thermodynamics
8.2.1 Heat and Work
8.2.2 Enthalpy
8.3 Entropy and the Second Law of Thermodynamics
8.3.1 Entropy as a Ratio of Heat to Temperature
8.3.2 Entropy as a Statistical Distribution of States
8.4 Free Energy
8.5 Standard Free Energy
8.6 Nonstandard Free Energy Changes
8.7 Near-Equilibrium and Metabolically Irreversible Reactions
8.8 ATP
8.9 Energy Coupling with ATP
8.9.1 Creatine Phosphokinase
8.9.2 NDP Kinase
8.9.3 Adenylate Kinase
8.10 Energy of Redox Reactions
8.10.1 Electricity Fundamentals
8.10.2 The Electrochemical Cell
8.10.3 Standard Reduction Potentials
8.10.4 Reduction Potentials and Free Energy
8.10.5 Reduction Potentials
8.11 Mobile Cofactors and the Pathway View
Summary
Review Questions
Chapter 8 Addendum: Free Energy Derivation
Key Terms
Bibliography
Chapter 9 Glycolysis
9.1 Glucose Transport
9.2 From Glucose to Pyruvate
9.2.1 Hexokinase
9.2.2 Glucose Phosphate Isomerase
9.2.3 Phosphofructokinase
9.2.4 Aldolase
9.2.5 Triose Phosphate Isomerase
9.2.6 Glyceraldehyde Phosphate Dehydrogenase
9.2.7 Phosphoglycerate Kinase
9.2.8 Phosphoglycerate Mutase
9.2.9 Enolase
9.2.10 Pyruvate Kinase
9.3 Completing the Pathway
9.3.1 Lactate Formation
9.3.2 Ethanol Formation
9.4 Energetics of Glycolysis
9.4.1 Pathway Thermodynamics
9.4.2 Red Blood Cell Shunt Pathway
9.4.3 Arsenate Poisoning
9.4.4 Fructose Metabolism
9.4.5 Energy Balance and Glycolytic Connections
9.5 Metabolic Connections to Glycolysis
9.5.1 Alternative Entry Points
9.5.2 Glycolytic Intermediates as Intersection Points
9.5.3 Alternative Endpoints of Glycolysis
Summary
Review Questions
Chapter 9 Addendum: Alternatives to Glycolysis
Key Terms
Bibliography
Chapter 10 The Krebs Cycle
10.1 A Cyclic Pathway
10.2 Acetyl-CoA: Substrate of the Krebs Cycle
10.3 Overview of Carbon Flow
10.4 Steps of the Pathway
10.4.1 Citrate Synthase
10.4.2 Aconitase
10.4.3 Cis-Aconitate as a Krebs Cycle Intermediate
10.4.4 Prochirality
10.4.5 The R/S System of Nomenclature
10.4.6 Fluoroacetate Poisoning
10.4.7 Isocitrate DH
10.4.8 α-Ketoglutarate DH Complex
10.4.9 Succinyl-CoA Synthetase
10.4.10 Succinate DH
10.4.11 Fumarase
10.4.12 Malate DH
10.5 Energy Balance
10.6 Regulation
10.7 Krebs Cycle as a Second Crossroad of Metabolic Pathways
Summary
Review Questions
Chapter 10 Addendum: Cyclic Pathways Connected to the Krebs Cycle
1. Glyoxylate Cycle
2. Itaconate Pathway
Key Terms
Bibliography
Chapter 11 Oxidative Phosphorylation
11.1 The Phenomenon
11.2 Mitochondrial Inner Membrane
11.3 Carriers of Electrons, Protons, or Both
11.3.1 Carriers of Electrons
11.3.2 Carriers of Protons
11.3.3 Carriers of Both Electrons and Protons
11.4 Membrane-Bound Complexes
11.5 The Electrochemical Cell and the Mitochondria
11.6 Electron Pathways
11.6.1 Sequence of Electron Flow
11.6.2 Energetics of Electron Flow
11.7 Mechanisms of the Mitochondrial Membrane Protein Complexes
11.7.1 Complex I: Proton Pump
11.7.2 Complex II: Succinate Dehydrogenase
11.7.3 Complex III: Loop Mechanism
11.7.4 Complex IV: Pump and Annihilation
11.7.5 Complex V: ATP Synthesis
11.7.5.1 The Stator
11.7.5.2 The Rotor
11.8 Proton-Motive Force
11.8.1 Electric Circuit Analogy to the Proton Gradient
11.8.2 Utilization of Δp beyond ATP Synthesis
11.9 Mitochondrial Membrane Transport
11.9.1 Adenine Nucleotide Translocase
11.9.2 Phosphate Exchange
