Marks' Basic Medical Biochemistry: A Clinical Approach [5 ed.] 1496324811, 2017016094, 9781496324818, 9781496387721, 1496387724

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MICHAEL LIEBERMAN ALISA FEET

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MARKS'

BASIC MEDICAL BIOCHEMISTRY

A Clinical Approach _

5TH EDITION

MARKS'

BASIC MEDICAL BIOCHEMISTRY

A Clinical Approach

5TH EDITION

Michael Lieberman, PhD Disti ngu ished Teach i ng Professor Department of Molecu lar Genetics, Biochemistry and M i crobiology U n iversity of Cincin nati Co l l ege of Medicine Cincinnati, Ohio

Alisa Peet, MD Associate Dean C l i n ical Education Associate Professor of C l i n ical Medicine Lewis Katz School of Medicine at Temple U n iversity Phi ladelph ia, Pen n sylvan ia

Illustrations by Matthew Chansky

$Wolters Kluwer Philadelphia · Baltimore • New York · London Buenos Aires · Hong Kong · Sydney · Tokyo

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Copyright© 2018 Wolters Kluwer Copyright© 2013, 2009 by Lippincott Williams

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Wilkins, a Wolters Kluwer business. All rights reserved. This book is protected by copyright. No part of this book

may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. To request permission, please contact Wolters Kluwer at Two Commerce Square, 200 via our website at lww.com (products and services). 9

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Library of Congress Cataloging-in-Publication Data

Names: Lieberman, Michael, 19 50 - author. I Peet, Alisa, author. Title: Marks' basic medical biochemistry : a clinical approach Lieberman, Alisa Peet; illustrations by Matthew Chansky. Other titles: Basic medical biochemistry Description: Fifth edition.

I

I Michael

Philadelphia : Wolters Kluwer, [2018]1

Includes bibliographical references and index. Identifiers: LCCN 2017016094

I

ISBN 9781496324818

Subjects: I MESH: Biochemical Phenomena

I

Clinical Medicine

Classification: LCC QP514.21 NLM QU 341 DDC 61 2 .1 /lll-dc23 LC record available at

https://1ccn.loc.gov/2017016094

This work is provided "as is," and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based upon healthcare professionals' examination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data, and other factors unique to the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Healthcare professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, ap­ propriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer's package insert) accompanying each drug to verify, among other things, conditions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medi­ cation to be administered is new, infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the publisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. LW W.com

Preface to the 5th Edition

It has been 5 years since the fourth edition was completed. The fifth edition has some significant organizational changes, as suggested by extensive surveys of fac­ ulty and students who used the fourth edition in their classes and studies . The maj or pedagogic features of the text remain. They have been enhanced by the following changes for the fifth edition: 1 . Every patient history has been reviewed and revised to reflect current standards of care (as of 20 1 6). The patient names have also been changed to a first name and last initial. A key indicating the "old" names and "new" names is available in the online supplement associated with the text. 2. The Biochemical Comments associated with each chapter have been updated, where appropriate, to allow students to experience where current research efforts are headed. 3. The presentation of metabolism has been altered such that glycolysis is now the first topic discussed, followed by the tricarboxylic acid cycle, and then oxidative phosphorylation. The correlation between fourth edition chapters and fifth edition chapters are as follows: a. Chapters 1 through 1 8, no change b. Section IV is now entitled "Carbohydrate Metabolism, Fuel Oxida­ tion, and the Generation of Adenosine Triphosphate" and consists of Chapters 1 9 through 28. i. Chapter 1 9 of the fifth edition (B asic Concepts in the Regulation of Fuel Metabolism by Insulin, Glucagon, and Other Hormones) is based on Chapter 26 of the fourth edition. 11. Chapter 20 of the fifth edition (Cellular Bioenergetics: Adenosine Triphosphate and 0 2 ) is based on Chapter 19 of the fourth edition. iii. Chapter 21 of the fifth edition (Digestion, Absorption, and Trans­ port of Carbohydrates) is based on Chapter 27 of the fourth edition. iv. Chapter 22 of the fifth edition (Generation of Adenosine Triphos­ phate from Glucose, Fructose, and Galactose: Glycolysis) is based on Chapter 22 of the fourth edition and also contains parts of Chapter 29 of the fourth edition (Pathways of Sugar Metabolism: Pentose Phosphate Pathway, Fructose, and Galactose Metabolism). v. Chapter 23 of the fifth edition (Tricarboxylic Acid Cycle) is based on Chapter 20 of the fourth edition. vi. Chapter 24 of the fifth edition (Oxidative Phosphorylation and Mi­ tochondrial Function) is based on Chapter 21 of the fourth edition. vii. Chapter 25 of the fifth edition (Oxygen Toxicity and Free-Radical Injury) is based on Chapter 24 of the fourth edition. viii. Chapter 26 of the fifth edition (Formation and Degradation of Glycogen) is based on Chapter 28 of the fourth edition. IX. Chapter 27 of the fifth edition (Pentose Phosphate Pathway and the Synthesis of Glycosides, Lactose, Glycoproteins, and Glyco­ lipids) is based on Chapter 30 of the fourth edition, along with a section (The Pentose Phosphate Pathway) of Chapter 29 of the fourth edition. This led to the deletion of old Chapter 29 from the Table of Contents of the fifth edition. v

