Detailed Contents ,0dSlPa2entheOeaPoces How Many Protons Are Required to Make an ATP? The path of Photosynthetic Electron Transfer is Called It Depends on the Organism 703 the Z Scheme 727 RackerandStoe xygen Evolution Requires the Accumulation of Four fromH,to Replace Electrons Los Ahout the Mechanism 703 0mp680729 Uncouplers Disrupt the Coupling of Electron Transport Electrons from PSll Are Transferred to PSI and ATP Synthase 705 via the Cytochrome bef Complex 729 HUMAN BIO CHEMIS ATR-ADP T ate Me the M 21.4 Architecture of osyntheti and ADP Across the Mitochondrial Membrane 706 3731 20.5 What Is the P/O Ratio for Mitochondrial Oxidative thetic Reaction Cente Phosphorylation?707 Is an Integral Membrane Protein 731 20.6 How Are the Electrons of Cytosolic NADH Fed into Electron Transport?708 ATP Synthes 708 Aspartate Shuttles Reversible9 How Does PSII Generate O,from HO?734 Dependso The Molecular Architecture of PSI Resembles the R.viridis Reaction Center and PSII Architecture 735 3.5 Billion Years of Evolution Have Resulted in a Very How Do Green Plants Carry Out Photosynthesis?736 Efficient System 711 21.5 What Is the Ouantum Yield of Photosynthesis?737 20.7 How Do Mitochondria Mediate Apoptosis?711 siog7-kgy Cytochrome c Triggers Apoptosome Assembly 711 0s73 21.6 How Does Light Drive the Synthesis of ATP?737 SUMMARY 714 ATD C FOUNDATIONAL BIOCHEMISTRY 715 s the Chloroplast Equivalent of the Mitochondrial FF-ATP Synthase73 PROBLEMS 715 on Can Occur in Either a Noncyclic FURTHER READING 717 21 Photosynthesis 719 21.1 What Are the General Pro es of Phot synthesis?720 nes 720 217 nthesis ts of Both Light Reactions and Dark Reactions 7 Ribulose-1.5-Bisp sphate ls the co acceptor R5sh52aneroaort6rhoesynheicNaoPl in CO2 Fixation 741 Caoxy-3-Keto-A Arabinitol Is an Intermediate in the 21.2 How Is Solar Energy Captured by Chlorophyll?723 p:p and Active Forms 742 te Car synthetic Pigments on Cycl of the Calvin Cycle Serve Three Metabolic The Calvin Cycle Reactions Can Account for Net Hexose Synthesis 743 What Kinds of Photosystems Are Used to Capture The Carbon Dio Pathway s by Light 7 Light En a3726 Cycle Activity 746 wn中p年飞
xviii Detailed Contents Proton Flow Through F0 Drives Rotation of the Motor and Synthesis of ATP 701 How Many Protons Are Required to Make an ATP? It Depends on the Organism 703 Racker and Stoeckenius Confirmed the Mitchell Model in a Reconstitution Experiment 703 Inhibitors of Oxidative Phosphorylation Reveal Insights About the Mechanism 703 Uncouplers Disrupt the Coupling of Electron Transport and ATP Synthase 705 Human Biochemistry: Endogenous Uncouplers— Novel Proteins with Many Beneficial Effects 705 ATP–ADP Translocase Mediates the Movement of ATP and ADP Across the Mitochondrial Membrane 706 20.5 What Is the P/O Ratio for Mitochondrial Oxidative Phosphorylation? 707 20.6 How Are the Electrons of Cytosolic NADH Fed into Electron Transport? 708 The Glycerophosphate Shuttle Ensures Efficient Use of Cytosolic NADH 708 The Malate–Aspartate Shuttle Is Reversible 709 The Net Yield of ATP from Glucose Oxidation Depends on the Shuttle Used 709 3.5 Billion Years of Evolution Have Resulted in a Very Efficient System 711 20.7 How Do Mitochondria Mediate Apoptosis? 711 Cytochrome c Triggers Apoptosome Assembly 711 Human Biochemistry: Cardiolipin—Key to Mitochondrial Physiology 713 SUMMARY 714 Foundational Biochemistry 715 PROBLEMS 715 Further Reading 717 21 Photosynthesis 719 21.1 What Are the General Properties of Photosynthesis? 720 Photosynthesis Occurs in Membranes 720 Photosynthesis Consists of Both Light Reactions and Dark Reactions 721 Water Is the Ultimate e2 Donor for Photosynthetic NADP1 Reduction 722 21.2 How Is Solar Energy Captured by Chlorophyll? 