Contents XXV 19.10 The Evolution of Oxygenic Photosynthesis 788 Fatty Acid Synthase Receives the Acetyl and Chloroplasts Evolved from Ancient The Fatty Acid Synthase Reactions Are Repeated 836 838 and Pumps Protons to Drive ATP Synthesis 789 20 Carbohydrate Biosynthesis in ate 799 840 Plants and Bacteria e sy 20.1 Photosynthetic Carbohydrate Synthesis 799 842 800 BOX21-1 MEDICINE:Mixed-Function Oxidases, s,and 84 Synthesis of Each Triose Phe ids Aro Polyunsaturated Fatty Acids 845 Requires S .Co. phate sphat 809 848 olipids are esize 848 810 812 Regulated by Hormones Ad tes Glycerol 3-phosphate 850 Activity 86e 21.3 Biosynthesis of Membrane Phospholipids 852 ng of Photosynthetic Organisms Increase Their? o nid p 852 hClascesSapiendRuscoAedian Phos nthe sis in E.coli Employs 20.3 Biosynthesis of Starch and Sucrose Euk Anionic Phospholipids om P-Diacylglyc 855 Euk hatidylserine and ate for Sucrose Synthesi 85 ire in the Cytosol of Leaf Cells s Formation of 819 Con tes to Sucrose and an E 856 d Cl 820 Sph 857 Membranes Cellulose and Bacterial Peptidoglycan 857 cula a Membrane 21.Cholesterol,,nd Biosynthesis,Regulation,and Transport 859 82 Four Sta 20.of Carbohydrate Metabolism in 8 the Plant Cel 25 pids Are Carried on 864 825 866 826 21 Lipid Biosynthesis 833 HDL Carries Out Reverse Cholesterol Transport 21.1 Biosynthesis of Fatty Acids and Eicosanoids 833 869 Malonyl-CoA Is Formed from Acetyl-CoA and 871 hesis Proceeds in a Repeating BOX21-3 MEDICINE:The Lipid Hypothesis and the Development of Statins Acid Synthase Has Multiple active sites 873
19.10 The Evolution of Oxygenic Photosynthesis 788 Chloroplasts Evolved from Ancient Photosynthetic Bacteria 788 In Halobacterium, a Single Protein Absorbs Light and Pumps Protons to Drive ATP Synthesis 789 20 Carbohydrate Biosynthesis in Plants and Bacteria 799 20.1 Photosynthetic Carbohydrate Synthesis 799 Plastids Are Organelles Unique to Plant Cells and Algae 800 Carbon Dioxide Assimilation Occurs in Three Stages 801 Synthesis of Each Triose Phosphate from CO2 Requires Six NADPH and Nine ATP 808 A Transport System Exports Triose Phosphates from the Chloroplast and Imports Phosphate 809 Four Enzymes of the Calvin Cycle Are Indirectly Activated by Light 810 20.2 Photorespiration and the C4 and CAM Pathways 812 Photorespiration Results from Rubisco’s Oxygenase Activity 812 The Salvage of Phosphoglycolate Is Costly 813 In C4 Plants, CO2 Fixation and Rubisco Activity Are Spatially Separated 815 BOX 20–1 Will Genetic Engineering of Photosynthetic Organisms Increase Their Efficiency? 816 In CAM Plants, CO2 Capture and Rubisco Action Are Temporally Separated 818 20.3 Biosynthesis of Starch and Sucrose 818 ADP-Glucose Is the Substrate for Starch Synthesis in Plant Plastids and for Glycogen Synthesis in Bacteria 818 UDP-Glucose Is the Substrate for Sucrose Synthesis in the Cytosol of Leaf Cells 819 Conversion of Triose Phosphates to Sucrose and Starch Is Tightly Regulated 820 20.4 Synthesis of Cell Wall Polysaccharides: Plant Cellulose and Bacterial Peptidoglycan 821 Cellulose Is Synthesized by Supramolecular Structures in the Plasma Membrane 822 Lipid-Linked Oligosaccharides Are Precursors for Bacterial Cell Wall Synthesis 823 20.5 Integration of Carbohydrate Metabolism in the Plant Cell 825 Gluconeogenesis Converts Fats and Proteins to Glucose in Germinating Seeds 825 Pools of Common Intermediates Link Pathways in Different Organelles 826 21 Lipid Biosynthesis 833 21.1 Biosynthesis of Fatty Acids and Eicosanoids 833 Malonyl-CoA Is Formed from Acetyl-CoA and Bicarbonate 833 Fatty Acid Synthesis Proceeds in a