vi

Preface to the 5th Edition

x. Chapter 28 of the fifth edition (Gluconeogenesis and Mainte­ nance of Blood Glucose Levels) is based on Chapter 3 1 of the fourth edition. c . Section V (Lipid Metabolism) now consists of the following chapters : 1. Chapter 29 of the fifth edition (Digestion and Transport of Dietary Lipids) is based on Chapter 32 of the fourth edition. ii. Chapter 30 of the fifth edition (Oxidation of Fatty Acids and Ketone Bodies) is based on Chapter 23 of the fourth edition. iii. Chapter 3 1 of the fifth edition (Synthesis of Fatty Acids, Triacylg­ lycerols, and the Maj or Membrane Lipids) is based on Chapter 33 of the fourth edition and also contains basic information concern­ ing the eicosanoids from Chapter 35 of the fourth edition. Material from Chapter 35 of the fourth edition that was not incorporated into Chapter 3 1 of the fifth edition is available as an online supple­ ment. A separate chapter on eicosanoid metabolism is not present in the fifth edition. iv. Chapter 32 of the fifth edition (Cholesterol Absorption, Synthesis, Metabolism, and Fate) is based on Chapter 34 of the fourth edition. v. Chapter 33 of the fifth edition (Metabolism of Ethanol) is based on Chapter 25 of the fourth edition. vi. Chapter 34 of the fifth edition (Integration of Carbohydrate and Lipid Metabolism) is based on Chapter 36 of the fourth edition. d. Section VI (Nitrogen Metabolism) has the same chapter order as in the fourth edition, but because two chapters have been deleted previously from the text, the chapter numbers in the fifth edition are two less than in the fourth edition. Section VI in the fifth edition comprises Chapters 35 through 40, whereas in the fourth edition, it is Chapters 37 through 42. e. Section VII (Tissue Metabolism) has the same chapter order as in the fourth edition, but the chapter numbers in the fifth edition are two less than in the fourth edition. Section VII in the fifth edition comprises Chapters 4 1 through 47, whereas in the fourth edition, it i s Chapters 4 3 through 49. 4. The number of printed review questions at the end of each chapter has been increased to 1 0, up from 5 questions per chapter in the fourth edition (470 total questions). The online question bank associated with the text has also been increased to 560 questions, as compared to 468 questions asso­ ciated with the fourth edition. Where possible, questions are presented in National Board of Medical Examiners format. As stated in previous editions, in revising a text geared primarily toward medi­ cal students, the authors always struggle with new advances in biochemistry and whether such advances should be included in the text. We have taken the approach of only including advances that will enable the student to better relate biochemistry to medicine and future diagnostic tools. Although providing incomplete, but exciting, advances to graduate students is best for their education, medical students benefit more from a more directed approach-one that emphasizes how biochemistry is useful for the practice of medicine. This is a maj or goal of this text. Any errors are the responsibility of the authors, and we would appreciate being notified when such errors are found. The accompanying website for this edition of Marks' Basic Medical Biochem­ istry: A Clinical Approach contains the aforementioned additional multiple-choice questions for review, a table listing patient names for the fifth edition and how they correspond to those of the fourth edition, summaries of all patients described in the text (patient cases), all chapter references and additional reading (with links to the article in PubMed, where applicable), a listing of diseases discussed in the book (with links to appropriate websites for more information), and a summary of all of the methods described throughout the text.

