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Biochemistry FIRST CANADIAN EDITION Reginald H. Garrett University of Virginia Charles M. Grisham University of Virginia Stavroula Andreopoulos University of Toronto William G. Willmore Carleton University Imed E. Gallouzi McGill University With molecular graphic images by Michal Sabat, University of Virginia NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. This is an electronic version of the print textbook. Due to electronic rights restrictions, some third party content may be suppressed. Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. The publisher reserves the right to remove content from this title at any time if subsequent rights restrictions require it. For valuable information on pricing, previous editions, changes to current editions, and alternate formats, please visit www.cengage.com/highered to search by ISBN#, author, title, or keyword for materials in your areas of interest. Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Biochemistry, First Canadian Edition by Reginald H. Garrett, Charles M. Grisham, Stavroula Andreopoulos, William G. Willmore, and Imed E. Gallouzi Vice President, Editorial Production Service: Managing Designer: Higher Education: Integra Software Services Franca Amore Anne Williams Copy Editors: Interior Design: Publisher: Frances Robinson and Julia Lisa Devenish Paul Fam Cochrane Cover Design: Marketing Manager: Proofreader: Sasha Moroz Leanne Newell Erin Moore Cover Image: Developmental Editor: Indexer: David Bushnell, Kenneth Westover, Candace Morrison Alan Yoshioka and Roger Kornberg Photo Researcher and Permissions Production Coordinator: Compositor: Coordinator: Lynn McLeod Ferial Suleman Integra Software Services Content Production Manager: Design Director: Printer: Jennifer Hare Ken Phipps RR Donnelley COPYRIGHT © 2013 by Nelson ALL RIGHTS RESERVED. No part of Library and Archives Canada Education Ltd. this work covered by the copyright Cataloguing in Publication Data herein may be reproduced, Adapted from Biochemistry, Fourth transcribed, or used in any form or Biochemistry / Reginald H. Edition, by Reginald H. Garrett and by any means—graphic, electronic, Garrett ... [et al.].—1st Canadian ed. Charles M. Grisham, published by or mechanical, including Brooks/Cole, Cengage Learning. Includes index. photocopying, recording, taping, Copyright ©2010 by Brooks/Cole, ISBN 978-0-17-650265-2 Web distribution, or information Cengage Learning. storage and retrieval systems— 1. Biochemistry—Textbooks. Printed and bound in the without the written permission of I. Garrett, R. (Reginald) United States the publisher. QD415.B538 2012 572 1 2 3 4 15 14 13 12 For permission to use material C2012-905998-6 For more information contact from this text or product, submit Nelson Education Ltd., all requests online at ISBN-13: 978-0-17-650265-2 1120 Birchmount Road, Toronto, www.cengage.com/permissions. ISBN-10: 0-17-650265-3 Ontario, M1K 5G4. Or you can visit Further questions about our Internet site at permissions can be emailed to http://www.nelson.com [email protected] Every effort has been made to trace ownership of all copyrighted material and to secure permission from copyright holders. In the event of any question arising as to the use of any material, we will be pleased to make the necessary corrections in future printings. NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Dedication To Georgia —R.H.G. To Rosemary —C.M.G. To Agni —S.A. To my parents and family —W.G.W. To my wife Kerrie-Ann Trudeau and my son Jackson, with love —I.E.G. NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. About the Authors Reginald H. Garrett was educated in the Baltimore city public Charles M. Grisham was born and raised in Minneapolis, schools and at the Johns Hopkins University, where he received Minnesota, and educated at Benilde High School. He received his Ph.D. in biology in 1968. Since that time, he has been at the his B.S. in chemistry from the Illinois Institute of Technology in University of Virginia, where he is currently Professor of Biology. 1969 and his Ph.D. in chemistry from the University of Minnesota He is the author of previous U.S. editions of Biochemistry, as in 1973. Following a postdoctoral appointment at the Institute well as Principles of Biochemistry (Cengage, Brooks/Cole), and for Cancer Research in Philadelphia, he joined the faculty of the numerous papers and review articles on the biochemical, genetic, University of Virginia, where he is Professor of Chemistry. He is and molecular biological aspects of inorganic nitrogen metabolism. the author of previous editions of Biochemistry and Principles of His research interests focused on the pathway of nitrate assimilation Biochemistry (Cengage, Brooks/Cole), and numerous papers and in fi lamentous fungi. His investigations contributed substantially review articles on active transport of sodium, potassium, and cal- to our understanding of the enzymology, genetics, and regulation cium in mammalian systems, on protein kinase C, and on the appli- of this major