Repeating Reaction Sequence 834 The Mammalian Fatty Acid Synthase Has Multiple Active Sites 834 Fatty Acid Synthase Receives the Acetyl and Malonyl Groups 836 The Fatty Acid Synthase Reactions Are Repeated to Form Palmitate 838 Fatty Acid Synthesis Occurs in the Cytosol of Many Organisms but in the Chloroplasts of Plants 839 Acetate Is Shuttled out of Mitochondria as Citrate 840 Fatty Acid Biosynthesis Is Tightly Regulated 840 Long-Chain Saturated Fatty Acids Are Synthesized from Palmitate 842 Desaturation of Fatty Acids Requires a Mixed-Function Oxidase 842 BOX 21–1 MEDICINE: Mixed-Function Oxidases, Cytochrome P-450 Enzymes, and Drug Overdoses 844 Eicosanoids Are Formed from 20-Carbon Polyunsaturated Fatty Acids 845 21.2 Biosynthesis of Triacylglycerols 848 Triacylglycerols and Glycerophospholipids Are Synthesized from the Same Precursors 848 Triacylglycerol Biosynthesis in Animals Is Regulated by Hormones 849 Adipose Tissue Generates Glycerol 3-phosphate by Glyceroneogenesis 850 Thiazolidinediones Treat Type 2 Diabetes by Increasing Glyceroneogenesis 852 21.3 Biosynthesis of Membrane Phospholipids 852 Cells Have Two Strategies for Attaching Phospholipid Head Groups 852 Phospholipid Synthesis in E. coli Employs CDP-Diacylglycerol 853 Eukaryotes Synthesize Anionic Phospholipids from CDP-Diacylglycerol 855 Eukaryotic Pathways to Phosphatidylserine, Phosphatidylethanolamine, and Phosphatidylcholine Are Interrelated 855 Plasmalogen Synthesis Requires Formation of an Ether-Linked Fatty Alcohol 856 Sphingolipid and Glycerophospholipid Synthesis Share Precursors and Some Mechanisms 857 Polar Lipids Are Targeted to Specific Cellular Membranes 857 21.4 Cholesterol, Steroids, and Isoprenoids: Biosynthesis, Regulation, and Transport 859 Cholesterol Is Made from Acetyl-CoA in Four Stages 860 Cholesterol Has Several Fates 864 Cholesterol and Other Lipids Are Carried on Plasma Lipoproteins 864 BOX 21–2 MEDICINE: ApoE Alleles Predict Incidence of Alzheimer Disease 866 Cholesteryl Esters Enter Cells by ReceptorMediated Endocytosis 868 HDL Carries Out Reverse Cholesterol Transport 869 Cholesterol Synthesis and Transport Is Regulated at Several Levels 869 Dysregulation of Cholesterol Metabolism Can Lead to Cardiovascular Disease 871 BOX 21–3 MEDICINE: The Lipid Hypothesis and the Development of Statins 872 Reverse Cholesterol Transport by HDL Counters Plaque Formation and Atherosclerosis 873 Contents xxv FMTOC.indd Page xxv 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
xxvi Contents 874 920 es in Cho rimidine Bases Are Recycled by 874 22 Biosunthesis of Amino Acids. Nucleotides,and Related Molecules 881 g2 22.1 Overview of Nitrogen Metabolism 881 Hormonal Regulation and Integration of Mammalian metabolism 929 82 Nitrogen Is Fixed by Enzymes of the Nitrogenase 23.1 Hormones:Diverse Structures for Diverse Functions 929 930 BOX 23-1 MEDICINE:How sa Hormone Discovered? he Ard 931 Me Hor Cellular Receptors .Acids 891 none Release Is Regul Neuronal and Hormonal Signals 23.2 Tissue-Specific Metabolism:The Division of Labor 939 ysteine Are Derived fron 895 of Tryptophan,P 898 iagnosticAidsand the Musce Builders Friends sUses Precursors of Purine The 898 948 Blood Carries Oxygen,Metabolites,and Hormones g49 899 23.3 Hormonal Regulation of Fuel metabolism 951 951 22.3 Molecules Derived from Amino Acids % 0 BOX22-2 MEDICINE:On Kings and Vampires fncagonContesomBlodGt Am of Creatine and Brain cteria e958 sfrom Defects in Insulin 959 23.Obesity and the Regulation of Body Mass 960 909 22.4 Biosynthesis and Degradation of Nucleotides 910 aling Cascade That Regulate De Novo Purine Nucleotide Synthesis 962 912 The L tide bi synthesis Is Regulated by from Aspartate. 915 Adiponectin Acts th ough AMPK to Increase 964 ck Inhibition 916 mTORCI Activity C rdinates Cell Growth with Are Converted to 916 Diet Regu 965 the Exr of enes Central to the Precursors of 965 90 Sh or Is Influenced by 966
