Detailed Contents HUMAN BIOCHEMISTRY:Fat-Free mice-a snack food Each for a Particular Purpose 995 27.6 What Regulates Our Eating Behavior?972 The Common Architecture of DNA Polymerases 995 28.4 How Is DNA Replicated in Eukaryotic Cells?996 The Cell Cycle Controls the Timing of DNA Replication 996 tokinin Are short-Term regulators of Cemno998 vides Another Control Over Replicatior Consumption aryotic Cells Also Contain a Number of Different DNA Polymerases998 AMPK Mediates Man y of the Hypothalamic Rest to These Hormones 975 28.5 How Are the Ends of Chromosomes Replicated?999 27.7 Can You Really Live Longer by Eating Less?975 HUMAN BIOCHEMISTRY:Telomeres-A Timely End to Chromosomes?999 Caloric Restriction Leads to longevity 975 Mutations in the S/R2 Gene Decrease Life Span 976 28.6 How Are RNA Genomes Replicated?1001 The Enzymatic Activities of Reverse Transcriptases 1001 SIRTI Is a Key Regulator in Caloric Restriction 977 A DEEPER LOOK RNA as Genetic Material 1001 AegSmcmy9dnRadWne6aPomt Activator of rtin 28.7 How Is the Genetic Information Rearranged by Genetic Recombination?1002 SUMMARY 978 FOUNDATIONAL BIOCHEMISTRY 980 ensT0iconRaquhes8ieabagandRaunonof PROBLEMS 981 FURTHER READING 983 lohe8Py8ar0gnPocetsAcaordns The Enzymes of General Recombination Include Reca PART IV INFORMATION TRANSFER RecBCD,RuvA,RuvB,and RuvC 1005 CBCD 2y Complex vinds dsDNA 28 DNA Metabolism:Replication,Recombination, SsDNA and Then Interact with and Repair 985 DNA Metabolism 985 28.1 IsDNA Replic on Proc rectional9 n.and NA Helix 986 Repair 1009 cal Evidence for Semidisc A DEEPER LOO Knock "Mice:A Metho tinuous DNA Replication 988 ts DNA Initiation of DNA Replication 988 Replication at Stalled Replication Forks 1010 28.2 What Are the Functions of DNA Poly rases?989 Biochemical characterization of DNA po E.colCells Have Several Different DNA Polymerases 990 E coli DNA Polymerase lll Holoenzyme Replicates the E.coli Chromosome 990 Hoyme its at Each DNA Pob I Removes the RNA Prim s and Fills 28.8 Can DNA Be Repaired?1012 in the Gaps 993 A DEEPER LOOK Pegghets8ataemoa gme rects Erors Introduced During DNA Replication 1016 NA R Factories 994 28.9 What Is the Molecular Basis of Mutation?1017 A DEEPER LOOK:A Mechanism for All Polymerases 994 Point Mutations Arise by Inappropriate Base-Pairing 1018
Detailed Contents xxiii Human Biochemistry: Fat-Free Mice—A Snack Food for Pampered Pets? No, A Model for One Form of Diabetes 970 27.6 What Regulates Our Eating Behavior? 972 The Hormones That Control Eating Behavior Come from Many Different Tissues 972 Ghrelin and Cholecystokinin Are Short-Term Regulators of Eating Behavior 973 Human Biochemistry: The Metabolic Effects of Alcohol Consumption 974 Insulin and Leptin Are Long-Term Regulators of Eating Behavior 974 AMPK Mediates Many of the Hypothalamic Responses to These Hormones 975 27.7 Can You Really Live Longer by Eating Less? 975 Caloric Restriction Leads to Longevity 975 Mutations in the SIR2 Gene Decrease Life Span 976 SIRT1 Is a Key Regulator in Caloric Restriction 977 Resveratrol, a Compound Found in Red Wine, Is a Potent Activator of Sirtuin Activity 977 SUMMARY 978 Foundational Biochemistry 980 PROBLEMS 981 Further Reading 983 Part IV Information Transfer 28 DNA Metabolism: Replication, Recombination, and Repair 985 DNA Metabolism 985 28.1 How Is DNA Replicated? 986 DNA Replication Is Bidirectional 986 Replication Requires Unwinding of the DNA Helix 986 DNA Replication Is Semidiscontinuous 987 The Biochemical Evidence for Semidiscontinuous DNA Replication 988 Initiation of DNA Replication 988 28.2 What Are the Functions of DNA Polymerases? 