biochemistry SIXTH EDITION Reginald H.Garrett Charles M.Grisham University of Virginia With molecular graphic images by Michal Sabat,University of Virginia CemIngGE AustraliarMexicoSingaporeUnited Kingdom.United Stater
Reginald H. Garrett | Charles M. Grisham University of Virginia With molecular graphic images by Michal Sabat, University of Virginia biochemistry sixth edition Australia ● Brazil ● Mexico ● Singapore ● United Kingdom ● United States Copyright 2017 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.Garret Charles M Grisham and raised in Minneap 1日 d hi his Ph.D.in biology in 1968.Since that time,he has been at the B.S.in chemistry from the Illinois Institute of Technology in1969 University of Virginia,where he is currently Professor Emeritus and his Ph.D.in chemistry from the University of Minn esota in of Bi logy. 973.F lowing a pos University of Virginia.where he is Professor of Chemistry.He is genetic,and molecular biological aspects of inorganic nitrogen the author of previous editions of Biochemistry and Principlesof metabolism.His research interests focused on the pathway of Biochemistry (Cengage,Brooks/Cole),and numerous papers and filamentous fungi.His investigations con ctive transport ol sodium,po um. an etics ic udy systems approaches to the metabolic basis of nutrition-related CD-ROM and Workhe ook,a tutorial CD for students.His work diseases supported by the National Insti has ed by he National Institutes of He alth,the ar He is er ght Schol Unand pr t Bodenkultur in Vienna.Austria and served as Visiting Scholar at ociation.and the American Chemical Society.He isa Research the University of Cambridge on two separate occasions.During Caree Dev lopment Awardee of the National Institutes of in D and 19 siting S Sabatier/Toulouse inl and the of Chem of Sa Scientifique.Institute for Pharmacology and Structural Biology Diego He has taught biochemistry.introductory chemistry.and in France.He ta aught biochemistry at the University of Virginia American p: Society for Charles M.Grisham and Reginald H.Garrett iv
iv Charles M. Grisham was born and raised in Minneapolis, Minnesota, and educated at Benilde High School. He received his B.S. in chemistry from the Illinois Institute of Technology in 1969 and his Ph.D. in chemistry from the University of Minnesota in 1973. Following a postdoctoral appointment at the Institute for Cancer Research in Philadelphia, he joined the faculty of the University of Virginia, where he is Professor of Chemistry. He is the author of previous editions of Biochemistry and Principles of Biochemistry (Cengage, Brooks/Cole), and numerous papers and review articles on active transport of sodium, potassium, and calcium in mammalian systems, on protein kinase C, and on the applications of NMR and EPR spectroscopy to the study of biological systems. He has also authored Interactive Biochemistry CD-ROM and Workbook, a tutorial CD for students. His work has been supported by the National Institutes of Health, the National Science Foundation, the Muscular Dystrophy Association of America, the Research Corporation, the American Heart Association, and the American Chemical Society. He is a Research Career Development Awardee of the National Institutes of Health, and in 1983 and 1984 he was a Visiting Scientist at the Aarhus University Institute of Physiology Denmark. In 1999, he was Knapp Professor of Chemistry at the University of San Diego. He has taught biochemistry, introductory chemistry, and physical chemistry at the University of Virginia for more than 40 years. He is a member of the American Society for Biochemistry and Molecular Biology. Reginald H. Garrett was educated in the Baltimore city public schools and at the Johns Hopkins University, where he received his Ph.D. in biology in 1968. Since that time, he has been at the University