Steroid Hormones Are Formed by Side-Chain Cleavage and Oxidation of Cholesterol 874 Intermediates in Cholesterol Biosynthesis Have Many Alternative Fates 874 22 Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 881 22.1 Overview of Nitrogen Metabolism 881 The Nitrogen Cycle Maintains a Pool of Biologically Available Nitrogen 882 Nitrogen Is Fixed by Enzymes of the Nitrogenase Complex 882 BOX 22–1 Unusual Lifestyles of the Obscure but Abundant 884 Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine 888 Glutamine Synthetase Is a Primary Regulatory Point in Nitrogen Metabolism 889 Several Classes of Reactions Play Special Roles in the Biosynthesis of Amino Acids and Nucleotides 890 22.2 Biosynthesis of Amino Acids 891 -Ketoglutarate Gives Rise to Glutamate, Glutamine, Proline, and Arginine 892 Serine, Glycine, and Cysteine Are Derived from 3-Phosphoglycerate 892 Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruvate 895 Chorismate Is a Key Intermediate in the Synthesis of Tryptophan, Phenylalanine, and Tyrosine 898 Histidine Biosynthesis Uses Precursors of Purine Biosynthesis 898 Amino Acid Biosynthesis Is under Allosteric Regulation 899 22.3 Molecules Derived from Amino Acids 902 Glycine Is a Precursor of Porphyrins 902 Heme Is the Source of Bile Pigments 904 BOX 22–2 MEDICINE: On Kings and Vampires 906 Amino Acids Are Precursors of Creatine and Glutathione 906 D-Amino Acids Are Found Primarily in Bacteria 907 Aromatic Amino Acids Are Precursors of Many Plant Substances 908 Biological Amines Are Products of Amino Acid Decarboxylation 908 Arginine Is the Precursor for Biological Synthesis of Nitric Oxide 909 22.4 Biosynthesis and Degradation of Nucleotides 910 De Novo Purine Nucleotide Synthesis Begins with PRPP 912 Purine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition 914 Pyrimidine Nucleotides Are Made from Aspartate, PRPP, and Carbamoyl Phosphate 915 Pyrimidine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition 916 Nucleoside Monophosphates Are Converted to Nucleoside Triphosphates 916 Ribonucleotides Are the Precursors of Deoxyribonucleotides 917 Thymidylate Is Derived from dCDP and dUMP 920 Degradation of Purines and Pyrimidines Produces Uric Acid and Urea, Respectively 920 Purine and Pyrimidine Bases Are Recycled by Salvage Pathways 922 Excess Uric Acid Causes Gout 922 Many Chemotherapeutic Agents Target Enzymes in the Nucleotide Biosynthetic Pathways 923 23 Hormonal Regulation and Integration of Mammalian Metabolism 929 23.1 Hormones: Diverse Structures for Diverse Functions 929 The Detection and Purification of Hormones Requires a Bioassay 930 BOX 23–1 MEDICINE: How Is a Hormone Discovered? The Arduous Path to Purified Insulin 931 Hormones Act through Specific High-Affinity Cellular Receptors 932 Hormones Are Chemically Diverse 933 Hormone Release Is Regulated by a Hierarchy of Neuronal and Hormonal Signals 936 23.2 Tissue-Specific Metabolism: The Division of Labor 939 The Liver Processes and Distributes Nutrients 939 Adipose Tissues Store and Supply Fatty Acids 943 Brown Adipose Tissue Is Thermogenic 944 Muscles Use ATP for Mechanical Work 944 BOX 23–2 Creatine and Creatine Kinase: Invaluable Diagnostic Aids and the Muscle Builder’s Friends 946 The Brain Uses Energy for Transmission of