723 Chlorophylls and Accessory Light-Harvesting Pigments Absorb Light of Different Wavelengths 723 The Light Energy Absorbed by Photosynthetic Pigments Has Several Possible Fates 724 The Transduction of Light Energy into Chemical Energy Involves Oxidation–Reduction 725 Photosynthetic Units Consist of Many Chlorophyll Molecules but Only a Single Reaction Center 726 21.3 What Kinds of Photosystems Are Used to Capture Light Energy? 726 Chlorophyll Exists in Plant Membranes in Association with Proteins 727 PSI and PSII Participate in the Overall Process of Photosynthesis 727 The Pathway of Photosynthetic Electron Transfer Is Called the Z Scheme 727 Oxygen Evolution Requires the Accumulation of Four Oxidizing Equivalents in PSII 729 Electrons Are Taken from H2O to Replace Electrons Lost from P680 729 Electrons from PSII Are Transferred to PSI via the Cytochrome b6 f Complex 729 Plastocyanin Transfers Electrons from the Cytochrome b6 f Complex to PSI 730 21.4 What Is the Molecular Architecture of Photosynthetic Reaction Centers? 731 The R. viridis Photosynthetic Reaction Center Is an Integral Membrane Protein 731 Photosynthetic Electron Transfer by the R. viridis Reaction Center Leads to ATP Synthesis 731 The Molecular Architecture of PSII Resembles the R. viridis Reaction Center Architecture 732 How Does PSII Generate O2 from H2O? 734 The Molecular Architecture of PSI Resembles the R. viridis Reaction Center and PSII Architecture 735 How Do Green Plants Carry Out Photosynthesis? 736 21.5 What Is the Quantum Yield of Photosynthesis? 737 Calculation of the Photosynthetic Energy Requirements for Hexose Synthesis Depends on H1/hy and ATP/H1 Ratios 737 21.6 How Does Light Drive the Synthesis of ATP? 737 The Mechanism of Photophosphorylation Is Chemiosmotic 738 CF1CF0–ATP Synthase Is the Chloroplast Equivalent of the Mitochondrial F1F0–ATP Synthase 738 Photophosphorylation Can Occur in Either a Noncyclic or a Cyclic Mode 738 Cyclic Photophosphorylation Generates ATP but Not NADPH or O2 740 21.7 How Is Carbon Dioxide Used to Make Organic Molecules? 740 Ribulose-1,5-Bisphosphate Is the CO2 Acceptor in CO2 Fixation 741 2-Carboxy-3-Keto-Arabinitol Is an Intermediate in the Ribulose-1,5-Bisphosphate Carboxylase Reaction 741 Ribulose-1,5-Bisphosphate Carboxylase Exists in Inactive and Active Forms 742 CO2 Fixation into Carbohydrate Proceeds via the Calvin–Benson Cycle 742 The Enzymes of the Calvin Cycle Serve Three Metabolic Purposes 742 The Calvin Cycle Reactions Can Account for Net Hexose Synthesis 743 The Carbon Dioxide Fixation Pathway Is Indirectly Activated by Light 745 Protein–Protein Interactions Mediated by an Intrinsically Unstructured Protein Also Regulate Calvin–Benson Cycle Activity 746 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 xix 21.8 How Does Photorespiration Limit CO2 Fixation?746 ADEEPER LOOK Carbohydrate Utilization in Exercise 775 Tronical Crasses Use the Hatch-lack path HUMAN BIOCHEMISTRY:von Gierke Diseas to Capture Carbon Dioxide for CO Fixation746 A Glycogen-Storage Disease 776 Cacti and Other Desert Plants Capture CO at Night 749 SUMMARY 749 FOUNDATIONAL BIOCHEMISTRY 750 22.6 PRORLEMS 751 vay Operates Mainl FURTHER READING 753 The Pentose Phosphate Pathway Begins with Two 22 Gluconeogenesis,Glycogen Metabolism Oxidative Steps 780 and the Pentose Phosphate Pathway 75 ogenesis,and How Does Pathw ay 7c 22.1 What Is Gluc It Operate?755 Aldose Reductase and Diabetic enesis Include Pyruvate nds on the cell's need fo nd idn n nm rs in the Live HUMAN BIOCHEMISTRY The Chemistry of Glucose Metabolism 788 Monitoring Devices Xvlulose-5-Phosphate Is a Metabolic Regulator 789 Gluconeogenesis Is Not Me rely the Re SUMMARY 790 FOUNDATIONAL BIOCHEMISTRY 790 PRORI EMS 791 Four reactions are unique to glucon HUMAN BIOCHEMISTRY Gluconed FURTHER READING 792 and Other Diabetes Therapy Strategies 762 23 Fatty Acid Catabolism 795 22.2 How Is Gluconeogenesis Regulated?763 23.1 How Are Fats Mobilize dies of C rland Gerty Cori763 