of Virginia, where he is currently Professor Emeritus of Biology. He is the author of previous editions of Biochemistry, as well as Principles of Biochemistry (Cengage, Brooks/Cole), and numerous papers and review articles on the biochemical, genetic, and molecular biological aspects of inorganic nitrogen metabolism. His research interests focused on the pathway of nitrate assimilation in filamentous fungi. His investigations contributed substantially to our understanding of the enzymology, genetics, and regulation of this major pathway of biological nitrogen acquisition. More recently, he has collaborated in systems approaches to the metabolic basis of nutrition-related diseases. His research has been supported by the National Institutes of Health, the National Science Foundation, and private industry. He is a former Fulbright Scholar at the Universität für Bodenkultur in Vienna, Austria and served as Visiting Scholar at the University of Cambridge on two separate occasions. During the second, he was Thomas Jefferson Visiting Fellow in Downing College. In 2003, he was Professeur Invité at the Université Paul Sabatier/Toulouse III and the Centre National de la Recherche Scientifique, Institute for Pharmacology and Structural Biology in France. He taught biochemistry at the University of Virginia for 46 years. He is a member of the American Society for Biochemistry and Molecular Biology. Charles M. Grisham and Reginald H. Garrett Georgia Cobb Garrett About the Authors Copyright 2017 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 Molecular Components of Cells 1 The Facts of Life: Is the Logic of Biological Phenomena 1 Water:The Medium of Life 31 of Biological Systems 53 4 Amino Acids and the Peptide Bo d 79 5 Proteins:Their Primary Structure and Biological Functions 105 6 Proteins Secondary Tertiary and Quaternary Structure 147 7 Carbohydrates and the Glycoconjugates of Cell Surfaces 203 8 Lipids 245 9 Membranes and Membrane Transport 273 10 Nucleotides and Nucleic Acids 325 11 Structure of Nucleic Acids 353 12 Recombinant DNA,Cloning.Chimeric Genes.and Synthetic Biology 399 PART II Protein Dynamics 437 13 Enzymes-Kinetics and Specificity 437 14 Mechanisms of Enzyme Action 477 15 Enzyme Regulation 513 16 Molecular Motors 547 PART III Metabolism and Its Regulation 583 17 Metabolism:An Overview 583 18 Glycolysis 611 19 The Tricarboxylic Acid Cycle 643 20 Electron Transport and Oxidative Phosphorylation 679 21 Photosynthesis 719 22 Gluconeogenesis,Glycogen Metabolism,and the Pentose Phosphate Pathway 755 23 Fatty Acid Catabolism 795 24 Lipid Biosynthesis 825 25 Nitrogen Acquisition and Amino Acid Metabolism 877 26 Synthesis and Degradation of Nucleotides 927 27 Metabolic Integration and Organ Specialization 957 PART IV Information Transfer 985 28 DNA Metabolism:Replication,Recombination,and Repair 985 29 Transcription and the Regulation of Gene Expression 1035 30 Protein Synthesis 1091 31 Completing the Protein Life Cycle:Folding.Processing.and Degradation 1131 32 The Reception and Transmission of Extracellular Information 1161 Abbreviated A-1 ndex 1-1 cee
v Part I Molecular Components of Cells 1 1 The Facts of Life: Chemistry Is the Logic of Biological Phenomena 1 2 Water: The Medium of Life 31 3 Thermodynamics of Biological Systems 53 4 Amino Acids and the Peptide Bond 79 5 Proteins: Their Primary Structure and Biological Functions 105 6 Proteins: Secondary, Tertiary, and Quaternary Structure 147 7 Carbohydrates and the Glycoconjugates of Cell Surfaces 203 8 Lipids 245 9 Membranes and Membrane Transport 273 10 Nucleotides and Nucleic Acids 325 11 Structure of Nucleic Acids 353 12 Recombinant DNA, Cloning, Chimeric Genes, and Synthetic Biology 399 Part II Protein Dynamics 437 13 Enzymes—Kinetics and Specificity 437 14 Mechanisms of Enzyme Action 477 15 Enzyme Regulation 513 16 