Electrical Impulses 948 Blood Carries Oxygen, Metabolites, and Hormones 949 23.3 Hormonal Regulation of Fuel Metabolism 951 Insulin Counters High Blood Glucose 951 Pancreatic Cells Secrete Insulin in Response to Changes in Blood Glucose 953 Glucagon Counters Low Blood Glucose 955 During Fasting and Starvation, Metabolism Shifts to Provide Fuel for the Brain 956 Epinephrine Signals Impending Activity 958 Cortisol Signals Stress, Including Low Blood Glucose 958 Diabetes Mellitus Arises from Defects in Insulin Production or Action 959 23.4 Obesity and the Regulation of Body Mass 960 Adipose Tissue Has Important Endocrine Functions 960 Leptin Stimulates Production of Anorexigenic Peptide Hormones 962 Leptin Triggers a Signaling Cascade That Regulates Gene Expression 962 The Leptin System May Have Evolved to Regulate the Starvation Response 963 Insulin Acts in the Arcuate Nucleus to Regulate Eating and Energy Conservation 963 Adiponectin Acts through AMPK to Increase Insulin Sensitivity 964 mTORC1 Activity Coordinates Cell Growth with the Supply of Nutrients and Energy 965 Diet Regulates the Expression of Genes Central to Maintaining Body Mass 965 Short-Term Eating Behavior Is Influenced by Ghrelin and PYY3–36 966 xxvi Contents FMTOC.indd Page xxvi 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
Contents xxvii Nn。egy 25.2 DNA Repair 1027 23.5 Obesity,the Metabolic Syndrome,and Type 2 The Int ction Diabetes 968 n Type 2Diabetes the Tissues Becomeive DNA Synthesi Type 2Diabetes Is Managed with Diet,Exercise. BOX 25-1 MEDICINE:DNA Repair and Cancer 970 25.3 DNA Recombination 1038 Ractorial Homolog s Recombination Is a DNA 103 III INFORMATION PATHWAYS 977 24 Genes and Chromosomes 979 ciaiondrimgMeiosislslnitiatedwmth 104 24.1 Chromosomal Elements 979 1048 Code for B02-2e2 Proner Chromasomal 1045 DNA Mo ales Are Much Lon geThan the Site. DN Recombi tion Results in Precise 1046 Elements Move from One Very Complex Genes Assemble by Recombination 985 26 RNA Metabolism 1057 Topo 988 isomerases Catalyze Changes in the Linking 26.1 DNA-Dependent of RNA 1058 1060 990 BOX25-1 M RNA P I at Se 1061 92 Its Footprintona Promote 1062 24.3 The Structure of Chromosomes qnces Signal Termination of RNA Cells Have Three Kinds of Nucle 1063 Nndeasoeetheunhnenaloagtaiona RNA Polymerase II Requires Many Other Protein 106 996 1064 Nucle Selective Inhibition erase Undergoe 1068 1060 Struture,and Histone Variants 998 re Taneco 1070 1000 Bacterial DNA Is Also Highly Organized 1002 10 25 DNA Metabolism 1009 1075 25.1 DNA Replication 1011 A Ge ene Can Follows a Set of Fundamental Ribosomal RNAs and tRNAs Also Undergo 1075 101 1077 1018 Special-Function RNAs Undergo Several RNA o P 1081 Catalysts of Some DNA Replie tion Requires Many Enzymes and RNA ed at Different Rates 10e ylase Makes Random 1019 108 26.3 RNA-Dependent Synthesis of RNA and DNA 1085 Complex 1025 nscriptase Produces DNA from for Antiviral Therapy Provide Targets 1026 10
Microbial Symbionts in the Gut Influence Energy Metabolism and Adipogenesis 968 23.5 Obesity, the Metabolic Syndrome, and Type 2 Diabetes 968 In Type 2 Diabetes the Tissues Become Insensitive to Insulin 968 Type 2 Diabetes Is Managed with Diet, Exercise, and Medication 970 III INFORMATION PATHWAYS 977 24 Genes and Chromosomes 979 24.1 Chromosomal Elements 979 Genes Are Segments of DNA That Code for Polypeptide Chains and RNAs 979 DNA Molecules Are Much Longer Than the Cellular or Viral Packages That Contain Them 980 Eukaryotic Genes and Chromosomes Are Very Complex 984 24.2 DNA Supercoiling 985 Most Cellular DNA Is Underwound 986 DNA Underwinding