11.9.3 Other Transport Proteins
11.9.4 Coupling of Oxidation and Phosphorylation
11.10 Uncoupling
11.10.1 Physiological Uncoupling: Brown Fat
11.11 Superoxide Formation by Mitochondria
11.12 Control of Mitochondria
11.13 How Mitochondria Can Utilize Cytosolic NADH
11.13.1 Glycerol Phosphate Shuttle
11.13.2 Malate/Aspartate Shuttle
Summary
Review Questions
Chapter 11 Addendum: Supercomplexes
Key Terms
Bibliography
Chapter 12 Photosynthesis
12.1 Light and Carbon Reactions
12.2 Chloroplasts
12.2.1 Orientations: N and P Sides of the Membrane
12.2.2 Light Reactions of Photosynthesis as a Reversed Oxidative Phosphorylation
12.2.3 Carbon Reactions of Photosynthesis: CO2 Fixation
12.3 Harnessing Light Energy
12.3.1 Light Absorption and the Antennae
12.3.2 Electron Transfer at Reaction Centers
12.4 Proton and Electron Flow for the Light Reactions
12.5 Cyclic Electron Transfer and Other Variations
12.6 The Calvin Cycle
12.6.1 Ribulose Bisphosphate Carboxylase
12.6.2 Reaction Steps Following Carbon Fixation to Glyceraldehyde-P: Energy Consuming Portion
12.6.3 From GAP to the RuBP: Overview
12.6.4 From GAP to the RuBisCo Step: Reactions
12.7 Variations in CO2 Handling: C3, C4, and CAM Plants
12.8 Pathway Endpoints: Sucrose and Starch
Summary
Review Questions
Chapter 12 Addendum: Dark vs Carbon Reactions
Key Terms
Bibliography
Chapter 13 Carbohydrate Pathways Related to Glycolysis
13.1 Glycogen Metabolism
13.1.1 Glycogen Synthesis
13.1.2 Glycogenolysis
13.1.3 Physiological Context of Glycogen Metabolism
13.1.4 Regulation of Glycogen Metabolism by Glucagon
13.1.5 Regulation of Glycogen Metabolism by Epinephrine
13.1.6 Regulation of Glycogen Metabolism by Insulin
13.1.7 Regulation of Glycogen Metabolism by AMP Kinase
13.2 Gluconeogenesis
13.2.1 Lactate Dehydrogenase as a Gluconeogenic Enzyme
13.2.2 Pyruvate to PEP
13.2.3 Indirect Transport of Oxaloacetate from Mitochondria to Cytosol
13.2.4 Fructose-1,6-P2 to Fructose-6-P
13.2.5 Glucose-6-P to Glucose
13.2.6 Pathway Integration: Glycolysis, Glycogen Metabolism, and Gluconeogenesis
13.2.6.1 The Feeding–Fasting Transition
13.2.6.2 The Resting–Exercise Transition
13.3 The Pentose Phosphate Shunt
13.3.1 Oxidative Stage
13.3.2 Nonoxidative Stage
13.3.2.1 Reactions of the Nonoxidative Stage
13.3.2.2 A Pseudo Three-Dimensional View and Comparison to the Calvin Cycle
13.3.3 Distribution Between NADPH Production and Ribose-5-P
13.4 Galactose Utilization
Summary
Review Questions
Chapter 13 Addendum: Phosphorylation of Glycogen
Key Terms
Bibliography
Chapter 14 Lipid Metabolism
14.1 Absorption of Dietary Lipids
14.2 Fatty Acid Oxidation
14.2.1 Activation
14.2.2 Transport
14.2.3 β-Oxidation
14.2.3.1 Unsaturated Fatty Acids
14.2.3.2 Odd Carbon-Numbered Fatty Acids
14.2.3.3 Shorter and Longer Fatty Acids
14.3 Ketone Body Metabolism
14.4 Fatty Acid Biosynthesis
14.4.1 Export of Acetyl-CoA to the Cytosol
14.4.2 Carboxylation of Acetyl-CoA to Malonyl-CoA
14.4.3 Sequential Addition of Two-Carbon Fragments to Form Palmitate
14.4.3.1 Loading
14.4.3.2 Condensation
14.4.3.3 Reduction
14.4.3.4 Dehydration
14.4.3.5 Second Reduction
14.5 Triacylglycerol Formation
14.6 Phospholipid Metabolism
14.7 Cholesterol Metabolism
14.8 Other Lipids
14.8.1 Eicosanoids
14.8.2 Sphingolipids
14.8.3 Unusual Bacterial Fatty Acids
14.9 Overview of Lipid Metabolism in the Fed and Fasted States