How to Use This Book

Icons identify the various components of the book: the patients who are presented at the start of each chapter; the clinical notes, methods notes, questions, and answers that appear in the margins; and the Key Concepts, Clinical Comments, and Bio­ chemical Comments that are found at the end of each chapter. Each chapter starts with an abstract that summarizes the information so that students can recognize the key words and concepts they are expected to learn. The next component of each chapter is The Waiting Room, describing patients with com­ plaints and detailing the events that led them to seek medical help. indicates a female patient indicates a male patient indicates a patient who is an infant or young child As each chapter unfolds, icons appear in the margin, identifying information related to the material presented in the text: indicates a clinical note, usually related to the patients in The Waiting Room for that chapter. These notes explain signs or symptoms of a patient or give some other clinical information relevant to the text. indicates a methods note, which elaborates on how biochemistry is required to perform, and interpret, common laboratory tests. Questions and answers also appear in the margin and should help to keep stu­ dents thinking as they read the text:

(!)

indicates a question indicates the answer to the question. The answer to a question is always located on the next page. If two questions appear on one page, the answers are given in order on the next page.

Each chapter ends with these three sections : Key Concepts, Clinical Comments, and Biochemical Comments : The Key Concepts summarize the important take-home messages from the chapter. The Clinical Comments give additional clinical information, often describing the treatment plan and the outcome. The Biochemical Comments add biochemical information that is not covered in the text or explore some facet of biochemistry in more detail or from another angle. Finally, Review Questions are presented. These questions are written in a United States Medical Licensing Examination-like format, and many of them have a clinical slant. Answers to the review questions, along with detailed explanations, are provided at the end of every chapter. vii

Acknowledgments The authors would like to thank Professor Kent Littleton of B astyr University, for his careful reading of the fourth edition and pointing out mistakes and errors that required correcting for the fifth edition. We greatly appreciate his efforts in im­ proving the text. Dr. Bonnie Brehm was instrumental in helping with the nutrition aspects of the text, and Dr. Rick Ricer was invaluable in writing questions, both for the text and the online supplement. We would also like to acknowledge the initial contributions of Dawn Marks, whose vision of a textbook geared toward medical students led to the first edition of this book. Her vision is still applicable today.

ix

Contents SECTION I Fuel Metabolism

1

Metabolic Fuels and Dietary Components

2

T he Fed or Absorptive State

3

Fasting

SECTION II

34

24

3

45

Chemical and Biologic Foundations of Biochemistr y

4

Water, Acids, Bases, and Buffers

5

Structures of the Major Compounds of the Body

6

Amino Acids in Proteins

7

Structure-Function Relationships in Proteins

8

Enzymes as Catalysts

9

Regulation of Enzymes

47

80

I 28

62

I 00

150

10

Relationship between Cell Biology and Biochemistry

11

Cell Signaling by Chemical Messengers

SECTION III

190

Gene Expression and the Synthesis of Proteins

12

Structure of the Nucleic Acids

13

Synthesis of DNA

14

Transcription: Synthesis of RNA

15

Translation: Synthesis of Proteins

16

Regulation of Gene Expression

17

Use of Recombinant DNA Techniques in Medicine

18

T he Molecular Biology of Cancer

230

SECTION IV

169

21 I

213 251

274

294

344

319

Carbohydrate Metabolism, Fuel Oxidation, and the Generation of Adenosine Triphosphate

19

Basic Concepts in the Regulation of Fuel Metabolism by Insulin, Glucagon, and Other Hormones

20 21

369

376

Cellular Bioenergetics: Adenosine Triphosphate and 02

Digestion, Absorption, and Transport of Carbohydrates

394

415

xi

xii

Contents

22

Generation of Adenosine Triphosphate from Glucose, Fructose, and Galactose: Glycolysis

434

23

Tricarboxylic Acid Cycle

24

Oxidative Phosphorylation and Mitochondrial Function

25

Oxygen Toxicity and Free-Radical Injury

26

Formation and Degradation of Glycogen

27

457

504

525

Pentose Phosphate Pathway and the Synthesis of Glycosides, Lactose, Glycoproteins, and Glycolipids

