[ xiv] Preface

r-.

1A Genetic Foundations 27Gene tic Continu ity Is Ves ted in Single

DNA Molecules 27The St ruc tu re of DNA Allows for Its Replication

and Repair wit h Near-Pe rfect. Fidelity 28The Line ar Sequence in DNA Encodes Proteins with

Three-Dimensional Structu re s 29

1.1 Cellular Foundations 2Cells Are the Structural and Functional

Units of All Living Organisms 3Cellular Dimens ions Are Limited by Diffusion ~3

There Are Three Dist inct Domains of Life 4Escherichia coli Is the Most -St udied Bacterium 5Eukaryotic Cells Have a Variet y of Membra nous

Organel les , Which Can Be Isolated for Study 7The Cytoplasm Is Organized by th e Cytoskeleton

and Is Highly Dynamic 8Cells Build Supramolecular St ruct ures nIn Vitro Studies May Overlook Important

Interactions among Molecu les 10

11 The Foundations ofBiochemistry

1.2Chemical Foundations 11Biomolecules Are Compounds of Carh on with

a Varie ty of Functional Groups 11Cells Contain a Universal Set of Small Molecules 13

Box 1-1 Molecular Weight,Molecular Mass,andTheir Correct Units 14Macromolecules Are the Major

Const ituen ts of Cells 14Three-Dimensiona l Stru cture Is Described

by Configuration and Conformation 15

Box 1-2 louis Pasteur and Optical Activity:In Vino, Veritas 17In teractions between Biorno lecu los

Are Stereospecific 18

1.3 Physical Foundations 19Living Organisms Exist in a Dynam ic

Steady Stat e, Never a t Equilibrium withTheir Surroundings 20

Organisms Transform Energy and Matterfrom Their Surroundings 20

Box 1-3 Entropy:The AdvantagesofBeing Disorganized 21The Flow of Electrons Provides Energy

for Organisms 22Creating and Maintaining Order Requires Work

and Energy 22Energy Coupling Links Reactions in Biology 22[{I' ll and .1GoAre Measures of a Reac tion's

Ten dency to Proceed Spontaneously 24Enzymes Promote Sequences of Chemical Reac tions 25Metabolism Is Regulated to Achieve Balance

and Econo my 26

Preface viii

The Foundations of Biochemistry

I STRUCTURE AND CATALYSIS 412 Water 433 Amino Aclds, Peptides, andProteins 71

4 The Ihree-Dimensional Structure of Proteins 1135 Protein Function 1536 Enzymes 1B37 Carbohydrates and Glycobiology 235B Nucleotides and Nucleic Aclds 2719 DNA-Based Information Technologies 30310 Lipids 34311 Biological Membranesand Transport 37112 Biosignaling 417

II BIOENERGETICS AND METABOLISM 48S13 Bioenergetics and Biochemical Reaction Types 48914Glycolysis, Gluconeogenesis,and the Pentose

PhosphatePathway 52715 Princlples of Metabolic Regulation 56916 The Citric Acid Cycle 61517 FattyAcldCatabolism 64718 Amino Acld Oxidationand the Productionof Urea 67319 Oxidative Phosphorylation andPhotophosphorylation 70720 Ca rbohydrate Biosynthesis in PlantsandBacteria 77321 Lipid Biosynthesis 80522 Biosynthesis of Amino Aclds, Nucleotldes,and

RelatedMolecules 85123 HormonalRegulation and Integrationof

MammalianMetabolism 901

III INFORMATION PATHWAYS 94524 Genes andChromosomes 94725 DNA Metabolism 97526 RNA Metabolism 102127 Protein Metabolism 106528 Regulation of Gene Exp ression 1115

Contentsin Brie

Appendix ACommon Abbreviationsin theBiochemical

Research Literature A- I

Appendix BAbbreviatedSolutions to ProblemsAS- IGlossary G- I

Credits C- I

IndexI-I

Scott C. Mohr, Boston UniversityKimberly Mowry, Brown UniversityLeisha Mullins, Texas A&M Univ ersitySewite Negash, California State University, Long BeachAllen W. Nicholson, Temple Univ ersityHiroshi Nikaido , University oj California, BerkeleyJames Ntambi, Universi ty oj Wisconsin-1VfadisonTimothy F. Osborne , University ofCalifornia, IruineJose R. I'erez-Casttneira, Univ ersi ty oj Seville, SpainTer ry Platt, Univ ersity qfRochesterWendy Pogoze lski, State Unioersi tu oj New York at GeneseoJonathan Popper, Univ ersi ty oj Wisconsin-MadisonThom as Poulos, University ojCaliforn ia, IrvineJack Preiss , Micniaan State UniversityAnna Radominska-Pandya, Univ ersity oj ArkansasRon Raines, Univ ersity QfWisconsin-MadisonTom A. Rapoport, Harvard Medi cal SchoolJason J. Reddick, University ojNor th Carolina, GreensboroMary Roberts , Boston CollegeIngrid K. Ruf Univ ersity oj California, IrvineAboozar Soleirnan t, Tehran Universi ty, IranMark Spaller , Wayne State UnioersuuStephen Spiro, Universi ty of Tex as at DallasNarasimha Sreerama, Colorado Stat e UniversityJon D. Stewart, Univ ersity oj FloridaKoni Stone, California State Unioersuu, StanislausJon H. Stultzfus, Michigan State Un iversityJeremy Thorn er, Unive rsity of California, BerkeleyDean R. Tolan, Boston Univ ersitySandr a 1. Turchi , Millersville Univ ersityManuel Varela, Eastern New Mexico UniversityBob Warburt on , Shepherd Un iversi tyTracy Ware, Salem Stale CollegeSusan Weintra ub, University oj Te:ras, Health Science CenterMichael Yaffe, Massacnusetts Ins titute of Technology