14.10 Integration of Lipid and Carbohydrate Metabolism
14.10.1 Lipid and Carbohydrate Intersections in the Feeding–Fasting Transition
14.10.2 Lipid and Carbohydrate Intersections in the Resting–Exercise Transition
14.10.3 Lipid and Carbohydrate Intersections in Diabetes Mellitus
Summary
Review Questions
Chapter 14 Addendum: The Isoprenes
Key Terms
Bibliography
Chapter 15 Nitrogen Metabolism
15.1 The Nitrogen Cycle
15.2 Reaction Types in NH3 Assimilation
15.2.1 Redox-Neutral
15.2.2 Redox-Active
15.2.3 Redox-Balanced
15.3 Metabolically Irreversible Nitrogen Exchange Reactions
15.4 Near-Equilibrium Nitrogen Exchange Reactions
15.4.1 Glutamate DH
15.4.2 Transaminases
15.5 The Urea Cycle
15.5.1 [NH3] Exceeds [Aspartate]
15.5.2 [Aspartate] Exceeds [NH3]
15.5.3 Steps from NH3 to Citrulline
15.5.4 Cytosolic Steps of the Urea Cycle
15.5.5 Overall Urea Cycle
15.6 Amino Acid Metabolism: Catabolism
15.6.1 Branched-Chain Amino Acid Breakdown
15.6.2 Threonine
15.6.3 Lysine
15.6.4 Tryptophan
15.6.5 Phenylalanine and Tyrosine Degradation
15.6.6 Amino Acids Directly Connected to Major Metabolic Pathways
15.6.7 Arginine, Proline, and Histidine Are All Converted to Glutamate
15.6.8 One-Carbon (1C) Metabolism and Serine, Glycine, and Methionine Breakdown
15.7 Amino Acids: Anabolism
15.7.1 Nonessential Amino Acids
15.7.2 Essential Amino Acids
15.7.3 Aromatic Amino Acid Biosynthesis
15.8 Nucleotide Metabolism
15.8.1 Pyrimidine Synthesis
15.8.2 Pyrimidine Degradation
15.8.3 Purine Synthesis
15.8.4 Purine Degradation
15.8.5 Salvage Reactions
15.8.6 Purine Nucleotide Regulation
15.8.7 Purine Nucleotide Cycle
15.8.8 Deoxynucleotide Formation
15.8.9 A Unique Methylation to Form dTMP
15.9 Other Nitrogen Pathways
Summary
Review Questions
Chapter 15 Addendum: Nitrogen Disposal
The Tilapia of Lake Magadi
The Alligator and the Crocodile
Low Creatinine and Liver Failure
Key Terms
References
Chapter 16 Nucleic Acids
16.1 Strand Structures of the Nucleic Acids
16.2 Structure of the Double Helix
16.3 Supercoiling
16.4 Histones
16.5 Replication
16.5.1 Initiation
16.5.2 Replication Fork and the Replisome
16.5.3 Primer Formation
16.5.4 Creating the Double Helix
16.5.5 Distinctive Features of Eukaryotic Replication
16.6 DNA Repair
16.6.1 Mismatch Repair
16.6.2 Excision Repair
16.6.3 PARP
16.7 Transcription
16.7.1 RNA Polymerase Binding to DNA
16.7.2 Transcription Events in E. coli
16.7.3 Eukaryotic Transcription
Summary
Review Questions
Chapter 16 Addendum: Restriction Enzymes and PCR
Restriction Enzymes
PCR
Key Terms
Bibliography
Chapter 17 Protein Synthesis and Degradation
17.1 Three Forms of RNA Employed in Protein Synthesis
17.1.1 tRNA
17.1.2 rRNA and the Ribosomes
17.2 The Genetic Code
17.3 Steps in Protein Synthesis
17.3.1 Initiation
17.3.2 Elongation
17.3.3 Termination
17.3.4 Distinctive Features of Eukaryotic Translation
17.3.5 Regulation of Eukaryotic Translation
17.4 Co-Translational and Post-Translational Modifications of Proteins
17.4.1 Co-Translational Modifications
17.4.2 Post-Translational Modifications
17.5 Protein Degradation
17.5.1 Extracellular Proteases
17.5.2 Intracellular Proteases
17.6 The mTOR Pathway in the Control of Protein Synthesis
Summary
Review Questions
Chapter 17 Addendum: Skeletal Muscle and Exercise
Key Terms
Bibliography
Appendix
Index