[ xiv] Pre fac e r-. 1A Genetic Foundations 27 Genetic Continuity Is Ves ted in Single DNA Molecules 27 The Struc tu re of DNA Allows for Its Replication and Repair with Near-Perfect.Fidelity 28 The Linear Sequ ence in DNA Encodes Proteins with Three-Dimensional Structures 29 1.1 Cellular Foundations 2 Cells Are t he Structural and Functional Units of All Living Organisms 3 Cellular Dimens ions Are Limited by Diffusion There Are Three Distinct Domains of Life 4 Escherichia coli Is the Most-Studied Bacterium 5 Eukaryotic Cells Have a Variety of Membra nous Organelles, Which Can Be Isolated for Study 7 The Cytoplasm Is Organized by the Cytoskeleton and Is Highly Dynamic 8 Cells Build Supramolecular Structures n In Vitro Studies May Overlook Important Interactions among Molecu les 10 1 1 The Foundations ofB iochemi stry 1.2 Chemical Foundations 11 Biomolecules Are Compounds of Carh on with a Variety of Fun ctional Groups 11 Cells Contain a Universal Set of Small Molecules 13 Box 1-1 Molecular Weight, Molecular Mas s,and T heir Correct Units 14 Macromolecules Are the Major Constituen ts of Cells 14 Three-Dimensional Structure Is Described by Configuration and Conformation 15 Box 1-2 louis Pasteur and Optical Activity: In V ino , Veritas 17 Int eractions between Biorno leculos Are Stereospecific 18 1.3 Physical Foundations 19 Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their Surroundings 20 Organisms T ran sform Energy and Matter from Their Surroundings 20 Box 1-3 Entropy: The Ad vantagesofBe ing Di sorganized 21 The Flow of Electrons Provides Energy for Organisms 22 Creating and Maintaining Order Requires Work and Energy 22 Energy Coupling Links Reactions in Biology 22 [{ I' ll and .1Go Are Measures of a Reaction's Tendency to Proceed Spontaneously 24 Enzymes Promote Sequences of Chemical Reac tions 25 Metabolism Is Regulated to Achieve Balance and Economy 26 Preface v iii The Foundations of Biochemistry I STRUCTURE AND CATALYSIS 41 2 Water 43 3 Amino Aclds, Peptides, an d Prote ins 71 4T he Ihree-Dimens ional Struct u re of Proteins 113 5 Protein Function 153 6 Enzymes 1B3 7 Carbohydrates and Glycobio logy 235 B Nucleotides a nd Nucle ic Aclds 271 9 DNA-Based Info rmation Techno log ies 303 10 Lipids 343 11 Biological Membranes and Transport 371 12 Biosigna ling 417 II BIOENERGETICS AND METABOLISM 48S 13 Bioenergetics a nd B iochemical Reaction Types 489 14 Glycolysis, G l uconeogenes is,and the Pentose Phosphate Pathway 527 15 Princlples of Metabolic Regula tion 569 16 The Citric Acid Cycle 6 15 17 FattyAcld Cata bolism 647 18 Amino Acld Ox idatio n and the Productio n of Urea 673 19 Oxidat ive Phosp ho ry lation an d Photo p hosphory lat ion 707 20 Ca rbo hyd rate Biosynthesis in Pl ants an d Bacteria 773 21 Lipid Biosynt hesis 8 05 22 Bi osyn thesis of Ami no Aclds, N ucl eotldes,and Relate d Mo lecules 85 1 23 Hormona l Regulation and Integ rat io n of Mam malia n Metabolism 901 III INFORMATION PATHWAYS 945 24 Genes an dC hromosomes 947 25 DNA Metabo lism 975 26 RNA Metabolism 1021 27 Protein Meta bo lism 1 065 28 Reg u lation of Gene Exp ress io n 1115 Conte nts in B rie Appendix ACommon Abbreviationsin the Biochemical Res earch Literature A-I Appendix BAbbreviatedSolutions to ProblemsAS-I Glossary G- I Credits C- I IndexI -I Scott C. Mohr, Boston U niversity Kimberly Mowry, Brown University Leisha Mullins, Texas A&MUniversity Sewite Negash, California State University, Long Beach Allen W.Nicholson, Temple Univers ity Hiroshi Nikaido, University oj California, Berkeley James Ntambi, University oj Wisconsin-1Vfadison Timothy F. Os borne, University of California, Iruine Jose R. I'erez-Casttneira, Univ ersi ty oj Seville, Sp ain Ter ry Platt, Univ er sity qf Rochester We ndy Pogozelski, State Unioersitu oj New York at Geneseo Jon athan Poppe r, Univ ersi ty oj Wisconsin-Madison Thom as Poulos, University oj California, Irvine Jack Preiss, Micniaan State Univers ity Anna Radominsk a-Pandya, University oj Arkansas Ron Raines, University QfWisconsin-Madison Tom A. Rapoport, Harvard Medical School Jas on J. Reddick, University oj North Carolina, Greensboro Mary Roberts, Boston College Ingrid K. Ruf Univ er sity oj Calif ornia, Irvine Aboozar Soleirnan t, Tehran U niv ersi ty, Ir an Mark Spaller, Wayne State Unio ersuu Step hen Spiro, University of Tex as at Dallas Narasimha Sreerama, Colorado State University Jon D. Stewar t, University oj Florida Koni Stone, California State Unioersuu, Stanislaus Jon H. St ult zfus, Michigan State University Jeremy Thorner, University of California, Berkeley Dean