pathway of biological nitrogen acquisition. More cations of NMR and EPR spectroscopy to the study of biological recently, he has collaborated in systems approaches to the meta- systems. He has also authored Interactive Biochemistry CD-ROM bolic basis of nutrition-related diseases. His research has been sup- and Workbook, a tutorial CD for students. His work has been sup- ported by the National Institutes of Health, the National Science ported by the National Institutes of Health, the National Science Foundation, and private industry. He is a former Fulbright Scholar Foundation, the Muscular Dystrophy Association of America, the at the Universität fur Bodenkultur in Vienna, Austria, and served Research Corporation, the American Heart Association, and the as Visiting Scholar at the University of Cambridge on two separate American Chemical Society. He is a Research Career Development occasions. During the second, he was Thomas Jefferson Visiting Awardee of the National Institutes of Health, and in 1983 and Fellow in Downing College. In 2003, he was Professeur Invité at the 1984 he was a Visiting Scientist at the Aarhus University Institute Université Paul Sabatier/Toulouse III and the Centre National de la of Physiology Denmark. In 1999, he was Knapp Professor of Recherche Scientifi que, Institute for Pharmacology and Structural Chemistry at the University of San Diego. He has taught bio- Biology in France. He has taught biochemistry at the University of chemistry and physical chemistry at the University of Virginia for Virginia for more than 40 years. He is a member of the American 37 years. He is a member of the American Society for Biochemistry Society for Biochemistry and Molecular Biology. and Molecular Biology. Garrett Georgia Cobb Charles M. Grisham and Reginald H. Garrett NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Stavroula Andreopoulos, Ph.D., is a Senior Lecturer and Acting awards, including an Ontario Early Researcher Award and a Undergraduate Coordinator in the department of Biochemistry at Graduate Mentorship Award. the University of Toronto. She is a passionate teacher who coordi- nates second- and third-year undergraduate Biochemistry courses with over 1700 students registered from a wide variety of programs. She earned her M.Sc. and Ph.D. at the University of Toronto. While she began her work in biochemical research at the University of Athens and the Centre for Addiction and Mental Health examining both the molecular mechanisms aspects of soluble guanylyl cyclase and lithium regulation of TRPC ion channels in bipolar disorder, her primary interest and love is now teaching. She is the recipient of several awards, including the NCDEU New Investigator’s Award; the Centre for Addiction and Mental Health (CAMH) Fellowship Award; and, more recently, the Excellence in Undergraduate Teaching in Life Sciences Award from the University of Toronto in 2011. William G. Willmore Imed-Eddine Gallouzi, Ph.D., is an Associate Professor in the Department of Biochemistry at McGill University. He is also a Tier 2 Canada Research Chair in Cellular Information Systems. In 1998, he obtained his Ph.D. in Molecular and Celluar Biology from the Université Montpellier 2, Sciences et Techniques. His primary area of research is in Messenger RNA (mRNA), the stability of which infl uences gene expression in virtually all organisms, with a focus on mammals. His laboratory specializes in the study of RNA binding proteins and the various roles they play in physiological and pathological processes. He focuses on delineating the regula- tory mechanisms that modulate mRNA expression during cell death and muscle formation. He is also testing the use of chemicals to interfere with muscle wasting induced by various diseases such as cancer, AIDS, and sepsis. His program at McGill University creates Stavroula Andreopoulos a new centre of excellence in cell biology at the institution, and his training activities have generated a strong team of cross-disciplinary William G. Willmore, Ph.D., is an Associate Professor and the cur- researchers who bring expertise in biochemistry, cell biology, and rent Chair of the Institute of Biochemistry at Carleton University. molecular biology technologies to bear on the challenging problems In 1997, he obtained his Ph.D. in Biochemistry at Carleton and did related to cancer cell development and growth. postdoctoral research at Brigham and Women’s Hospital, Harvard Medical School, in Boston, Massachusetts. He is the instructor for many third-year Biochemistry courses at Carleton, where he also leads a multidisciplinary team of researchers examining the role of protein posttranslational modifi cations in response to stress, p rimarily low oxygen (hypoxia) and oxidative stresses. He has estab- lished a Facility for Free Radical Research at Carleton, investigating protein structure/function modifi cation in response to oxygen. His research attempts to discover novel therapeutics in ischemic car- diovascular diseases, such as cardiac arrest and stroke, as well as aging, have attracted international