989 Biochemical Characterization of DNA Polymerases 989 E. coli Cells Have Several Different DNA Polymerases 990 E. coli DNA Polymerase III Holoenzyme Replicates the E. coli Chromosome 990 A DNA Polymerase III Holoenzyme Sits at Each Replication Fork 992 DNA Polymerase I Removes the RNA Primers and Fills in the Gaps 993 DNA Ligase Seals the Nicks Between Okazaki Fragments 993 DNA Polymerase Is Its Own Proofreader 993 DNA Replication Terminates at the Ter Region 993 DNA Polymerases Are Immobilized in Replication Factories 994 A Deeper Look: A Mechanism for All Polymerases 994 28.3 Why Are There So Many DNA Polymerases? 995 Cells Have Different Versions of DNA Polymerase, Each for a Particular Purpose 995 The Common Architecture of DNA Polymerases 995 28.4 How Is DNA Replicated in Eukaryotic Cells? 996 The Cell Cycle Controls the Timing of DNA Replication 996 Proteins of the Prereplication Complex Are AAA1 ATPase Family Members 998 Geminin Provides Another Control Over Replication Initiation 998 Eukaryotic Cells Also Contain a Number of Different DNA Polymerases 998 28.5 How Are the Ends of Chromosomes Replicated? 999 Human Biochemistry: Telomeres—A Timely End to Chromosomes? 999 28.6 How Are RNA Genomes Replicated? 1001 The Enzymatic Activities of Reverse Transcriptases 1001 A Deeper Look: RNA as Genetic Material 1001 28.7 How Is the Genetic Information Rearranged by Genetic Recombination? 1002 General Recombination Requires Breakage and Reunion of DNA Strands 1002 Homologous Recombination Proceeds According to the Holliday Model 1003 The Enzymes of General Recombination Include RecA, RecBCD, RuvA, RuvB, and RuvC 1005 The RecBCD Enzyme Complex Unwinds dsDNA and Cleaves Its Single Strands 1005 The RecA Protein Can Bind ssDNA and Then Interact with Duplex DNA 1006 RuvA, RuvB, and RuvC Proteins Resolve the Holliday Junction to Form the Recombination Products 1008 A Deeper Look: The Three Rs of Genomic Manipulation: Replication, Recombination, and Repair 1009 A Deeper Look: “Knockout” Mice: A Method to Investigate the Essentiality of a Gene 1009 Recombination-Dependent Replication Restarts DNA Replication at Stalled Replication Forks 1010 Homologous Recombination in Eukaryotes Helps to Prevent Cancer 1010 Human Biochemistry: The Breast Cancer Susceptibility Genes BRCA1 and BRCA2 Are Involved in DNA Damage Control and DNA Repair 1010 Transposons Are DNA Sequences That Can Move from Place to Place in the Genome 1011 28.8 Can DNA Be Repaired? 1012 A Deeper Look: Transgenic Animals Are Animals Carrying Foreign Genes 1015 Mismatch Repair Corrects Errors Introduced During DNA Replication 1016 Damage to DNA by UV Light or Chemical Modification Can Also Be Repaired 1016 28.9 What Is the Molecular Basis of Mutation? 1017 Point Mutations Arise by Inappropriate Base-Pairing 1018 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 eactosndpreeniponteactions utagens React v with the Bases in DNA 101 Insertions and Deletions 101 p Protein:Protein Contacts with RNA Polymerase 1052 Special Focus:Gene Rea ments to Response e Are Cap 29.3 How Are Genes Transcribed in Eukaryotes?1053 of Gene Rearrangement 1021 Eukaryotes Have Three Classes of RNA Polymerases 1054 RNA Polymerase ll Transcribes Protein- oding Genes 1054 The ore Comple Gene Regulatory Sequences in Eukaryotes Include DNA Rearrangements assemble an lchain gene Promoters,Enhancers,and Response Elements 1057 by Combining Three Separate Genes 1023 DNA Rearrangements Assemble an H-Chain Gene nTranscription Activatior 。 -Chain Gene and Repression 1060 Mediator as a Repressor of Transcription 1062 ifying Enzyn N y Div Ch. tin R SUMMARY 1028 Stimulated Multisubunit ATPases 1062 FOUNDATIONAL BIOCHEMISTRY 1029 Covalent Modification of Histones 1063 PROBL FURTHER READING 103 hylation and Phosphorylation Act as a Binary Switch in 29 Transcription and the Regulation of Gene the Histone Code 1064 Expression 1035 291 How Are Genes Transcribed in Bacteria?035 Features ir Eukaryotic Gene Activation 1065 Bacterial RNA Polymerases Use Their Sigma Subunits to A SINE of the Times 1066 Identify Sites s Where Transcription Be egins 1036 29.4 How Do Gene Regulatory Proteins Recognize Specific Process Transcription Has Four Stages 1036 DNA Sequences?1066 HUMAN BIOCHEMISTRY:Storage of Lon 29.2 How Is Transcription Regulated in Bacteria?1042 Transcription of O Turn-Helix Motif Use One Heli lac Operon Serves as a Paradigm of Operons 1043 or isa Negative Regula eron 104 oteins Bind to dNA via zn-Finge of the lac Op Motifs 1068 saPositive Regulator of 104 Some DNA-Bindin Zipper (bZIP)Motif 1069 ative and Positive Control Systems Are Fundamentally eins Provide the DNA-Bindine Motif 1070 29.5 How Are Fuka eRNegae2gtoTtRgco-epeso Delivered to the Ribosomesfor Translation?1070 Eukaryotic Genes Are split Genes 1070 wpa服
xxiv Detailed Contents Mutations Can Be Induced by Base Analogs 1018 Chemical Mutagens React with the Bases in DNA 1019 Insertions and Deletions 1019 Special Focus: Gene Rearrangements and Immunology—Is It Possible to Generate Protein Diversity Using Genetic Recombination? 1021 Cells Active in the Immune Response Are Capable of Gene Rearrangement 1021 Immunoglobulin G Molecules Contain Regions of Variable Amino Acid Sequence 1021 The Immunoglobulin Genes Undergo Gene Rearrangement 1022 DNA Rearrangements Assemble an L-Chain Gene by Combining Three Separate Genes 1023 DNA Rearrangements Assemble an H-Chain Gene by Combining Four Separate Genes 1024 V–J and V–D–J Joining in Light- and Heavy-Chain Gene Assembly Is Mediated by the RAG Proteins 1025 Imprecise Joining of Immunoglobulin Genes Creates New Coding Arrangements 1025 Antibody Diversity Is Due to Immunoglobulin Gene Rearrangements 1026 SUMMARY 1028 Foundational Biochemistry 1029 PROBLEMS 1030 Further Reading 1031 29 Transcription and the Regulation of Gene Expression 1035 29.1 How Are Genes Transcribed in Bacteria? 1035 A Deeper Look: Conventions Used in Expressing the Sequences of Nucleic Acids and Proteins 1036 Bacterial RNA Polymerases Use Their Sigma Subunits to Identify Sites Where Transcription Begins 1036 The Process of Transcription Has Four Stages 1036 A Deeper Look: DNA Footprinting—Identifying the Nucleotide Sequence in DNA Where a Protein Binds 1040 29.2 How Is Transcription Regulated in Bacteria? 1042 Transcription of Operons Is Controlled by Induction and Repression 1043 The lac Operon Serves as a Paradigm of Operons 1043 lac Repressor Is a Negative Regulator of the lac Operon 1044 CAP Is a Positive Regulator of the lac Operon 1046 A Deeper Look: Quantitative Evaluation of lac Repressor;DNA Interactions 1046 Negative and Positive Control Systems Are Fundamentally Different 1047 The araBAD Operon Is Both Positively and Negatively Controlled by AraC 1047 The trp Operon Is Regulated Through a Co-Repressor– Mediated Negative Control Circuit 1049 Attenuation Is a Prokaryotic Mechanism for PostTranscriptional Regulation of Gene Expression 1049 DNA;Protein Interactions and Protein;Protein Interactions Are Essential to Transcription Regulation 1051 Proteins That Activate Transcription Work Through Protein;Protein Contacts with RNA Polymerase 1052 DNA Looping Allows Multiple DNA-Binding Proteins to Interact with One Another 1053 29.3 How Are Genes Transcribed in Eukaryotes? 