ACKNOWLEDGMENTS Writing a popular textbook is both a challenge and an We are grateful to our colleagues throughout the world honor.Our goal is to convey to our students our enthu- who patiently answered our questions and shared their insigbsiatoecentdcdloements、 hey are espe ion ers fo ly thar ned Their mments oediately detect vagu ss and am We als thank our colleagues who supp editions.These reviewers are: ed,and simply bore with us during this arduous task. y of Arkansas,Fayetteville niversity,Long Beach &U Hat Young-Hoon An Cassidy dobson Diane hawley Wayne State University St.Cloud State University University of Oregon Richard Amasino Donald Doyle Blake Hill University of Wisconsin Georgia Institute of Technology Medical College of Wisconsin do State University nt Feske Kathr Suffolk iniuersity Armstrong Atlantic University Malone University Steven berr Patricia flatt Cristi lunnes University of Minnesota,Duluth Western Oregon University Rocky Mountain College Loren Bertocci Wilson Francisco Lori Isom Marian University Arizona State University University of Central Arkansas Gerald Frenkel Nitin Jain University y o Nevada,Las Vegas tian Unite ersity Mark Bra Glenda Gilla Xavier University of Louisiana David Bro s Gober Florida Gulf Coast University hHaanbnan Donald Burden Christina Goode Todd lohnson Middle Tennessee State University California State University.Fullerton Weber State University Nicholas Burgis Nina Goodey David Josephy Montclair State University Michael K
xiii ACKNOWLEDGMENTS Paul Adams University of Arkansas, Fayetteville Kevin Ahern Oregon State University Zulfiqar Ahmad A.T. Still University of Health Sciences Young-Hoon An Wayne State University Richard Amasino University of Wisconsin Kenneth Balazovich University of Michigan Donald Beitz Iowa State University Matthew Berezuk Azusa Pacific University Melanie Berkmen Suffolk University Steven Berry University of Minnesota, Duluth Loren Bertocci Marian University Mrinal Bhattacharjee Long Island University Elizabeth Blinstrup-Good University of Illinois Brian Bothner Montana State University Mark Braiman Syracuse University David Brown Florida Gulf Coast University Donald Burden Middle Tennessee State University Nicholas Burgis Eastern Washington University W. Malcom Byrnes Howard University College of Medicine Graham Carpenter Vanderbilt University School of Medicine John Cogan The Ohio State University Jeffrey Cohlberg California State University, Long Beach David Daleke Indiana University John DeBanzie Northeastern State University Cassidy Dobson St. Cloud State University Donald Doyle Georgia Institute of Technology Ludeman Eng Virginia Tech Caryn Evilia Idaho State University Kirsten Fertuck Northeastern University Brent Feske Armstrong Atlantic University Patricia Flatt Western Oregon University Wilson Francisco Arizona State University Gerald Frenkel Rutgers University Ronald Gary University of Nevada, Las Vegas Eric R. Gauthier Laurentian University Glenda Gillaspy Virginia Tech James Gober UCLA Christina Goode California State University, Fullerton Nina Goodey Montclair State University Eugene Grgory Virginia Tech Robert Grier Atlanta Metropolitan State College Neena Grover Colorado College Paul Hager East Carolina University Ann Hagerman Miami University Mary Hatcher-Skeers Scripps College Diane Hawley University of Oregon Blake Hill Medical College of Wisconsin Pui Ho Colorado State University Charles Hoogstraten Michigan State University Frans Huijing University of Miami Kathryn Huisinga Malone University Cristi Junnes Rocky Mountain College Lori Isom University of Central Arkansas Nitin Jain University of Tennessee Blythe Janowiak Saint Louis University Gerwald Jogl Brown University Kelly Johanson Xavier University of Louisiana Jerry Johnson University of Houston-Downtown Todd Johnson Weber State University David Josephy University of Guelph Michael Kalafatis Cleveland State University Marina Kazakevich University of Massachusetts-Dartmouth Jong Kim Alabama A&M University Writing a popular textbook is both a challenge and an honor. Our goal is to convey to our students our enthusiasm and understanding of a discipline to which we are devoted. They are our inspiration. Consequently, not a word was written or an illustration constructed without the knowledge that bright, engaged students would immediately detect vagueness and ambiguity. We also thank our colleagues who supported, advised, instructed, and simply bore with us during this arduous task. We are grateful to our colleagues throughout the world who patiently answered our questions and shared their insights into recent developments. We also especially thank those who served as reviewers for this new edition. Their thoughtful comments, suggestions, and encouragement have been of immense help to us in maintaining the excellence of the preceding editions. These reviewers are:
Pamela Osenkowski Kerry smith Loyola University,Chicago Clemson University Roger Koeppe Xiaping Pan Narashima sreerama University of Arkansas.Favetteville East Carolina University Colorado state University Dmitry Kolpashchikov Stefan Paula Wesley Stites University of Central Florida Northern Kentucky University University of Arkansas Min-Hao Kuo David Pendergrass Jon Stoltzfus Michigan State University University of Kansas Michigan State University Augustan versit Binghamton Darlen G temeab哥cafhomta.Dart Mare Tischler Caroll iwersity Greensboro University of Arizona Tanea Reed Ken Traxler Michael massiab Eastern Kentucky University Bemidii State University George Washington University Keri mcfarlane R BrianTrewyn Colorado School of Mines Northemn Kentucky University Denis Revie Vishwa Trivedi Michael Mendenhall Califoria Lutheran University Bethune Cookman University University of Kentucky Douglas Root Stephen Mills University of North Texas University of San Diege Smita Mohanty Diego State University Auburn University Xuemin Wan cordilis University of Missouri Smith College Yuqi Wang Ashikh seethy Saint Louis University Maulana Azad Medical College Rodney Weilbaecher ille State University New Dethi Southern Illinois University Brian Nichol Lisa Shamansky Kevin Williams University of Illinois,Chicago Califomia State University.San Western Kentucky University Brad Nolen rsity of the South University of Oregon Nicholas nsin-Milwaukee Wehavebeenworkingwiththepeopleat W.H.Freeman/ them.Our Macmillan colleagues have a knack for Macmillan Higher Education for many years now s have always b e out ever nagging re ho to the istry proje xiv
xiv Sung-Kun Kim Baylor University Roger Koeppe University of Arkansas, Fayetteville Dmitry Kolpashchikov University of Central Florida Min-Hao Kuo Michigan State University Isabel Larraza North Park University Mark Larson Augustana College Charles Lawrence Montana State University Pan Li State University of New York, Albany Darlene Loprete Rhodes College Greg Marks Carroll University Michael Massiah George Washington University Keri McFarlane Northern Kentucky University Michael Mendenhall University of Kentucky Stephen Mills University of San Diego Smita Mohanty Auburn University Debra Moriarity University of Alabama, Huntsville Stephen Munroe Marquette University Jeffrey Newman Lycoming College William Newton Virginia Tech Alfred Nichols Jacksonville State University Brian Nichols University of Illinois, Chicago Allen Nicholson Temple University Brad Nolen University of Oregon Pamela Osenkowski Loyola University, Chicago Xiaping Pan East Carolina University Stefan Paula Northern Kentucky University David Pendergrass University of Kansas-Edwards Wendy Pogozelski State University of New York, Geneseo Gary Powell Clemson University Geraldine Prody Western Washington University Joseph Provost University of San Diego Greg Raner University of North Carolina, Greensboro Tanea Reed Eastern Kentucky University Christopher Reid Bryant University Denis Revie California Lutheran University Douglas Root University of North Texas Johannes Rudolph University of Colorado Brian Sato University of California, Irvine Glen Sauer Fairfield University Joel Schildbach Johns Hopkins University Stylianos Scordilis Smith College Ashikh Seethy Maulana Azad Medical College, New Delhi Lisa Shamansky California State University, San Bernardino Bethel Sharma Sewanee: University of the South Nicholas Silvaggi University of Wisconsin-Milwaukee Kerry Smith Clemson University Narashima Sreerama Colorado State University Wesley Stites University of Arkansas Jon Stoltzfus Michigan State University Gerald Stubbs Vanderbilt University Takita Sumter Winthrop University Anna Tan-Wilson State University of New York, Binghamton Steven Theg University of California, Davis