Molecular Motors 547 Part III Metabolism and Its Regulation 583 17 Metabolism: An Overview 583 18 Glycolysis 611 19 The Tricarboxylic Acid Cycle 643 20 Electron Transport and Oxidative Phosphorylation 679 21 Photosynthesis 719 22 Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate Pathway 755 23 Fatty Acid Catabolism 795 24 Lipid Biosynthesis 825 25 Nitrogen Acquisition and Amino Acid Metabolism 877 26 Synthesis and Degradation of Nucleotides 927 27 Metabolic Integration and Organ Specialization 957 Part IV Information Transfer 985 28 DNA Metabolism: Replication, Recombination, and Repair 985 29 Transcription and the Regulation of Gene Expression 1035 30 Protein Synthesis 1091 31 Completing the Protein Life Cycle: Folding, Processing, and Degradation 1131 32 The Reception and Transmission of Extracellular Information 1161 Abbreviated Answers to Problems A-1 Index I-1 Contents in Brief Copyright 2017 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 PARTI MOLECULAR COMPONENTS OF CELLS EgoaaowenswBooenTrSrte 1 The Facts of Life:Chemistry Is the Logic How Many Genes Doesa Cell Need?1 of Biological Phenomena 1 1.1 What Are the Distinctive Properties of Living The structural oreanization of Eukaryotic cells is more Systems?1 Complex Than That of Prokaryotic Cells 20 1.2 What Kinds of Molecules Are Biomolecules?4 1.6 What Are Viruses?22 Biomolecules Are Carbon Compounds 5 SUMMARY 26 13 FOUNDATIONAL BIOCHEMISTRY 27 PROBLEMS 27 Metabolites Are Used to Form the Building Blocks FURTHER READING 29 of Macromolecules 2 Water:The Medium of Life 31 21 What Are the Properties of Water?32 Water Has Unusual Properties 32 The Unit of Life is the Cell 10 Hydrogen Bonding in Water Is Key to Its Properties 32 14 The Structure of lce Is Based on H-Bond Formation 32 How Do the Properties of Biomolecules Reflect Their Fitness to the Living Condition?10 olbgcdlhecromeetsandTterBuldinglocs nt Properties of Water Derive from Its Pola omol Water Can lonize to Form H+and OH-37 2.2 What Is pH>38 ctrolytes dissociate co Weak Forces Maintain Biological Structure and Determine Biomolecular Interactions 12 ate Only Slightly in Water 40 The Henderson-Ha n Bonds Are Important in Biomolecular Presenc Titration Curves lustrate the Progressive Dissociation Through Structura of a Weak Acid 42 Phosphoric Acid Has Three Dissociable H+43 Chemedated byWek Biomolecular Rec 2.3 What Are Buffers,and What Do They Do?44 Range Metabolic Reactions 16 Serves HUMAN BIOCHEMISTRY:The Bicarbonate Buffer System 1.5 What Are of Cells of Blood Plasma 46 H
vi Critical Developments in Biochemistry: Synthetic Life 18 How Many Genes Does a Cell Need? 19 Archaea and Bacteria Have a Relatively Simple Structural Organization 20 The Structural Organization of Eukaryotic Cells Is More Complex Than That of Prokaryotic Cells 20 1.6 What Are Viruses? 22 SUMMARY 26 Foundational Biochemistry 27 PROBLEMS 27 Further Reading 29 2 Water: The Medium of Life 31 2.1 What Are the Properties of Water? 32 Water Has Unusual Properties 32 Hydrogen Bonding in Water Is Key to Its Properties 32 The Structure of Ice Is Based on H-Bond Formation 32 Molecular Interactions in Liquid Water Are Based on H Bonds 33 The Solvent Properties of Water Derive from Its Polar Nature 34 Water Can Ionize to Form H1 and OH2 37 2.2 What Is pH? 38 Strong Electrolytes Dissociate Completely in Water 39 Weak Electrolytes Are Substances That Dissociate Only Slightly in Water 40 The Henderson–Hasselbalch Equation Describes the Dissociation of a Weak Acid in the Presence of Its Conjugate Base 41 Titration Curves Illustrate the Progressive Dissociation of a Weak Acid 42 Phosphoric Acid Has Three Dissociable H1 43 2.3 What Are Buffers, and What Do They Do? 44 The Phosphate Buffer System Is a Major Intracellular Buffering System 45 The Imidazole Group of Histidine Also Serves as an Intracellular Buffering System 45 Human Biochemistry: The Bicarbonate Buffer System of Blood Plasma 46 “Good” Buffers Are Buffers Useful Within Physiological pH Ranges 47 Part I Molecular Components of Cells 1 The Facts of Life: Chemistry Is the Logic of Biological Phenomena 1 1.1 What Are the Distinctive Properties of Living Systems? 