Is Defined by Topological Linking Number 988 Topoisomerases Catalyze Changes in the Linking Number of DNA 989 DNA Compaction Requires a Special Form of Supercoiling 990 BOX 24–1 MEDICINE: Curing Disease by Inhibiting Topoisomerases 992 24.3 The Structure of Chromosomes 994 Chromatin Consists of DNA and Proteins 994 Histones Are Small, Basic Proteins 995 Nucleosomes Are the Fundamental Organizational Units of Chromatin 995 Nucleosomes Are Packed into Successively Higher-Order Structures 997 BOX 24–2 MEDICINE: Epigenetics, Nucleosome Structure, and Histone Variants 998 Condensed Chromosome Structures Are Maintained by SMC Proteins 1000 Bacterial DNA Is Also Highly Organized 1002 25 DNA Metabolism 1009 25.1 DNA Replication 1011 DNA Replication Follows a Set of Fundamental Rules 1011 DNA Is Degraded by Nucleases 1013 DNA Is Synthesized by DNA Polymerases 1013 Replication Is Very Accurate 1015 E. coli Has at Least Five DNA Polymerases 1016 DNA Replication Requires Many Enzymes and Protein Factors 1017 Replication of the E. coli Chromosome Proceeds in Stages 1019 Replication in Eukaryotic Cells Is Similar but More Complex 1025 Viral DNA Polymerases Provide Targets for Antiviral Therapy 1026 25.2 DNA Repair 1027 Mutations Are Linked to Cancer 1027 All Cells Have Multiple DNA Repair Systems 1028 The Interaction of Replication Forks with DNA Damage Can Lead to Error-Prone Translesion DNA Synthesis 1034 BOX 25–1 MEDICINE: DNA Repair and Cancer 1037 25.3 DNA Recombination 1038 Bacterial Homologous Recombination Is a DNA Repair Function 1039 Eukaryotic Homologous Recombination Is Required for Proper Chromosome Segregation during Meiosis 1041 Recombination during Meiosis Is Initiated with Double-Strand Breaks 1043 BOX 25–2 MEDICINE: Why Proper Chromosomal Segregation Matters 1045 Site-Specific Recombination Results in Precise DNA Rearrangements 1046 Transposable Genetic Elements Move from One Location to Another 1049 Immunoglobulin Genes Assemble by Recombination 1049 26 RNA Metabolism 1057 26.1 DNA-Dependent Synthesis of RNA 1058 RNA Is Synthesized by RNA Polymerases 1058 RNA Synthesis Begins at Promoters 1060 Transcription Is Regulated at Several Levels 1061 BOX 26–1 METHODS: RNA Polymerase Leaves Its Footprint on a Promoter 1062 Specific Sequences Signal Termination of RNA Synthesis 1063 Eukaryotic Cells Have Three Kinds of Nuclear RNA Polymerases 1064 RNA Polymerase II Requires Many Other Protein Factors for Its Activity 1064 DNA-Dependent RNA Polymerase Undergoes Selective Inhibition 1068 26.2 RNA Processing 1069 Eukaryotic mRNAs Are Capped at the 59 End 1070 Both Introns and Exons Are Transcribed from DNA into RNA 1070 RNA Catalyzes the Splicing of Introns 1070 Eukaryotic mRNAs Have a Distinctive 39 End Structure 1075 A Gene Can Give Rise to Multiple Products by Differential RNA Processing 1075 Ribosomal RNAs and tRNAs Also Undergo Processing 1077 Special-Function RNAs Undergo Several Types of Processing 1081 RNA Enzymes Are the Catalysts of Some Events in RNA Metabolism 1082 Cellular mRNAs Are Degraded at Different Rates 1084 Polynucleotide Phosphorylase Makes Random RNA-Like Polymers 1085 26.3 RNA-Dependent Synthesis of RNA and DNA 1085 Reverse Transcriptase Produces DNA from Viral RNA 1086 Some Retroviruses Cause Cancer and AIDS 1088 Contents xxvii FMTOC.indd Page xxvii 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