Modern Diets Are Oft n High in Fat 795 s764 PER LOOK TIGAR Substrate Cycles Provide Metabolic Control Mechanisms 767 22.3 ndc Cad -Tramp Dietary Starch Breakdown Provides Metabolic Energy767 Metabolism of Tissue Glycogen Is Regulated 769 A DEEPER LOOK:The Biochemistry of Obesity 800 22.4 How Is Glycogen Synthesized?769 23.2 How Are Fatty Acids Broken Down 800 d the Ete ntial of B-Oxidation800 aflez5ynthestsDinenbyPrynophosphate Coenzyme A Activates Fatty Acids for Degradation 80 Synthase catalyze ormation of a(1-4) Glycosidic Bonds in Glycogen 77 SggngnchingocustyTansierodTemindlcan ted Sequence of Four Reactions 803 Advanced Gly EPER LO OK A Trifu 22.5 tionalP olism Is Highly Regulated 773 e Is Regulated by Coval HUMAN BIOCHEMISTRY:Exercise Can Reverse Modification 773 the Consequence of Me D0 tic Acid Yie
Detailed Contents xix 21.8 How Does Photorespiration Limit CO2 Fixation? 746 Tropical Grasses Use the Hatch–Slack Pathway to Capture Carbon Dioxide for CO2 Fixation 746 Cacti and Other Desert Plants Capture CO2 at Night 749 SUMMARY 749 Foundational Biochemistry 750 PROBLEMS 751 Further Reading 753 22 Gluconeogenesis, Glycogen Metabolism, and the Pentose Phosphate Pathway 755 22.1 What Is Gluconeogenesis, and How Does It Operate? 755 The Substrates for Gluconeogenesis Include Pyruvate, Lactate, and Amino Acids 756 Nearly All Gluconeogenesis Occurs in the Liver and Kidneys in Animals 756 Human Biochemistry: The Chemistry of Glucose Monitoring Devices 756 Gluconeogenesis Is Not Merely the Reverse of Glycolysis 757 Gluconeogenesis—Something Borrowed, Something New 757 Four Reactions Are Unique to Gluconeogenesis 757 Human Biochemistry: Gluconeogenesis Inhibitors and Other Diabetes Therapy Strategies 762 22.2 How Is Gluconeogenesis Regulated? 763 Critical Developments in Biochemistry: The Pioneering Studies of Carl and Gerty Cori 763 Gluconeogenesis Is Regulated by Allosteric and Substrate-Level Control Mechanisms 764 A Deeper Look: TIGAR—a p53-Induced Enzyme That Mimics Fructose-2,6-Bisphosphatase 766 Substrate Cycles Provide Metabolic Control Mechanisms 767 22.3 How Are Glycogen and Starch Catabolized in Animals? 767 Dietary Starch Breakdown Provides Metabolic Energy 767 Metabolism of Tissue Glycogen Is Regulated 769 22.4 How Is Glycogen Synthesized? 769 Glucose Units Are Activated for Transfer by Formation of Sugar Nucleotides 769 UDP–Glucose Synthesis Is Driven by Pyrophosphate Hydrolysis 770 Glycogen Synthase Catalyzes Formation of a(18n4) Glycosidic Bonds in Glycogen 771 Glycogen Branching Occurs by Transfer of Terminal Chain Segments 771 Human Biochemistry: Advanced Glycation End Products—A Serious Complication of Diabetes 772 22.5 How Is Glycogen Metabolism Controlled? 773 Glycogen Metabolism Is Highly Regulated 773 Glycogen Synthase Is Regulated by Covalent Modification 773 Hormones Regulate Glycogen Synthesis and Degradation 775 A Deeper Look: Carbohydrate Utilization in Exercise 775 Human Biochemistry: von Gierke Disease— A Glycogen-Storage Disease 776 Critical Developments in Biochemistry: O-GlcNAc Signaling and the Hexosamine Biosynthetic Pathway 778 22.6 Can Glucose Provide Electrons for Biosynthesis? 780 The Pentose Phosphate Pathway Operates Mainly in Liver and Adipose Cells 780 The Pentose Phosphate Pathway Begins with Two Oxidative Steps 780 There Are Four Nonoxidative Reactions in the Pentose Phosphate Pathway 782 Human Biochemistry: Aldose Reductase and Diabetic Cataract Formation 783 Utilization of Glucose-6-P Depends on the Cell’s Need for ATP, NADPH, and Ribose-5-P 786 Critical Developments in Biochemistry: Integrating the Warburg Effect—ATP Consumption Promotes Cancer Metabolism 788 Xylulose-5-Phosphate Is a Metabolic Regulator 789 SUMMARY 790 Foundational Biochemistry 790 PROBLEMS 791 Further Reading 792 23 Fatty Acid Catabolism 795 23.1 How Are Fats Mobilized from Dietary Intake and Adipose Tissue? 