1053 Eukaryotes Have Three Classes of RNA Polymerases 1054 RNA Polymerase II Transcribes Protein-Coding Genes 1054 The Regulation of Gene Expression Is More Complex in Eukaryotes 1056 Gene Regulatory Sequences in Eukaryotes Include Promoters, Enhancers, and Response Elements 1057 Transcription Initiation by RNA Polymerase II Requires TBP and the GTFs 1059 The Role of Mediator in Transcription Activation and Repression 1060 Mediator as a Repressor of Transcription 1062 Chromatin-Remodeling Complexes and HistoneModifying Enzymes Alleviate the Repression Due to Nucleosomes 1062 Chromatin-Remodeling Complexes Are Nucleic Acid– Stimulated Multisubunit ATPases 1062 Covalent Modification of Histones 1063 Covalent Modification of Histones Forms the Basis of the Histone Code 1064 Methylation and Phosphorylation Act as a Binary Switch in the Histone Code 1064 Chromatin Deacetylation Leads to Transcription Repression 1065 Nucleosome Alteration and Interaction of RNA Polymerase II with the Promoter Are Essential Features in Eukaryotic Gene Activation 1065 A SINE of the Times 1066 29.4 How Do Gene Regulatory Proteins Recognize Specific DNA Sequences? 1066 Human Biochemistry: Storage of Long-Term Memory Depends on Gene Expression Activated by CREB-Type Transcription Factors 1067 a-Helices Fit Snugly into the Major Groove of B-DNA 1067 Proteins with the Helix-Turn-Helix Motif Use One Helix to Recognize DNA 1067 Some Proteins Bind to DNA via Zn-Finger Motifs 1068 Some DNA-Binding Proteins Use a Basic Region-Leucine Zipper (bZIP) Motif 1069 The Zipper Motif of bZIP Proteins Operates Through Intersubunit Interaction of Leucine Side Chains 1069 The Basic Region of bZIP Proteins Provides the DNA-Binding Motif 1070 29.5 How Are Eukaryotic Transcripts Processed and Delivered to the Ribosomes for Translation? 1070 Eukaryotic Genes Are Split Genes 1070 The Organization of Exons and Introns in Split Genes Is Both Diverse and Conserved 1071 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 0 30.4 What Is the Structure of Ribosomes,and How Are They Assembled>1101 heeseonPocedsvaFormaionofalanl Splicing depends on snRNPs 1074 usly Self.Asse le In vitro 1103 snRNPs Form the Spliceosome 1076 110d Alternative RNA Splicing Creates Protein Isoforms 1076 ryotes Are Larger Than Prokaryotic Ribosomes 1104 30.5 What Are the Mechanics of mRNA Translation?1105 Peptide Chain Initiation in Bac RNA Editing:Another Mechanism That Increases the Diversity of Genomic Information 1078 29.6 Can Gene Expression Be Regulated Once The floneation Cycle 1108 the Transcript Has Been Synthesized?1079 Aminoacyl-tRNA Binding 1109 CTP Hydrolysis Fuels the Conformational Changes That Drive Ribosomal Functions 1113 297 Can We p tures D nation Requires Yet Another g.Protei Family Member 1114 TIONAL BIOCHEMISTRY 1084 and a Pool of Free FURTHER READING 1086 30 Protein Synthesis 1091 mes Are the Active Structures of Protein 301 Synthesis 1117 de1092 30.6 How Are Proteins Synthesized in Eukaryotic Cells?1117 Codons Specify Amino A 1092 Peptide Chain Initiation in Eukarvotes 1117 A DEEPER LOOK:Natural a atural Variations in the Standard Genetic Code 1093 ost-Transcriptional Regulation of Gen 1120 30.2 How Is an Amino Acid Matched with Its Prope Peptide Chain RNA>1094 ASheteepet the nd Ceretic Coc AePw8GeaETrPphtheaToan ide Chai Termination Requires Just On Aminoacyl-RNA Synthetases Can Discriminate Between Inhibitors of Protein Synthesis 1122 the Various tRNAs 1096 SUMMARY 1124 chenchiacoliC NASynthetase Recognizes FOUNDATIONAL BIOCHEMISTRY 1125 PRORI EMS 1126 eAminoacyl- FURTHER READING 1127 A Sinele G:U Base Pair Defines tRNAAs 1098 Completing the Protein Life Cycle:Folding. 