attention, including invited talks at Gordon Research Conferences. He is the recipient of numerous Imed-Eddine Gallouzi NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Contents in Brief PART I: Building Blocks of the Cell 1 1. The Facts of Life: Chemistry Is the Logic of Biological Phenomena 1 2. Water: The Medium of Life 32 3. Thermodynamics of Biological Systems 53 4. Amino Acids 75 5. Proteins: Their Primary Structure and Biological Functions 98 6. Proteins: Secondary, Tertiary, and Quaternary Structure 140 7. Carbohydrates and the Glycoconjugates of Cell Surfaces 189 8. Lipids 228 9. Lipid Biosynthesis 252 1 0. Membranes and Membrane Transport 299 1 1. The Reception and Transmission of Extracellular Information 349 PART II: Protein Dynamics 403 12. Enzymes—Kinetics and Specifi city 403 13. Mechanisms of Enzyme Action 442 1 4. Enzyme Regulation 477 1 5. Molecular Motors 505 PART III: Metabolism and Its Regulation 537 16. Nutrition and the Organization of Metabolism 537 17. Glycolysis 561 1 8. The Tricarboxylic Acid Cycle 591 1 9. Electron Transport and Oxidative Phosphorylation 621 2 0. Photosynthesis 659 21. Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate Pathway 693 22. Fatty Acid Catabolism 735 23. Nitrogen Acquisition and Amino Acid Metabolism 761 PART IV: Nucleic Acids 808 24. Nucleotides and Nucleic Acids 808 25. Structure of Nucleic Acids 833 26. Synthesis and Degradation of Nucleotides 871 27. Recombinant DNA: Cloning and Creation of Chimeric Genes 897 2 8. DNA Metabolism: Replication, Recombination, and Repair 926 PART V: Information Transfer 963 29. Transcription and the Regulation of Gene Expression 963 30. Protein Synthesis 1009 31. Post-transcriptional Regulation of Gene Expression: mRNA Turnover and Micro-RNA 1048 32. Completing the Protein Life Cycle: Folding, Processing, and Degradation 1086 33. Metabolic Integration and Organ Specialization 1109 NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Detailed Contents About the Authors iv Archaea and Bacteria Have a Relatively Simple Structural Organization 19 Preface xxix The Structural Organization of Eukaryotic Cells Is More Laboratory Techniques in Biochemistry xl Complex Than That of Prokaryotic Cells 21 1.6 What Are Viruses? 23 1.7 Do Biomolecules Ever Behave as Genetic Agents? 26 PART I Building Blocks of the Cell Prions and Viroids Can Act as Genetic Agents 26 SUMMARY 29 1 The Facts of Life: Chemistry Is the Logic of PROBLEMS 30 Biological Phenomena 1 FURTHER READING 31 1.1 What Are the Distinctive Properties of Living 2 Water: The Medium of Life 32 Systems? 2 2.1 What Are the Properties of Water? 33 1.2 What Kinds of Molecules Are Biomolecules? 5 Water Has Unusual Properties 33 Biomolecules Are Carbon Compounds 6 Hydrogen Bonding in Water Is Key to Its 1.3 What Is the Structural Organization of Complex Properties 34 Biomolecules? 6 The Structure of Ice Is Based on H-Bond Formation 34 Metabolites Are Used to Form the Building Blocks Molecular Interactions in Liquid Water Are Based on of Macromolecules 6 H Bonds 35 Membranes Are Supramolecular Assemblies That The Solvent Properties of Water Derive from Its Polar Defi ne the Boundaries of Cells 10 Nature 35 The Unit of Life Is the Cell 10 Water Can Ionize to Form H! and OH" 39 1.4 How Do the Properties of Biomolecules Refl ect 2.2 What Is pH? 40 Their Fitness to the Living Condition? 10 Strong Electrolytes Dissociate Completely in Biological Macromolecules and Their Building Blocks Water 41 Have a “Sense” or Directionality 11 Weak Electrolytes Are Substances That Dissociate Only Biological Macromolecules Are Informational 11 Slightly in Water 42 Biomolecules Have Characteristic Three-Dimensional The Henderson–Hasselbalch Equation Describes the Architecture 12 Dissociation of a Weak Acid in the Presence of Its Weak Forces Maintain Biological Structure and Conjugate Base 43 Determine Biomolecular Interactions 12 Titration Curves Illustrate the Progressive Dissociation Hydrogen Bonds Are Important in Biomolecular of a Weak Acid 44 Interactions 13 Phosphoric Acid Has Three Dissociable H! 45 The Defi ning Concept of Biochemistry Is “Molecular Recognition Through Structural 2.3 What Are Buffers and What Do They Do? 46 Complementarity” 14 The Phosphate Buffer System Is a Major Intracellular Biomolecular Recognition Is Mediated by Weak Buffering System 46 Chemical Forces 15 Dissociation of the Histidine–Imidazole Group Also Weak Forces Restrict Organisms to a Narrow Range Serves as an Intracellular Buffering System 47 of Environmental Conditions 16 “Good” Buffers Are Buffers Useful within Physiological Enzymes Catalyze Metabolic Reactions 17 pH Ranges 47 The Time Scale of Life 17 HUMAN BIOCHEMISTRY: The Bicarbonate Buffer System of Blood Plasma 48 1.5 What Is the Organization and Structure of Cells? 17 HUMAN BIOCHEMISTRY: Blood pH and The Evolution of Early Cells Gave Rise to Eubacteria, Respiration 49 Archaea, and Eukaryotes 18 What Are Common Buffers Used in Biochemistry? 49 How Many Genes Does a Cell Need? 18 NEL Copyright 2012 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it.