1 1.2 What Kinds of Molecules Are Biomolecules? 4 Biomolecules Are Carbon Compounds 5 1.3 What Is the Structural Organization of Complex Biomolecules? 7 Metabolites Are Used to Form the Building Blocks of Macromolecules 7 Organelles Represent a Higher Order in Biomolecular Organization 9 Membranes Are Supramolecular Assemblies That Define the Boundaries of Cells 9 The Unit of Life Is the Cell 10 1.4 How Do the Properties of Biomolecules Reflect Their Fitness to the Living Condition? 10 Biological Macromolecules and Their Building Blocks Have a “Sense” or Directionality 10 Biological Macromolecules Are Informational 10 Biomolecules Have Characteristic Three-Dimensional Architecture 12 Weak Forces Maintain Biological Structure and Determine Biomolecular Interactions 12 Van der Waals Attractive Forces Play an Important Role in Biomolecular Interactions 12 Hydrogen Bonds Are Important in Biomolecular Interactions 13 The Defining Concept of Biochemistry Is “Molecular Recognition Through Structural Complementarity” 14 Biomolecular Recognition Is Mediated by Weak Chemical Forces 15 Weak Forces Restrict Organisms to a Narrow Range of Environmental Conditions 15 Enzymes Catalyze Metabolic Reactions 16 The Time Scale of Life 17 1.5 What Are the Organization and Structure of Cells? 18 The Eukaryotic Cell Likely Emerged from an Archaeal Lineage 18 Detailed Contents Copyright 2017 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 HUMAN BIOCHEMISTRY:Blood ph and respiration 47 Standard Reduction Potentials Are Measured in Reaction 2.4 Half.Cells71 Vaes Can Be Used o Predict the Direction SUMMARY 48 FOUNDATIONAL BIOCHEMISTRY 49 in Redox Reactions 7 to Analyze Energy Changes PROBLEMS 50 The Reduction Potential Depends on Concentration 74 FURTHER READING 51 SUMMARY 74 FOUNDATIONAL BIOCHEMISTRY 75 3 Thermodynamics of Biological Systems 53 3.1 FURTHER READING 77 Reactions 54 4 Amino Acids and the Peptide Bond 79 the Structures and Properties of Amino ation,and the mino Acids Contain a Central Tetrahedral Carbor FoEeepodeas9peCteionforEaulbrium56 Atom 79 Amino Acids Can Join via Peptide Bonds 80 3.2 There Are 20 Common Amino Acids 81 Are There Other Ways to Classify Amino Acids?84 33 cfHond-Fr Amino Acids 21 and 22-and More?84 A DEEPER LOOK:Selenocysteine and Selenoproteins 84 Several Amino Acids Occur Only Rarely in Proteins 85 4.2 What Are the Acid-Base Properties of Amino 3.4 What Can Thermodynamic Parameters tell us about Acids?85 Biochemical Events?59 5 What Are the Characteristics of High-Energy Amino Acids Are Weak Polyprotic Acids 85 Biomolecules?60 ATP Is an Intermediate Energy-Shuttle Molecule 62 Acids 86 esno人u ric Acid Anhydrides Is Highly 4.3 What Reactions Do Amino Acids Undergo?89 4.4 What Are the Optical and Stereochemical Properties The Hydrolysis AG'of ATP and ADP Is Greater Than That of AMP66 of Amino Acids?89 Amino Acids Are Chiral Molecules 89 Acetyl Phosphate and 1.3.Bisphosp Chiral Molecules Are Described by the Dand (R.S) orylating Agents66 onventions 9 3.6 scentProtein TheLight Fantasi of H Jellyfish to Gene Expression9 olysis for ATP Is pH-De endent 67 4.5 What Are the Spectroscopic Properties of Amino of ATP 68 Acids?91 CTPegoaAcstheFetnegyofhdos overy of Absolute Configuration 92 Why Are Coupled Processes Important to Living Things?6 a 3.8 What Is the Daily Human Requirement for ATP?69 amino Aci Can Be Characterized by Nuclear Magnetic ADEEPER LOOK The Murchison Meteorite-Discovery of 39 Extraterrestrial Handedness 93 What Are Reduction Potentials,and How Are or Free Energy Change