xxviii Contents 1088 1147 6-MEDICINE:Fighting AIDS with Imhibitors of 102 28 Regulation of Gene Expression 1155 28.1 Principles of Gene Regulation 1156 1092 1156 1157 xMETHS:The SELX Methdfor Gemerating 1092 nes Are ered and RNA Polymers with New Functions 1095 1158 BOX26-4 An Expanding RNA Universe Filled with TUF RNAs 1096 27 Protein Metabolism 1103 1160 Reg s Also Have Protein-Protein 27.1 The Genetic Code 1103 Interaction Domains 1163 e Was Cracked Using Artificial 28.2 Regulation of Gene Expression in Bacteria 1104 16 the Rule:Natural 116 mes 1108 1167 Mutation-Resistant H98 1169 TaATHeeaadRAEaig 111 vith rRNA Synthesis 1170 27.2 Protein Synthesis 1113 1171 1114 1173 28.3 Regulation of Gene Expression in Eukaryotes 1175 ral 1175 1118 Most Euka Correct Amino Ac s to Their tRNAs hetas 1122 Subject to Both Positive and Negative the Genetir Code 1124 Stage 2:A Specific Amino Acid Initiates Protein 127 1182 Pomed in the 12 118 1134 1184 Nonsense Suppression 1134 ed Polypeptide Chains ation of Gene Expression 1185 136 Takes Many Forms in Eukaryotes 1186 138 1186 27.3 Protein Targeting and Degradation 1139 opmental Potential That BOX28-1 Of Fins,Wings,Beaks,and Things Abbreviated Solutions to Problems AS-1 1143 Glossary 6-1 Bacteria Also Use Signal Sequences for Protein 1145 Cells Import Proteins by Receptor-Mediated Credits c-0 Endocytosis 1146 Index
Many Transposons, Retroviruses, and Introns May Have a Common Evolutionary Origin 1088 BOX 26–2 MEDICINE: Fighting AIDS with Inhibitors of HIV Reverse Transcriptase 1089 Telomerase Is a Specialized Reverse Transcriptase 1089 Some Viral RNAs Are Replicated by RNA-Dependent RNA Polymerase 1092 RNA Synthesis Offers Important Clues to Biochemical Evolution 1092 BOX 26–3 METHODS: The SELEX Method for Generating RNA Polymers with New Functions 1095 BOX 26–4 An Expanding RNA Universe Filled with TUF RNAs 1096 27 Protein Metabolism 1103 27.1 The Genetic Code 1103 The Genetic Code Was Cracked Using Artificial mRNA Templates 1104 BOX 27–1 Exceptions That Prove the Rule: Natural Variations in the Genetic Code 1108 Wobble Allows Some tRNAs to Recognize More than One Codon 1108 The Genetic Code Is Mutation-Resistant 1110 Translational Frameshifting and RNA Editing Affect How the Code Is Read 1111 27.2 Protein Synthesis 1113 Protein Biosynthesis Takes Place in Five Stages 1114 The Ribosome Is a Complex Supramolecular Machine 1115 BOX 27–2 From an RNA World to a Protein World 1117 Transfer RNAs Have Characteristic Structural Features 1118 Stage 1: Aminoacyl-tRNA Synthetases Attach the Correct Amino Acids to Their tRNAs 1119 Proofreading by Aminoacyl-tRNA Synthetases 1121 Interaction between an Aminoacyl-tRNA Synthetase and a tRNA: A “Second Genetic Code” 1122 BOX 27–3 Natural and Unnatural Expansion of the Genetic Code 1124 Stage 2: A Specific Amino Acid Initiates Protein Synthesis 1127 Stage 3: Peptide Bonds Are Formed in the Elongation Stage 1129 Stage 4: Termination of Polypeptide Synthesis Requires a Special Signal 1134 BOX 27–4 Induced Variation in the Genetic Code: Nonsense Suppression 1134 Stage 5: Newly Synthesized Polypeptide Chains Undergo Folding and Processing 1136 Protein Synthesis Is Inhibited by Many Antibiotics and Toxins 1138 27.3 Protein Targeting and Degradation 1139 Posttranslational Modification of Many Eukaryotic Proteins Begins in the Endoplasmic Reticulum 1140 Glycosylation Plays a Key Role in Protein Targeting 1141 Signal Sequences for Nuclear Transport Are Not Cleaved 1143 Bacteria Also Use Signal Sequences for Protein Targeting 1145 Cells Import Proteins by Receptor-Mediated Endocytosis 1146 Protein Degradation Is Mediated by Specialized Systems in All Cells 1147 28 Regulation of Gene Expression 1155 28.1 Principles of Gene Regulation 1156 RNA Polymerase Binds to DNA at Promoters 1156 Transcription Initiation