Marc Tischler University of Arizona Ken Traxler Bemidji State University Brian Trewyn Colorado School of Mines Vishwa Trivedi Bethune Cookman University Panayiotis Vacratsis University of Windsor Peter van der Geer San Diego State University Jeffrey Voigt Albany College of Pharmacy and Health Sciences Grover Waldrop Louisiana State University Xuemin Wang University of Missouri Yuqi Wang Saint Louis University Rodney Weilbaecher Southern Illinois University Kevin Williams Western Kentucky University Laura Zapanta University of Pittsburgh Brent Znosko Saint Louis University We have been working with the people at W. H. Freeman/ Macmillan Higher Education for many years now, and our experiences have always been enjoyable and rewarding. Writing and producing the eighth edition of Biochemistry confi rmed our belief that they are a wonderful publishing team and we are honored to work with them. Our Macmillan colleagues have a knack for undertaking stressful, but exhilarating, projects and reducing the stress without reducing the exhilaration and a remarkable ability to coax without ever nagging. We have many people to thank for this experience, some of whom are fi rst timers to the Biochemistry project
We are on Coordir ,made sure that the significant difficultie unfail: for wa scheduling.compo ac nd Dwer our de the media program.In addition,Amanda ably coordi of working with a number of outstanding developmental nated the print supplements plan.Special thanks als editors over the years,and Irene continues this tradi Shannon Molo ey and Nandin ene is thoughtful,insightful,and very efficient at Ahuja.S andy Execu e Marketing anage than cl sa Sam d nd his sale staff for tions and a eneral so Seno PrEditor Deni ShrheRedd. ort.Without their able and enthusiastic p of our text to the academic community,all of ou managed the flow of the entire project,from copyediting efforts would be in vain.We also wish to thank Kate through bound book,with admirable efficiency.Irene Ahr Parker,Publisher.for her encouragement and belie rtanott Mercy Heston,our manuscript tors in us ency and clarity of the hanks al tions as w toour many c as throug P 1 phasizing its t t.Finally.we a debt of ude to Christine buese and photo researcher lacalyn wone our wives Wendie Bere Alison Un and found the photographs that we hope make the text not Megan Williams,and our children,especially Timothy only more inviting,but also fun to look through.Janice Donnola,Ilustra Coordinator ected the undertaken,let alone successfully completed
xv We are delighted to work with Senior Acquisitions Editor, Lauren Schultz, for the fi rst time. She was unfailing in her enthusiasm and generous with her support. Another new member of the team was our developmental editor, Irene Pech. We have had the pleasure of working with a number of outstanding developmental editors over the years, and Irene continues this tradition. Irene is thoughtful, insightful, and very effi cient at identifying aspects of our writing and fi gures that were less than clear. Lisa Samols, a former developmental editor, served as a consultant, archivist for previous editions, and a general source of publishing knowledge. Senior Project Editor Deni Showers, with Sherrill Redd, managed the fl ow of the entire project, from copyediting through bound book, with admirable effi ciency. Irene Vartanoff and Mercy Heston, our manuscript editors, enhanced the literary consistency and clarity of the text. Vicki Tomaselli, Design Manager, produced a design and layout that makes the book uniquely attractive while still emphasizing its ties to past editions. Photo Editor Christine Buese and Photo Researcher Jacalyn Wong found the photographs that we hope make the text not only more inviting, but also fun to look through. Janice Donnola, Illustration Coordinator, deftly directed the rendering of new illustrations. Paul Rohloff, Production Coordinator, made sure that the signifi cant diffi culties of scheduling, composition, and manufacturing were smoothly overcome. Amanda Dunning and Donna Brodman did a wonderful job in their management of the media program. In addition, Amanda ably coordinated the print supplements plan. Special thanks also to editorial assistants Shannon Moloney and Nandini Ahuja. Sandy Lindelof, Executive Marketing Manager, enthusiastically introduced this newest