30.3 What Are the Rules in Codon-Anticodon Pairine>1099 Processing,and Degradation 1131 31.1 How Do Newly Synthesized Proteins Fold?1132 Francis Crick Proposed the"Wobble"Hypothesis for Codon-Anticod nng 109 HUMAN BIOCHEMISTRY:Alzheimer's,Parkinson's, Late ome Cod ons Are Used More Than Others 1099 ion's D。 the Accumulation of protein deposits 1133 Chaperones Help Some Proteins Fold 1134
Detailed Contents xxv Post-Transcriptional Processing of Messenger RNA Precursors Involves Capping, Methylation, Polyadenylylation, and Splicing 1072 Nuclear Pre-mRNA Splicing 1073 The Splicing Reaction Proceeds via Formation of a Lariat Intermediate 1074 Splicing Depends on snRNPs 1074 snRNPs Form the Spliceosome 1076 Alternative RNA Splicing Creates Protein Isoforms 1076 Fast Skeletal Muscle Troponin T Isoforms Are an Example of Alternative Splicing 1076 A Deeper Look: Inteins—Bizarre Parasitic Genetic Elements Encoding a Protein-Splicing Activity 1077 RNA Editing: Another Mechanism That Increases the Diversity of Genomic Information 1078 29.6 Can Gene Expression Be Regulated Once the Transcript Has Been Synthesized? 1079 miRNAs Are Key Regulators in Post-Transcriptional Gene Regulation 1079 29.7 Can We Propose a Unified Theory of Gene Expression? 1080 RNA Degradation 1082 SUMMARY 1083 Foundational Biochemistry 1084 PROBLEMS 1085 Further Reading 1086 30 Protein Synthesis 1091 30.1 What Is the Genetic Code? 1092 The Genetic Code Is a Triplet Code 1092 Codons Specify Amino Acids 1092 A Deeper Look: Natural and Unnatural Variations in the Standard Genetic Code 1093 30.2 How Is an Amino Acid Matched with Its Proper tRNA? 1094 Aminoacyl-tRNA Synthetases Interpret the Second Genetic Code 1094 Evolution Has Provided Two Distinct Classes of Aminoacyl-tRNA Synthetases 1096 Aminoacyl-tRNA Synthetases Can Discriminate Between the Various tRNAs 1096 Escherichia coli Glutaminyl-tRNAGln Synthetase Recognizes Specific Sites on tRNAGln 1098 The Identity Elements Recognized by Some AminoacyltRNA Synthetases Reside in the Anticodon 1098 A Single G;U Base Pair Defines tRNAAlas 1098 30.3 What Are the Rules in Codon–Anticodon Pairing? 1099 Francis Crick Proposed the “Wobble” Hypothesis for Codon–Anticodon Pairing 1099 Some Codons Are Used More Than Others 1099 Nonsense Suppression Occurs When Suppressor tRNAs Read Nonsense Codons 1101 30.4 What Is the Structure of Ribosomes, and How Are They Assembled? 1101 Prokaryotic Ribosomes Are Composed of 30S and 50S Subunits 1101 Prokaryotic Ribosomes Are Made from 50 Different Proteins and Three Different RNAs 1102 Ribosomes Spontaneously Self-Assemble In Vitro 1103 Ribosomes Have a Characteristic Anatomy 1104 The Cytosolic Ribosomes of Eukaryotes Are Larger Than Prokaryotic Ribosomes 1104 30.5 What Are the Mechanics of mRNA Translation? 1105 Peptide Chain Initiation in Bacteria Requires a G-Protein Family Member 1106 Peptide Chain Elongation Requires Two G-Protein Family Members 1108 The Elongation Cycle 1108 Aminoacyl-tRNA Binding 1109 GTP Hydrolysis Fuels the Conformational Changes That Drive Ribosomal Functions 1113 A Deeper Look: Molecular Mimicry—The Structures of EF-Tu;Aminoacyl-tRNA, EF-G, and RF-3 1113 Peptide Chain Termination Requires Yet Another G-Protein Family Member 1114 The Ribosomal Subunits Cycle Between 70S Complexes and a Pool of Free Subunits 1114 A Deeper Look: Tethered Ribosomes Open New Possibilities in Synthetic Biology 1116 Polyribosomes Are the Active Structures of Protein Synthesis 1117 30.6 How Are Proteins Synthesized in Eukaryotic Cells? 