We lac k th e space here to acknowledge all the othe rindividuals whose special effort s went int o this book.We offer inst ead our sincere thanks-and th e finishedbook that they help ed guide to completion. We, ofcourse, assume full resp onsibility for errors at fact oremphasis.

We want especially to thank our students at the­University of Wisconsin- Madison for their numerous com­ments and suggestions. If something in the book does notwork, tliey are never shy about letting us know it. We aregrateful to the students and staff of our research groups andof the Center for Biology Education, who helped us balancethe competing demands on our time; to our colleagues inthe Department of Biochemistry at t.he University ofWisconsin-Madison, who helped us with advice and criticism;and to the many students and teachers who have writt en tosuggest ways of improving the book. We hope our readerswill continue to provide input for future editions.

Finally, we express our deep est appreciation to ourwives , Brook and Bet h, and our families, who showedex traordinary patience with, and support for , our bookwriting.

David L. NelsonMichael Ivl. Cox

Madison , WisconsinJanuary 2008

colleague. We feel very fortunate to have such gifted part­ners as Brook, Shelley,Adam, and Jean-Yves on our team.

We are also deeply indebted to Brian White of the Uni­versity of Massachusetts- Bosto n, who wrote th e newdata analysis problems at the end of each chapter.

Many colleagues played a special role through theirinte rest in the project and their timely input. Prominentamong these are Laurens Anderson of the Universityof Wisconsin- Madison; Jeffrey D. Esko of the University ofCalifornia, San Diego; Jack Kirsch and his st udents atthe University of California, Berkeley; and Dana Aswad,Shiou-Chuan (Sheryl) Tsai, Michael G. Cumsky, andtheir colleagues (list ed below) at the University ofCalifornia, Irvine . Many others helped us shape th is fifthedition with their comments, suggestions , and criticisms.To all of them, we are deep ly gra teful:

Richard M. Amasino, University of Wisconsin -MadisonLouise E. Anderson , Universi ty oj Illinois at ChicagoCheryl Bailey, Univ ersity ojNebraska, LincolnKenneth Balazovich, University ojMichiganThomas O. Baldwin, Unive rsity oj Arizon aVah e Bandarian, Univ ersity ofArizonaEugene Barber, University oj RochesterSebastian Y. Bedn arek, Univ ersity oj Wisconsin- Madison.Ramachandra Bhat , Lincoln UniversityJames Blankenship, Corne tt Univ ersitySandra J. Bonetti, Colorado State University, PuebloBarbara Bowman , Univ ersity oj California, BerkeleyScott D. Briggs , Purdue Unive rsityJeff Brodsky, University ojPittsburghBen Caldwell, Missouri Western State UniversityDavid Camerini, Univ ersity ofCalifornia, IrvineGuillaume Chanfreau , University oj California, Los AngelesMelanie Coccal Univ ersity ojCalifornia) IrvineJe ffrey Cohlberg, California State University, Long BeachKim D. Collins, Univ ersity ofMarylandCharles T. Dameron, Duquesne UniversityRichard S. Eisenstein , Un iversit y oj Wisconsin-MadisonGerald W. Feigenso n, Cornell UniversityRobert H. Fillingame , University of Wisconsin-MadisonBrian Fox, Unioersuu Of Wisconsin-MadisonGerald D. Frenkel, Rutgers UniversityPerry Frey, Univ ersity oj Wisconsin- MadisonDavid E. Grah am , Uruoersitu of Texas-AustinWilliam J . Grimes , University Of ArizonaMartyn Gunn, Texas A&M UniversityOlivia Hanson, University oj Central OklahomaAmy Hark,Muhlenberg CollegeShaun V. Hernandez, University OfWisconsin-MadisonPeter Hinkle , Cornell Univ ersityP. Shing Ho, Oregon Stat e UniversilyCharles G. Hoogstrat en, Afichigan State Univers ityGerwald Jogl. Brown UniversitySir Hans Kornberg, Boston Univ ersityBob Landick, University oj Wiscons in- MadisonPa trick D. Larkin, Texas A&M Un ioersuu, Corpus ChristiRyan P. Liegel, Univ ersity of Wiscons in- MadisonMaria Linder, California State Universit y, FullertonAndy C. Lawang. Texas A&M UniversityJohn Makemson, Florid a International Univ ersityJohnC. Matthews, Uniuereitu ojMt,,,iBsippi, SchoolojPharmacuBenjamin J . McFarland, Seattl e Pacific Uniuersiu)Anant Menon, Weill Cornell Medical CollegeSabeeha Merchant, Unioersi iu oj California, Los Angeles