edition of Biochemistry to the academic world. We are deeply appreciative of Craig Bleyer and his sales staff for their support. Without their able and enthusiastic presentation of our text to the academic community, all of our efforts would be in vain. We also wish to thank Kate Ahr Parker, Publisher, for her encouragement and belief in us. Thanks also to our many colleagues at our own institutions as well as throughout the country who patiently answered our questions and encouraged us on our quest. Finally, we owe a debt of gratitude to our families—our wives, Wendie Berg, Alison Unger, and Megan Williams, and our children, especially Timothy and Mark Gatto. Without their support, comfort, and understanding, this endeavor could never have been undertaken, let alone successfully completed
BRIEF CONTENTS CONTENTS Part I THE MOLECULAR DESIGN OF LIFE Preface 1 Biochemistry:An Evolvina Science 1 Part I THE MOLECULAR DESIGN OF LIFE 2 Protein Composition and Structure 27 3 Exploring Proteins and Proteomes 65 CHAPTER1 Biochemistry:An Evolving Science 1 4 DNA,RNA,and the Flow of Genetic Information 105 1.1 Biochemical Unity Underlies Biological Diversity 5 Exploring Genes and Genomes 135 6Exploring Evolution and Bioinformatics169 .2DNA ustrates the Interplay Between Fomm and 7 Hemoglobin:Portrait of a Protein in Action 191 DNA is const 8 Enzymes:Basic Concepts and Kinetics 215 mbine to form a double helix DNA structure explains heredity and the storage of 9 Catalytic Strategies 251 information 5 10 Regulatory Stra 285 11 Carbohydrates 315 .Chemistry Explain the Properties 12 Lipids and Cell Membranes 341 NA double helix pl 13 Membrane Channels and Pumps 367 Covalent and nt for 14 Signal-Tra ways 307 the structure and stability of biological molecules Part II TRANSDUCING AND STORING ENERGY The double helix is an expression of the rules of chemistry 15 Metabolism:Basic Concepts and Design 423 16 Glycolysis and Gluconeogenesis 449 Heat is released in the formation of the double helix 12 Acid-base reactions are central in many biochemical 17 The Citric Acid Cycle 495 18 Oxidative Phosphorylation 523 11. can dig upt 19The Light Reactions of Photosynthesis 565 nd in the lab atory 20nd h Pentose Phosphate athway 公 21 Glycogen Metabolism 617 ncing has transformed biochemistry 22 Fatty Acid Metabolism 643 23 Protein Turnover and Amino Acid Catabolism 681 nistry Part IlI SYNTHESIZING THE MOLECULES OF LIFE APPENDIX:Visualizing Molecular Structures I: 24 The Biosynthesis of Amino Acids 713 mall Molecules 25 Nucleotide Biosynthesis 743 26of Membrane pids and CHAPTER 2 Protein Composition and Structure 27 The Integration of Metabolism 801 2.1 Proteins Are Built from a Repertoire of 20 Amino 28 DNA Replication.Repair.and Recombination 827 Acids 29 29 RNA Synthesis and Processing 859 2.2 Primary Structure:Amino Acids Are Linked by 30 Protein Synthesis 893 Peptide Bonds to Form Polypeptide Chains 35 The Control of Gene Expression in Prokaryotes 925 Proteins have unique amino acid sequences specified 37 32 The Control of Gene Expression in Eukaryotes 941 tide chains are flexible yet conformationally 38 Part IV RESPONDING TO ENVIRONMENTAL CHANGES 2.3 Secondary Structure:Polypeptide Chains Can e Alpha 33 Sensory Systems 96 34 The Immune System 981 35 Molecular Motors 1011 % 36 Drug Development 1033 bonding pep
BRIEF CONTENTS Part I THE MOLECULAR DESIGN OF LIFE 1 Biochemistry: An Evolving Science 1 2 Protein Composition and Structure 27 3 Exploring Proteins and Proteomes 65 4 DNA, RNA, and the Flow of Genetic Information 105 5 Exploring Genes and Genomes 135 6 Exploring Evolution and Bioinformatics 169 7 Hemoglobin: Portrait of a Protein in Action 191 8 Enzymes: Basic Concepts and Kinetics 215 9 Catalytic Strategies 251 10 Regulatory Strategies 285 11 Carbohydrates 315 12 Lipids and Cell Membranes 341 13 Membrane Channels and Pumps 367 14 Signal-Transduction Pathways 397 Part II TRANSDUCING AND STORING ENERGY 15 Metabolism: Basic Concepts and Design 423 16 Glycolysis and Gluconeogenesis 449 17 The Citric Acid Cycle 495 18 Oxidative Phosphorylation 523 19 The Light Reactions of Photosynthesis 565 20 The Calvin Cycle and the Pentose Phosphate Pathway 589 21 Glycogen Metabolism 617 22 Fatty Acid Metabolism 643 23 Protein Turnover and Amino Acid Catabolism 681 Part III SYNTHESIZING THE MOLECULES OF LIFE 24 The