Is Regulated by Proteins That Bind to or near Promoters 1157 Many Bacterial Genes Are Clustered and Regulated in Operons 1158 The lac Operon Is Subject to Negative Regulation 1159 Regulatory Proteins Have Discrete DNA-Binding Domains 1160 Regulatory Proteins Also Have Protein-Protein Interaction Domains 1163 28.2 Regulation of Gene Expression in Bacteria 1165 The lac Operon Undergoes Positive Regulation 1165 Many Genes for Amino Acid Biosynthetic Enzymes Are Regulated by Transcription Attenuation 1167 Induction of the SOS Response Requires Destruction of Repressor Proteins 1169 Synthesis of Ribosomal Proteins Is Coordinated with rRNA Synthesis 1170 The Function of Some mRNAs Is Regulated by Small RNAs in Cis or in Trans 1171 Some Genes Are Regulated by Genetic Recombination 1173 28.3 Regulation of Gene Expression in Eukaryotes 1175 Transcriptionally Active Chromatin Is Structurally Distinct from Inactive Chromatin 1175 Most Eukaryotic Promoters Are Positively Regulated 1176 DNA-Binding Activators and Coactivators Facilitate Assembly of the General Transcription Factors 1177 The Genes of Galactose Metabolism in Yeast Are Subject to Both Positive and Negative Regulation 1180 Transcription Activators Have a Modular Structure 1181 Eukaryotic Gene Expression Can Be Regulated by Intercellular and Intracellular Signals 1182 Regulation Can Result from Phosphorylation of Nuclear Transcription Factors 1184 Many Eukaryotic mRNAs Are Subject to Translational Repression 1184 Posttranscriptional Gene Silencing Is Mediated by RNA Interference 1185 RNA-Mediated Regulation of Gene Expression Takes Many Forms in Eukaryotes 1186 Development Is Controlled by Cascades of Regulatory Proteins 1186 Stem Cells Have Developmental Potential That Can Be Controlled 1191 BOX 28–1 Of Fins, Wings, Beaks, and Things 1194 Abbreviated Solutions to Problems AS-1 Glossary G-1 Credits C-0 Index I-1 xxviii Contents FMTOC.indd Page xxviii 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
The Foundations of Biochemistry 1.1 Cellular Foundations 2 1.2 Chemical Foundations 11 1.3 Physical Foundations 20 of chemical co an 1.4 Genetic Foundations 29 1.5 Evolutionary Foundations 32 molec each with its chara bout fourteen billion years ago,the universe arose unique three-dimensional structure,and its highly as a cataclysmic explosion of hot,energy-rich sub specific selection of binding partners in the cell. the Systems for extracting.transforming.and using energy from the environment (Fig.1-1b),enabling the nucleiinto the more complex elements.Atomsand mo forme Defined functions for each of an organism's rocks,planetoids,and planets.Thus were produced components and regulated interactions among over itsef and the ch nical ele them.Thi ay.Al with th but aso of microscopic intracellular structures and to extract energy from chemical compounds and,later individual chemical compounds.The interplay among from sunlight, they used to make a vast array of nating or comp ating changes in another.with the living organisms are made of stardust display ng a haracter beyond tha emistry asks n carrios out m th ult of which is biomolecules.When these molecules are isolated and examined individually they conform to all the physica cribe the nding organisms.The study of biochemistry shows how the collections of inanimate molecules that constitute living constantly adjust to these changes by adapting chemistry or their location in th govern the nonliving universe A capacity for precise self-replication and pla I-lc 1