Detailed Contents vii Standard Reduction Potentials Are Measured in Reaction Half-Cells 71 %o9 Values Can Be Used to Predict the Direction of Redox Reactions 72 %o9 Values Can Be Used to Analyze Energy Changes in Redox Reactions 72 The Reduction Potential Depends on Concentration 74 SUMMARY 74 Foundational Biochemistry 75 PROBLEMS 76 Further Reading 77 4 Amino Acids and the Peptide Bond 79 4.1 What Are the Structures and Properties of Amino Acids? 79 Typical Amino Acids Contain a Central Tetrahedral Carbon Atom 79 Amino Acids Can Join via Peptide Bonds 80 There Are 20 Common Amino Acids 81 Are There Other Ways to Classify Amino Acids? 84 Amino Acids 21 and 22—and More? 84 A Deeper Look: Selenocysteine and Selenoproteins 84 Several Amino Acids Occur Only Rarely in Proteins 85 4.2 What Are the Acid–Base Properties of Amino Acids? 85 Amino Acids Are Weak Polyprotic Acids 85 Critical Developments in Biochemistry: Adding New Chemistry to Proteins with Unnatural Amino Acids 86 Side Chains of Amino Acids Undergo Characteristic Ionizations 88 4.3 What Reactions Do Amino Acids Undergo? 89 4.4 What Are the Optical and Stereochemical Properties of Amino Acids? 89 Amino Acids Are Chiral Molecules 89 Chiral Molecules Are Described by the d,l and (R,S) Naming Conventions 90 Critical Developments in Biochemistry: Green Fluorescent Protein—The “Light Fantastic” from Jellyfish to Gene Expression 91 4.5 What Are the Spectroscopic Properties of Amino Acids? 91 Critical Developments in Biochemistry: Discovery of Optically Active Molecules and Determination of Absolute Configuration 92 Phenylalanine, Tyrosine, and Tryptophan Absorb Ultraviolet Light 92 Amino Acids Can Be Characterized by Nuclear Magnetic Resonance 92 A Deeper Look: The Murchison Meteorite—Discovery of Extraterrestrial Handedness 93 Critical Developments in Biochemistry: Rules for Description of Chiral Centers in the (R,S) System 94 Human Biochemistry: Blood pH and Respiration 47 2.4 What Properties of Water Give It a Unique Role in the Environment? 48 SUMMARY 48 Foundational Biochemistry 49 PROBLEMS 50 Further Reading 51 3 Thermodynamics of Biological Systems 53 3.1 What Are the Basic Concepts of Thermodynamics? 54 Three Quantities Describe the Energetics of Biochemical Reactions 54 All Reactions and Processes Follow the Laws of Thermodynamics 55 A Deeper Look: Entropy, Information, and the Importance of “Negentropy” 56 Free Energy Provides a Simple Criterion for Equilibrium 56 3.2 What Is the Effect of Concentration on Net Free Energy Changes? 57 3.3 What Is the Effect of pH on Standard-State Free Energies? 58 A Deeper Look: Comparing Standard State, Equilibrium, and Cellular Conditions 58 3.4 What Can Thermodynamic Parameters Tell Us About Biochemical Events? 59 3.5 What Are the Characteristics of High-Energy Biomolecules? 60 ATP Is an Intermediate Energy-Shuttle Molecule 62 Group Transfer Potentials Quantify the Reactivity of Functional Groups 62 The Hydrolysis of Phosphoric Acid Anhydrides Is Highly Favorable 63 The Hydrolysis DG89 of ATP and ADP Is Greater Than That of AMP 66 Acetyl Phosphate and 1,3-Bisphosphoglycerate Are Phosphoric-Carboxylic Anhydrides 66 Enol Phosphates Are Potent Phosphorylating Agents 66 3.6 What Are the Complex Equilibria Involved in ATP Hydrolysis? 67 The DG89 of Hydrolysis for ATP Is pH-Dependent 67 Metal Ions Affect the Free Energy of Hydrolysis of ATP 68 Concentration Affects the Free Energy of Hydrolysis of ATP 68 3.7 Why Are Coupled Processes Important to Living Things? 69 3.8 What Is the Daily Human Requirement for ATP? 69 A Deeper Look: ATP Changes the Keq by a Factor of 108 70 3.9 What Are Reduction Potentials, and How Are They Used to Account for Free Energy Changes in Redox Reactions? 71 Copyright 2017 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