1117 Peptide Chain Initiation in Eukaryotes 1117 Control of Eukaryotic Peptide Chain Initiation Is One Mechanism for Post-Transcriptional Regulation of Gene Expression 1120 Peptide Chain Elongation in Eukaryotes Resembles the Prokaryotic Process 1120 Human Biochemistry: Diphtheria Toxin ADP-Ribosylates eEF2 1121 Eukaryotic Peptide Chain Termination Requires Just One Release Factor 1121 Inhibitors of Protein Synthesis 1122 SUMMARY 1124 Foundational Biochemistry 1125 PROBLEMS 1126 Further Reading 1127 31 Completing the Protein Life Cycle: Folding, Processing, and Degradation 1131 31.1 How Do Newly Synthesized Proteins Fold? 1132 Human Biochemistry: Alzheimer’s, Parkinson’s, and Huntington’s Disease Are Late-Onset Neurodegenerative Disorders Caused by the Accumulation of Protein Deposits 1133 Chaperones Help Some Proteins Fold 1134 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 fenepoepaiadonthdrophob6rcRegons 322 What Is Signal Transduction?1163 Many Signa ingPathways Involve Enzyme Cascades 1164 A DEEPER LOOK:How Does ATP Drive Chaperone embrane Interactions Mediated Protein Folding?1135 The GroES- Complex ofE Signaling Pathways Depend on Multiple Molecular Interactions 1166 Stress-Induced Unfolding 1139 ne Proteins That Function by 32.3 How Do Signal-Transducing Re ceptors Respond to the Hormonal message?1167 The Eukaryotic Hsp9 Chaperone System Acts on Proteins of Signal Transduction Pathways 1139 Are 7.TMS itSPogeetshodkpotsinsNawres 31.2 RTKs and RGCs Are Membrane-Associated Allosteric Enzymes 1169 p6sebEa5eogSemmonform Is the Most he EGF 31.3 How Do Proteins Find Their Proper Place in s an Asy metric Tyrosine the Cell>1141 Proteins Are Delivered to the Proper Cellular Compartment by Translocation 4 ns L torAdoptsa Folded Dimeric Structure 1174 e Insulin Receptor Kinas Fukarvotic Proteins Are routed to Their prone Opens the active site 1174 Destinations by Protein Sorting and Translocation 1143 Receptor Guanyly Cyclases Mediate Effects of Natriuretic Hormones 117 31.4 Regulate Cellula es are typified by A DEEPER LOOK:Nitric Oxide,Nitrogycerin,and Alfred Nobel 1177 Proteins Targeted for Destruction Are Degraded Soluble Guanylyl Cyclases Are Receptors for Nitric Oxide 1178 by Protea 32.4 How Are Receptor Signals Transduced?1178 les 50 te the Unfolding of Proteins GPCR Signals Are Transduced by G Proteins 1178 Cyclic AMP Is a Second Messenger 1179 cAMP Activates Protein Kinase A 1180 Small Ubiquitinlike Protein Modifiers Are Post-transcrptional in ProteinQu e nsducers 1181 ors in Cance ields si ers 1182 &-一A6rQ SUMMARY 1155 FOUNDATIONAL BIOCHEMISTRY 1156 HUMAN BIC HE118 Cancer,Oncogenes,and Tumor PROBLEMS 1156 FURTHER READING 1157 Also Generate Second Messengers 1184 Calcium Is a Second Messenger 1184 32 The Reception and Transmission of Extracellular Information 1161 Calmoduin Target Proteins Possessa Basic Amphiphili 32.1 What Are Hormones?1163 Helix 1185 Steroid Hormones Act in Two Ways 1163 eamorsne5mo5nmn