28

480

543

Gluconeogenesis and Maintenance of Blood Glucose Levels

SECTION V Lipid Metabolism

5 91

29

Digestion and Transport of Dietary Lipids

30

Oxidation of Fatty Acids and Ketone Bodies

31

Synthesis of Fatty Acids,Triacylglycerols, and the Major Membrane Lipids

594

607

631

32

Cholesterol Absorption, Synthesis, Metabolism, and Fate

33

Metabolism of Ethanol

34

Integration of Carbohydrate and Lipid Metabolism

SECTION VI Nitrogen Metabolism

702

735

666

719

35

Protein Digestion and Amino Acid Absorption

36

Fate of Amino Acid Nitrogen: Urea Cycle

37

Synthesis and Degradation of Amino Acids

38

Tetrahydrofolate,Vitamin B12, and S-Adenosylmethionine

39

Purine and Pyrimidine Metabolism

40

lntertissue Relationships in the Metabolism of Amino Acids

SECTION VII T issue Metabolism

75 I

738

769

806

41

Actions of Hormones that Regulate Fuel Metabolism

42

T he Biochemistry of Erythrocytes and Other Blood Cells

43

Blood Plasma Proteins, Coagulation, and Fibrinolysis

44

Liver Metabolism

45

Metabolism of Muscle at Rest and during Exercise

46

Metabolism of the Nervous System

47

T he Extracellular Matrix and Connective T issue

Patient Index Subject Index

997

I 000

790

843

91 0

953

566

845

893 932

978

823

869

Fuel Metabolism

I

n order to survive, humans must meet two basic metabolic requirements : We must be able to synthesize everything our cells need that is not supplied by our diet, and we must be able to protect our internal environment from toxins and changing conditions in our external environment. To meet these requirements, we metabolize our dietary components through four basic types of pathways: fuel oxidative pathways, fuel storage and mobilization pathways, biosynthetic path­ ways, and detoxification or waste disposal pathways. Cooperation between tissues and responses to changes in our external environment are communicated through transport pathways and intercellular signaling pathways (Fig. 1. 1 ) . The foods i n our diet are the fuels that supply u s with energy i n the form of calories . This energy is used for carrying out such diverse functions as moving, thinking, and reproducing. Thus, several of our metabolic pathways are fuel oxidative pathways that convert fuels into energy that can be used for biosynthetic and mechanical work. But what is the source of energy when we are not eating, such as between meals, and while we sleep? How does a person on a hunger strike that you read about in the morning headlines survive so long? We have other metabolic pathways that are fuel storage pathways. The fuels that we store can be mobilized during periods when we are not eating or when we need increased energy for exercise. Our diet also must contain the compounds we cannot synthesize, as well as all the basic building blocks for compounds we do synthesize in our biosynthetic pathways. For example, we have dietary requirements for some amino acids, but we can synthesize other amino acids from our fuels and a dietary nitrogen precur­ sor. The compounds required in our diet for biosynthetic pathways include certain amino acids, vitamins, and essential fatty acids . Detoxification pathways and waste disposal pathways are metabolic pathways devoted to removing toxins that can be present in our diets or in the air we breathe, introduced into our bodies as drugs, or generated internally from the metabolism of dietary components . Dietary components that have no value to the body, and must be disposed of, are called xenobiotics. In general, biosynthetic pathways (including fuel storage) are referred to as anabolic pathways; that is, pathways that synthesize larger molecules from smaller components . The synthesis of proteins from amino acids is an example of an anabolic pathway. Catabolic pathways are those pathways that break down larger molecules into smaller components . Fuel oxidative pathways are examples of catabolic pathways. In humans, the need for different cells to carry out different functions has resulted in cell and tissue specialization in metabolism. For example, our adipose tissue is a specialized site for the storage of fat and contains the metabolic path­ ways that allow it to carry out this function. However, adipose tissue is lacking many of the pathways that synthesize required compounds from dietary precursors . To enable our cells to cooperate in meeting our metabolic needs during changing conditions of diet, sleep, activity, and health, we need transport pathways into the blood and between tissues and intercellular signaling pathways. One means of communication is for hormones to carry signals to tissues about our dietary state. For example, a message that we have just had a meal, carried by the hormone insulin, signals adipose tissue to store fat.

2

SECTION I

Fuels: Carbohydrate Fat Protein

Fuel Metabolism

Vitamins Minerals H20

I Xenobiotics Digestion absorption, transport

Biosynthetic pathways

Fuel storage pathways

Body components

F I G U RE 1. 1 An overview of the general metabolic routes for dietary components in the body. The types of pathways are named in red.