1.1 Cellular Foundations 2 1.2 Chemical Foundations 11 1.3 Physical Foundations 20 1.4 Genetic Foundations 29 1.5 Evolutionary Foundations 32 A bout fourteen billion years ago, the universe arose as a cataclysmic explosion of hot, energy-rich subatomic particles. Within seconds, the simplest elements (hydrogen and helium) were formed. As the universe expanded and cooled, material condensed under the influence of gravity to form stars. Some stars became enormous and then exploded as supernovae, releasing the energy needed to fuse simpler atomic nuclei into the more complex elements. Atoms and molecules formed swirling masses of dust particles, and their accumulation led eventually to the formation of rocks, planetoids, and planets. Thus were produced, over billions of years, Earth itself and the chemical elements found on Earth today. About four billion years ago, life arose—simple microorganisms with the ability to extract energy from chemical compounds and, later, from sunlight, which they used to make a vast array of more complex biomolecules from the simple elements and compounds on the Earth’s surface. We and all other living organisms are made of stardust. Biochemistry asks how the remarkable properties of living organisms arise from the thousands of different biomolecules. When these molecules are isolated and examined individually, they conform to all the physical and chemical laws that describe the behavior of inanimate matter—as do all the processes occurring in living organisms. The study of biochemistry shows how the collections of inanimate molecules that constitute living organisms interact to maintain and perpetuate life animated solely by the physical and chemical laws that govern the nonliving universe. Yet organisms possess extraordinary attributes, properties that distinguish them from other collections of matter. What are these distinguishing features of living organisms? A high degree of chemical complexity and microscopic organization. Thousands of different molecules make up a cell’s intricate internal structures (Fig. 1–1a). These include very long polymers, each with its characteristic sequence of subunits, its unique three-dimensional structure, and its highly specific selection of binding partners in the cell. Systems for extracting, transforming, and using energy from the environment (Fig. 1–1b), enabling organisms to build and maintain their intricate structures and to do mechanical, chemical, osmotic, and electrical work. This counteracts the tendency of all matter to decay toward a more disordered state, to come to equilibrium with its surroundings. Defined functions for each of an organism’s components and regulated interactions among them. This is true not only of macroscopic structures, such as leaves and stems or hearts and lungs, but also of microscopic intracellular structures and individual chemical compounds. The interplay among the chemical components of a living organism is dynamic; changes in one component cause coordinating or compensating changes in another, with the whole ensemble displaying a character beyond that of its individual parts. The collection of molecules carries out a program, the end result of which is reproduction of the program and self-perpetuation of that collection of molecules—in short, life. Mechanisms for sensing and responding to alterations in their surroundings. Organisms constantly adjust to these changes by adapting their internal chemistry or their location in the environment. A capacity for precise self-replication and self-assembly (Fig. 1–1c). A single bacterial cell placed in a sterile nutrient medium can give rise to 1 The Foundations of Biochemistry 1