xxvi Detailed Contents Hsp70 Chaperones Bind to Hydrophobic Regions of Extended Polypeptides 1134 A Deeper Look: How Does ATP Drive ChaperoneMediated Protein Folding? 1135 The GroES–GroEL Complex of E. coli Is an Hsp60 Chaperonin 1137 A Deeper Look: Chaperone Proteins That Function by Stress-Induced Unfolding 1139 The Eukaryotic Hsp90 Chaperone System Acts on Proteins of Signal Transduction Pathways 1139 A Deeper Look: Small Heat Shock Proteins: Nature’s Molecular Sponges 1140 31.2 How Are Proteins Processed Following Translation? 1141 Proteolytic Cleavage Is the Most Common Form of Post-Translational Processing 1141 31.3 How Do Proteins Find Their Proper Place in the Cell? 1141 Proteins Are Delivered to the Proper Cellular Compartment by Translocation 1142 Prokaryotic Proteins Destined for Translocation Are Synthesized as Preproteins 1142 Eukaryotic Proteins Are Routed to Their Proper Destinations by Protein Sorting and Translocation 1143 Human Biochemistry: Autophagy—How Cells Recycle Their Materials 1146 31.4 How Does Protein Degradation Regulate Cellular Levels of Specific Proteins? 1147 Eukaryotic Proteins Are Targeted for Proteasome Destruction by the Ubiquitin Pathway 1147 Proteins Targeted for Destruction Are Degraded by Proteasomes 1149 ATPase Modules Mediate the Unfolding of Proteins in the Proteasome 1150 Ubiquitination Is a General Regulatory Protein Modification 1150 Small Ubiquitinlike Protein Modifiers Are Post-transcriptional Regulators 1150 HtrA Proteases Also Function in Protein Quality Control 1152 Human Biochemistry: Proteasome Inhibitors in Cancer Chemotherapy 1154 A Deeper Look: Protein Triage—A Model for Quality Control 1155 SUMMARY 1155 Foundational Biochemistry 1156 PROBLEMS 1156 Further Reading 1157 32 The Reception and Transmission of Extracellular Information 1161 32.1 What Are Hormones? 1163 Steroid Hormones Act in Two Ways 1163 Polypeptide Hormones Share Similarities of Synthesis and Processing 1163 32.2 What Is Signal Transduction? 1163 Many Signaling Pathways Involve Enzyme Cascades 1164 Signaling Pathways Connect Membrane Interactions with Events in the Nucleus 1164 Signaling Pathways Depend on Multiple Molecular Interactions 1166 32.3 How Do Signal-Transducing Receptors Respond to the Hormonal Message? 1167 The G-Protein–Coupled Receptors Are 7-TMS Integral Membrane Proteins 1168 The Single TMS Receptors Are Guanylyl Cyclases or Tyrosine Kinases 1168 RTKs and RGCs Are Membrane-Associated Allosteric Enzymes 1169 The EGF Receptor Is Activated by Ligand-Induced Dimerization 1170 EGF Receptor Activation Forms an Asymmetric Tyrosine Kinase Dimer 1171 The Insulin Receptor Mediates Several Signaling Pathways 1172 The Insulin Receptor Adopts a Folded Dimeric Structure 1174 Autophosphorylation of the Insulin Receptor Kinase Opens the Active Site 1174 Receptor Guanylyl Cyclases Mediate Effects of Natriuretic Hormones 1174 A Symmetric Dimer Binds an Asymmetric Peptide Ligand 1176 Nonreceptor Tyrosine Kinases Are Typified by pp60src 1176 A Deeper Look: Nitric Oxide, Nitroglycerin, and Alfred Nobel 1177 Soluble Guanylyl Cyclases Are Receptors for Nitric Oxide 1178 32.4 How Are Receptor Signals Transduced? 1178 GPCR Signals Are Transduced by G Proteins 1178 Cyclic AMP Is a Second Messenger 1179 cAMP Activates Protein Kinase A 1180 Ras and Other Small GTP-Binding Proteins Are Proto-Oncogene Products 1181 G Proteins Are Universal Signal Transducers 1181 Specific Phospholipases Release Second Messengers 1182 Inositol Phospholipid Breakdown Yields Inositol-1,4, 5-Trisphosphate and Diacylglycerol 1182 Activation of Phospholipase C Is Mediated by G Proteins or by Tyrosine Kinases 1182 Human Biochemistry: Cancer, Oncogenes, and Tumor Suppressor Genes 1184 Phosphatidylcholine, Sphingomyelin, and Glycosphingolipids Also Generate Second Messengers 1184 Calcium Is a Second Messenger 1184 Intracellular Calcium-Binding Proteins Mediate the Calcium Signal 1185 Calmodulin Target Proteins Possess a Basic Amphiphilic Helix 1185 Human Biochemistry: PI Metabolism and the Pharmacology of Li 1 1185 