In the following section, we will provide an overview of various types of dietary components and examples of the pathways involved in using these com­ ponents. We will describe the fuels in our diet, the compounds produced by their digestion, and the basic patterns of fuel metabolism in the tissues of our bodies. We will describe how these patterns change when we eat, when we fast for a short time, and when we starve for prolonged periods. Patients with medical problems that involve an inability to deal normally with fuels will be introduced. These patients will appear repeatedly throughout the book and will be j oined by other patients as we delve deeper into biochemistry. It is important to note that this section of the book contains an overview of basic metabolism, which allows patients to be presented at an elementary level and to whet students ' appetites for the biochemistry to come. The goal is to enable the student to taste and preview what biochemistry is all about. It is not designed to be all-inclusive, as all of these topics will be discussed in greater detail in Sections IV through VII of the text. The next section of the text (Section II) begins with the basics of biochemistry and the relationship of basic chemistry to processes that occur in all living cells .

Metabolic Fuels and Dietary Components

Fuel Metabol ism. We obtain our fuel primarily from the macronutrients (i.e., carbohyd rates, fats, and proteins) in our d i et. As we eat, our foodstuffs are digested and absorbed. The products of d igestion circulate in the blood, enter vari­ ous tissues, and are eventual ly taken u p by cel ls and oxid ized to produce energy. To completely convert our fuels to carbon d i oxide (C02) and water (H 20) , molecu lar oxygen (02) is req u i red. We breathe to obtain th is oxygen and to e l i m i nate the C02 that is produced by the oxidation of our foodstuffs. Fuel Stores. Any d i etary fuel that exceeds the body's i m med iate energy needs is stored, mai n ly as triacylglycerol (fat) i n ad i pose tissue, as glycogen (a carbo­ hyd rate) in muscle, l iver, and other cells, and, to some extent, as protein i n muscle. When we are fasting, between meals and overn ight wh i l e we sl eep, fuel is d rawn from these stores and is oxid ized to provide energy (Fig. I . I ) . Fuel Req uirements. We req u i re enough energy each day to d rive the basic fu nctions of our bod ies and to support our physical activity. If we do not consume enough food each day to supply that much energy, the body's fuel stores supply the remai nder and we lose weight. Conversely, if we consume more food than req u i red for the energy we expend, our body's fuel stores enlarge and we gai n weight. Other Dietary Req u i rements. In add ition to provid i ng energy, the d i et provides precu rsors for the biosynthesis of compounds necessary for cel l u lar and tissue structu re , fu nction, and survival. Among these precu rsors are the essential fatty acids and essential am ino acids (those that the body needs but can not synthesize) . The d i et must also supply vitam ins, minerals, and water. Waste Disposal. D i etary components that we can use are referred to as nutrients. However, both the d i et and the air we breathe contain xenobiotic compounds, compounds that have no use or val ue i n the h u man body and may be toxic .These com­ pounds are excreted i n the urine and feces together with metabo l i c waste products.

Excess dietary fuel Fed

!

Fasting

I

Fuel stores: Fat G lycogen Protein Oxidation

F I G U RE 1 . 1 states.

Fate of excess d ietary fuel i n fed and fasting

�

' �

-Energy

, � ' "'-

3

4

SECTION I

Fuel Metabolism

T H E WA I T I N G ROOM

--

-·----- - ---···

Percy V. is a 59-year-old school teacher who was in good health until his

wife died suddenly. Since that time, he has experienced an increasing de­ gree of fatigue and has lost interest in many of the activities he previously enjoyed. Shortly after his wife's death, one of his married children moved far from home. Since then, Mr. V. has had little appetite for food. When a neighbor found Mr. V. sleeping in his clothes, unkempt, and somewhat confused, she called an am­ bulance. Mr. V. was admitted to the hospital psychiatry unit with a diagnosis of mental depression associated with dehydration and malnutrition. Otto S. is a 25-year-old medical student who was very athletic during high

Heat Energy utilization

Energy production via oxidation of

Biosynthesis Detoxification M uscle contraction Active ion transport Thermogenesis