R. Tolan, Boston University Sandr a 1. Turchi, Millersville University Manuel Varela, Eastern New Mexico University Bob Warburt on , Shepherd University Tracy Ware, Salem Stale College Susan Weintra ub, University oj T e:ras, Health Science Center Michael Yaffe, Massacnusetts Institute of Techn ology We lac k th e s pace here to acknowledge all the other individuals wh ose s pecial efforts went into this book. We offer instead our sincere t hanks -and th e finished book that they helped guide to comp let ion. We, of co urse ,a ssume full resp onsibility for errors at fact or emphasis. We want especially to thank our students at the- University of Wisconsin-Madison for their numerous com- ments and suggestions. If something in the book does not work, tliey are never shy about letting us know it. We are grateful to the stu dents and staff of our research groups and of the Center for Biology Education, who helped us balance the competing demands on our time; to our colleagues in the Department of Biochemistry at t. he University of Wisconsin-Madison, who helped us with advice and criticism; and tothe many students and teachers who have written to suggest ways of improving the book. We hope our readers will continue to provide input for future editions. Finally, we ex press our deepest ap preciation to our wives, Brook and Beth, and our families, who sho wed extraordinary patience with, and supp ort for, our book writing. David L. Nelson Michael Ivl. Cox Madison, Wisconsin J anuary 2008 colleague. We feel very fortunate to have such gifted part- ners as Brook, Shelley,Adam, and Jean-Yves on our team. We are also deeply indebted to Brian White of the Uni- versity of Massa chusetts-Boston, who wrote the new data analysis problems at the end of each chapter. Many colleagues played a spec ial role through their inte rest in the pr oject and their timely input. Prominent among these are Laurens And erson of the University of Wisconsin- Madison; Jeffrey D. Esko of the University of California, San Diego; Jack Kirsch and his students at the University of California, Berkeley; and Dana Aswad, Shiou-Chuan (Sheryl) Tsai, Michael G. Cumsky, and the ir colleag ues (listed below) at the University of California, Irvine . Many others he lped us shape this fif th edition with their comments, suggestions,and criticisms. To all of them, we are deeply grateful: Richard M. Amasino, University of Wisconsin-Madison Louise E. Anderson, University oj Illinois at Chicago Cheryl Bailey, Univ ersity oj Nebraska, Lincoln Kenneth Balazovich, University oj Michigan Thomas O. Baldwin, Unive rsity oj A rizon a Vahe Bandarian, University of Arizona Eugene Barber, University oj Rochester Sebasti an Y . Bednarek, Univ ersity oj Wisconsin-Madison. Ramachandra Bhat, Lincoln University J ames Blankenship, Corne tt University Sandra J. Bonetti , Colorado State University, Pueblo Barbara Bowman, University oj California, Berkeley Scott D. Briggs , Purdue Unive rsity Jeff Brodsky, University oj Pitt sburgh Ben Cald well, Missouri Western State University David Camerini, Univ er sity of California, Irvine Guillaume Chanfreau , U niversity oj California, Los Angeles Melan ie Coccal University oj California) Irvine Je ffrey Cohlberg, Calif ornia State University, Long Beach Kim D. Collins, University of Maryl and Charles T. Dameron, Duquesne University Ric hard S. Eise nstein, University oj Wisconsin-Madison Gerald W. Feigenso n, Cornell Univers ity Robert H. Fillingame, University of Wisconsin-Madison Brian Fox, Unio ersuu Of Wisconsin-Madison Gerald D. Frenkel, Rutgers University Perry Frey, University oj Wisconsin-Madison David E. Grah am , Uruoersitu of Texas- Austin William J. Gr imes, Univers ity O f Arizona Martyn Gunn, Texas A&M Univ ersity Olivia Hanson, University oj Central Oklahoma Amy Hark, Muhlenbe rg College Shaun V. Hernandez, University OfWisconsin-Madison Peter Hinkle, Cornell Univ er sity P. Shing Ho, Oreg on Stat e Unive rsily Charles G. Hoogstraten, Afichigan State Univers ity Gerwald Jogl. Brown Univers ity Sir Hans Kornberg, Boston University Bob Landick, U niversity oj Wisconsin-Madison Patrick D. Larkin, Texas A&M Unioersuu, Corpus Christi Ryan P. Liegel, Univ ers ity of Wisconsin-Madison Maria Linder, California State University, Fullerton Andy C. Lawang. Texas A&MUniversity John M akemson, Florid a Int ernational University JohnC. Matthews, Uniuereitu ojMt, ,,iBsi ppi , School ojPharmacu Benjamin J. McFarland, Seattl e Pacific Uniuersiu) Anant Menon, W eill Cornell Med ical College Sabeeha Mercha nt , Unioersiiu oj Calif ornia, Los Angeles