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 32.5 How Do Efectors Convert the Signals to Actions Communication at Cholinergic Synapses Depends in the Cell 1187 upon Acetylcholine 1201 Protein Kinase A Is a Paradigm of Kinases 1187 There Are Two Classes of Acetylcholine Receptors 1201 A DEEPER LOOK:Mitogen-Ac Csame2olthoneRacporsalgndcaea Protein Kinas Is a Family of Isozymes 18 eDegrades Acetylcholine in the Synaptic Cleft 1203 01189 Protein Tyrosine Phosphatase SHP. Tyrosine Phosphatase 1190 Can Act Wthin 32.6 How Are Signaling Pathways Organized and Integrated?1190 Clutamate and Aspartate Are Excitatory Amino Acid Neurotransmitters 1204 APERniMOIe8onand5aaoanAe naling Is Modulated by RGS/GAPs 119 eads to New Signaling enancee y-Aminobutyric Acid and Glycine Are Inhibitory Neurotransmitters <0g oheBochemistyof Signals from Multiple Pathways Can Be Integrated 1195 The ca Neurotransmitters Are Derived 32.7 How Do Ne the Function s?Control from Tyrosine 1212 Various Peptides Also Act as Neurotransmitters 1212 SUMMARY 1213 Nerve Impulses Are Ca d by Neurons 1197 lon Gradients Are the Source of Electrical Potentials FOUNDATIONAL BIOCHEMISTRY 1214 n Neurons 1197 PROBLEMS 1214 Action Potentials Carry the Neural Message 1198 FURTHER READING 1216 Ihi8a5galsMediedyheowof Abbreviated Answers to Problems A-1 nicate at the Synapse 1200 Index I-1
Detailed Contents xxvii 32.5 How Do Effectors Convert the Signals to Actions in the Cell? 1187 Protein Kinase A Is a Paradigm of Kinases 1187 A Deeper Look: Mitogen-Activated Protein Kinases and Phosphorelay Systems 1188 Protein Kinase C Is a Family of Isozymes 1188 Protein Tyrosine Kinase pp60c-src Is Regulated by Phosphorylation/Dephosphorylation 1189 Protein Tyrosine Phosphatase SHP-2 Is a Nonreceptor Tyrosine Phosphatase 1190 32.6 How Are Signaling Pathways Organized and Integrated? 1190 GPCRs Can Signal Through G-Protein–Independent Pathways 1191 G-Protein Signaling Is Modulated by RGS/GAPs 1191 GPCR Desensitization Leads to New Signaling Pathways 1194 A Deeper Look: Whimsical Names for Proteins and Genes 1195 Receptor Responses Can Be Coordinated by Transactivation 1195 Signals from Multiple Pathways Can Be Integrated 1195 32.7 How Do Neurotransmission Pathways Control the Function of Sensory Systems? 1197 Nerve Impulses Are Carried by Neurons 1197 Ion Gradients Are the Source of Electrical Potentials in Neurons 1197 Action Potentials Carry the Neural Message 1198 The Action Potential Is Mediated by the Flow of Na1 and K1 Ions 1199 Neurons Communicate at the Synapse 1200 Communication at Cholinergic Synapses Depends upon Acetylcholine 1201 There Are Two Classes of Acetylcholine Receptors 1201 The Nicotinic Acetylcholine Receptor Is a Ligand-Gated Ion Channel 1202 Acetylcholinesterase Degrades Acetylcholine in the Synaptic Cleft 1203 Muscarinic Receptor Function Is Mediated by G Proteins 1203 Other Neurotransmitters Can Act Within Synaptic Junctions 1203 Glutamate and Aspartate Are Excitatory Amino Acid Neurotransmitters 1204 A Deeper Look: Tetrodotoxin and Saxitoxin Are Na1 Channel Toxins 1205 Human Biochemistry: Neurexins and Neuroligins— the Scaffolding of Learning and Memory 1206 g-Aminobutyric Acid and Glycine Are Inhibitory Neurotransmitters 1208 Human Biochemistry: The Biochemistry of Neurological Disorders 1210 The Catecholamine Neurotransmitters Are Derived from Tyrosine 1212 Various Peptides Also Act as Neurotransmitters 1212 SUMMARY 1213 Foundational Biochemistry 1214 PROBLEMS 1214 Further Reading 1216 Abbreviated Answers to Problems A-1 Index I-1 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