Carbohydrate Lipid

P rotei n

ADP

+

p.I

/

F I G U RE 1 .2 The ATP-AD P cycle. The energy-generati ng pathways are shown i n red; the energy-util izing pathways in blue. ATP, ad­ enosine tri phosphate; ADP, adenosine diphos­ phate; P;, inorganic phosphate.

school and college but is now out of shape. Since he started medical school, he has been gaining weight. He is 5 ft 10 in tall and began medical school weighing 1 54 lb, within his ideal weight range. By the time he finished his last ex­ amination in his first year, he weighed 1 87 lb. He has decided to consult a physician at the student health service before the problem gets worse, as he would like to reduce his weight (at 1 87 lb, his body mass index [BMI] is 27] to his previous level of 1 54 lb (which would reduce his BMI to 23, in the middle of the healthy range of BMI values). Ivan A. is a 56-year-old accountant who has been obese for a number of years.

He exhibits a pattern of central obesity, called an "apple shape," which is caused by excess adipose tissue being disproportionally deposited in the abdominal area. His major recreational activities are watching TV while drinking scotch and soda and doing occasional gardening. At a company picnic, he became very "winded" while playing softball and decided it was time for a general physical examination. At the ex­ amination, he weighed 264 1b at 5 ft 1 0 in tall. His blood pressure was elevated, 155 mm Hg systolic and 95 mm Hg diastolic (for Ivan's age, hypertension is defined as > 1 40 mm Hg systolic and >90 mm Hg diastolic). For a male of these proportions, a BMI of 1 8.5 to 24.9 would correspond to a weight between 1 29 and 173 lb. Mr. A. is almost 1 00 lb overweight, and his BMI of 37.9 is in the range defined as obesity. Ann R. is a 23-year-old buyer for a woman's clothing store. Despite the fact

L

Fatty acids Glucose

Amino acids

e-�Acetyi-CoA * �:Ae-

that she is 5 ft 7 in tall and weighs 99 lb, she is convinced she is overweight. Two months ago, she started a daily physical activity program that consists of 1 hour of jogging every morning and 1 hour of walking every evening. She also decided to consult a physician about weight loss. If patients are above (like Ivan A.) or below (like Ann R.) their ideal weight, the physician, often in consultation with a registered dietitian, prescribes a diet designed to bring the weight into the ideal range.

--- · ----------- ------

--------------- ------

1. D i etary Fue l s

-'.�:�'

! � ;; � � �� -

ain

H20

02

F I G U RE 1 .3 Generation of ATP from fuel components d u ring respiration. G l ucose, fatty acids, and amino acids are oxid ized to acetyl coenzyme A (acetyi-CoA), a su bstrate for the tricarboxylic acid (TCA) cycle. In the TCA cycle, they are completely oxid ized to C0 2 • As fuels are oxid ized, electrons (e - ) are trans­ ferred to 0 2 by the electron transport chain, and the energy is used to generate ATP.

The maj or fuels w e obtain from our diet are the macronutrients-namely, carbo­ hydrates, proteins, and fats. When these fuels are oxidized to C02 and H2 0 in our cells (the process of catabolism), energy is released by the transfer of electrons to 02 . The energy from this oxidation process generates heat and adenosine triphos­ phate (ATP) (Fig. 1 .2). C0 2 travels in the blood to the lungs where it is expired, and water is excreted in urine, sweat, and other secretions. Although the heat that is generated by fuel oxidation is used to maintain body temperature, the main purpose of fuel oxidation is to generate ATP. ATP provides the energy that drives most of the energy-consuming processes in the cell, including biosynthetic reactions (anabolic pathways), muscle contraction, and active transport across membranes . As these processes use energy, ATP is converted back to adenosine diphosphate (ADP) and inorganic phosphate (PJ The generation and use of ATP is referred to as the ATP­ ADP cycle. The oxidation of fuels to generate ATP is called respiration (Fig. 1 .3 ) . Prior to oxidation, carbohydrates are converted principally to glucose, fat to fatty acids,

I

0-0-CI Co-0 ---

---

HO

HO

HO

C_H_2 ,

HO

Starch (diet)

or

_,

HO

Metabolic Fuels and Dietary Components

5

0H0 �/H-- \� c yH 2

0-- ...... HO\

Excreted N

Nitrogen balance

Normal healthy adult

Dietary N

=

Excreted N

Negative nitrogen balance

Dietary deficiency of total protein or amino acids: catabolic stress

Dietary N