Biosynthesis of Amino Acids 713 25 Nucleotide Biosynthesis 743 26 The Biosynthesis of Membrane Lipids and Steroids 767 27 The Integration of Metabolism 801 28 DNA Replication, Repair, and Recombination 827 29 RNA Synthesis and Processing 859 30 Protein Synthesis 893 31 The Control of Gene Expression in Prokaryotes 925 32 The Control of Gene Expression in Eukaryotes 941 Part IV RESPONDING TO ENVIRONMENTAL CHANGES 33 Sensory Systems 961 34 The Immune System 981 35 Molecular Motors 1011 36 Drug Development 1033 Preface v Part I THE MOLECULAR DESIGN OF LIFE 1 CHAPTER 1 Biochemistry: An Evolving Science 1 1.1 Biochemical Unity Underlies Biological Diversity 1 1.2 DNA Illustrates the Interplay Between Form and Function 4 DNA is constructed from four building blocks 4 Two single strands of DNA combine to form a double helix 5 DNA structure explains heredity and the storage of information 5 1.3 Concepts from Chemistry Explain the Properties of Biological Molecules 6 The formation of the DNA double helix as a key example 6 The double helix can form from its component strands 6 Covalent and noncovalent bonds are important for the structure and stability of biological molecules 6 The double helix is an expression of the rules of chemistry 9 The laws of thermodynamics govern the behavior of biochemical systems 10 Heat is released in the formation of the double helix 12 Acid–base reactions are central in many biochemical processes 13 Acid–base reactions can disrupt the double helix 14 Buffers regulate pH in organisms and in the laboratory 15 1.4 The Genomic Revolution Is Transforming Biochemistry, Medicine, and Other Fields 17 Genome sequencing has transformed biochemistry and other fields 17 Environmental factors influence human biochemistry 20 Genome sequences encode proteins and patterns of expression 21 APPENDIX: Visualizing Molecular Structures I: Small Molecules 22 CHAPTER 2 Protein Composition and Structure 27 2.1 Proteins Are Built from a Repertoire of 20 Amino Acids 29 2.2 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains 35 Proteins have unique amino acid sequences specified by genes 37 Polypeptide chains are flexible yet conformationally restricted 38 2.3 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops 40 The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds 40 Beta sheets are stabilized by hydrogen bonding between polypeptide strands 42 CHAPTER 1 Biochemistry: An Evolving Science 1 CHAPTER 2 Protein Composition and Structure 27 CONTENTS
Contents xvii Polypepe hains can chng direction by making revrse 3.3 Mass Spectrometry Is a Powerful Technique s provide structural support for cells ation of Peptides and Proteins es can 87 4 2.4 Tertiary Structure:Water-Soluble Proteins 88 Fold into Compact Structures with Nonpolar Cores Genomic and proteomic methods are complementary 89 2.5 Quaternary Structure:Polypeptide Chains Can Assemble into Multisubunit Structures 90 2.6 The Amino Acid Sequence of a Protein Individual proteins can be identified by mass Determines Its Three-Dimensional Structure 91 3.4 Peptides Can Be Synthesized by Automated ensities for Solid-Phase Methods 92 55 3.5 Three-Dimensional Protein Structure Can Be mediates Determined by X-ray Crystallography and NMR roscop 95 nsional structure from sequence 95 ns a grea 54 tly unstructured and can exist Nucle copy can reveal 55 capabilities CHAPTER 4 DNA,RNA,and the Flow of APPENDIX:Visualizir tructures II:Protein Genetic Information 105 CHAPTER 3 Exploring Proteins and Proteomes 65 hate Ba 106 RNA and DNA differ in the sugar component and The proteome is the functional representation of one of the bases 106 66 re the m s Is an E ssential A molecules are very l ng and have directionality 108 .2 do w n that we are 87 Double-Helical Structure 109 m the Hfinecordingtosok r Wa 19m 71 backbone phosphates zigzag 112 Some DNA molecules are circular and supercoiled 113 Single-stranded nucleic acids can adopt elaborate 113 76 vith the Accurate 114 Differences in DNA density established the validity 3.2 Immunology Provides Important Techniques with Which to Investigate Proteins rvative replication hypothesis Antibodies to specific proteins can be generated 116 with virtually any desired 4.4 DNA Is Replicated by Polymerases That Take 80 117 Proteins antified by using an catalyzes phosphodicster 117 nzym assay The genes of some viruses are made of RNA 118 83 4.5 Gene Expression Is the Transformatio rs make the visualization of proteins of DNA Infe mation into Functional Molecules 84 Several kinds of RNA play key roles in gene expression 119
Contents xvii Polypeptide chains can change direction by making reverse turns and loops 44 Fibrous proteins provide structural support for cells and tissues 44 2.4 Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores 46 2.5 Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures 48 2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure 49 Amino acids have different propensities for forming a helices, b sheets, and turns 51 Protein folding is a highly cooperative process 52 Proteins fold by progressive stabilization of intermediates rather than by random search 53 Prediction of three-dimensional structure from sequence remains a great challenge 54 Some proteins are inherently unstructured and can exist in multiple conformations 55 Protein misfolding and aggregation are associated with some neurological diseases 56 Protein modification and cleavage confer new capabilities 57 APPENDIX: Visualizing Molecular Structures II: Proteins 61 CHAPTER 3 Exploring Proteins and Proteomes 65 The proteome is the functional representation of the genome 66 3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function 66 The assay: How do we recognize the protein that we are looking for? 67 Proteins must be released from the cell to be purified 67 Proteins can be purified according to solubility, size, charge, and binding affinity 68 Proteins can be separated by gel electrophoresis and displayed 71 A protein purification scheme can be quantitatively evaluated 75 Ultracentrifugation is valuable for separating biomolecules and determining their masses 76 Protein purification can be made easier with the use of recombinant DNA technology 78 3.2 Immunology Provides Important Techniques with Which to Investigate Proteins 79 Antibodies to specific proteins can be generated 79 Monoclonal antibodies with virtually any desired specificity can be readily prepared 80 Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay 82 Western blotting permits the detection of proteins separated by gel electrophoresis 83 Fluorescent markers make the visualization of proteins in the cell possible 84 3.3 Mass Spectrometry Is a Powerful Technique for the Identification of Peptides and Proteins 85 Peptides can be sequenced by mass spectrometry 87 Proteins can be specifically cleaved into small peptides to facilitate analysis 88 Genomic and proteomic methods are complementary 89 The amino acid sequence of a protein provides valuable information 90 Individual proteins can be identified by mass spectrometry 91 3.4 Peptides Can Be Synthesized by Automated Solid-Phase Methods 92 3.5 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography and NMR Spectroscopy 95 X-ray crystallography reveals three-dimensional structure in atomic detail 95 Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution 97 CHAPTER 4 DNA, RNA, and the Flow of Genetic Information 105 4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar–Phosphate Backbone 106 RNA and DNA differ in the sugar component and one of the bases 106 Nucleotides are the monomeric units of nucleic acids 107 DNA molecules are very long and have directionality 108 4.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure 109 The double helix is stabilized by hydrogen bonds and van der Waals interactions 109 DNA can assume a variety of structural forms 111 Z-DNA is a left-handed double helix in which backbone phosphates zigzag 112 Some DNA molecules are circular and supercoiled 113 Single-stranded nucleic acids can adopt elaborate structures 113 4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information 114 Differences in DNA density established the validity of the semiconservative replication hypothesis 115 The double helix can be reversibly melted 116 4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates 117 DNA polymerase catalyzes phosphodiesterbridge formation 117 The genes of some viruses are made of RNA 118 4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules 119 Several kinds of RNA play key roles in gene expression 119 CHAPTER 3 Exploring Proteins and Proteomes 65 CHAPTER 4 DNA, RNA, and the Flow of Genetic Information 105