795 Modern Diets Are Often High in Fat 795 Triacylglycerols Are a Major Form of Stored Energy in Animals 795 Hormones Trigger the Release of Fatty Acids from Adipose Tissue 796 Degradation of Dietary Triacylglycerols Occurs Primarily in the Duodenum 796 Human Biochemistry: Serum Albumin—Tramp Steamer of the Bloodstream 799 A Deeper Look: The Biochemistry of Obesity 800 23.2 How Are Fatty Acids Broken Down? 800 Knoop Elucidated the Essential Feature of b-Oxidation 800 Coenzyme A Activates Fatty Acids for Degradation 801 Carnitine Carries Fatty Acyl Groups Across the Inner Mitochondrial Membrane 802 b-Oxidation Involves a Repeated Sequence of Four Reactions 803 Repetition of the b-Oxidation Cycle Yields a Succession of Acetate Units 807 A Deeper Look: A Trifunctional Protein Complex Provides a Substrate Channeling Pathway for Fatty Acid Oxidation 808 Human Biochemistry: Exercise Can Reverse the Consequences of Metabolic Syndrome 809 Complete b-Oxidation of One Palmitic Acid Yields 106 Molecules of ATP 809 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 etoet0awlomg18stanGsonEneg RCoAggAcivationbyGtrate Fatty Acid Oxidation Is an Important Source of Metabolic Acyl Carrier Proteins Camry the Intermediates in Fatty Acid Water for Some Animals 811 Synthesis 830 23.3 How Are Odd-Carbon Fatty Acids Oxidized?812 B-Oxidation of Odd-Carbon Fatty Acids Yields Propionyl-CoA 812 ndensation of Acetyl-CoA and Malonyl-CoA 831 A DEEPER LOOK:Choosing the Best Organism for the of Succinyl-CoA Requires Conversion Expenment 83 to Acetyl-CoA 813 A DEEPER LOOK:The Activation of Vitamin B,,813 23.4 How Are Unsaturated Fatty Acids Oxidized?814 Euka otes Build Fatty Acidson Megasynthase Complexes 834 An Isomerase and a Reductase Facilitate the B-Oxidation of Unsaturated Fatty Acids814 C Fatty Acids May Undergo Elongation and Unsaturation 836 A DEEPER LOOK:Can olowed hy Chair oxidants in Certair Elongation 838 Mam 23.5 Are There Other Ways to Oxidize Fatty Acids?816 ao ee Mos Plnre Peroxisomal B-Oxida ion Requires Fad-Denenden Acyl-CoA Oxidase 816 om Linoleic Acid Are Degraded Via rol of Fatty Acid metabolism rplay of Allo ic Modifiers as Regulate HUMAN BIOCHEMISTRY:Refsum's Disease Is a Result of Defects in a-Oxidation 818 HUMAN BIOCHEMISTRY:3 and 6-Essential Fatty 23.6 What Are Ketone Bodies,and What Role Do They Play Acids with Many Functions 840 in Metabolism?818 242 How Are Complex Lipids Synthesized?841 urce of Fue Glyce tsof Ketone Bodie ol 842 B-Hydroxybutyrate Isa Signaling Metabolite19 hosphatases Essential SUMMARY 820 FOUNDATIONAL BIOCHEMISTRY 821 PRORLEMS 821 ine 843 of Eth FURTHER READING 823 FpgEhanolBminetoopoEeine84sS 24 Lipid Biosynthesis 825 241 for Fatty Acid Synthesis Activates Acetate Units Platelet-Activating Factor Is Formed by Acetylation oe2agitDpmtoneaeeo of 1-Alkvl-2-Lysophosphatidylcholine 848 for Other Sphingolipids Acetate Units AreC Acid Synthesis and Cerebrosides by Formation of 24.3 oids Synthesized,and What Are Acetyl-CoA Carboxylase Is Biotin Dependent Their Functions?851 and Displays Ping-F Pong Kinetics 828 Ficosanoids are local Hormones 85
xx Detailed Contents Migratory Birds Travel Long Distances on Energy from Fatty Acid Oxidation 810 Fatty Acid Oxidation Is an Important Source of Metabolic Water for Some Animals 811 23.3 How Are Odd-Carbon Fatty Acids Oxidized? 812 b-Oxidation of Odd-Carbon Fatty Acids Yields Propionyl-CoA 812 A B12-Catalyzed Rearrangement Yields Succinyl-CoA from l-Methylmalonyl-CoA 812 Net Oxidation of Succinyl-CoA Requires Conversion to Acetyl-CoA 813 A Deeper Look: The Activation of Vitamin B12 813 23.4 How Are Unsaturated Fatty Acids Oxidized? 814 An Isomerase and a Reductase Facilitate the b-Oxidation of Unsaturated Fatty Acids 814 Degradation of Polyunsaturated Fatty Acids Requires 2,4-Dienoyl-CoA Reductase 814 A Deeper Look: Can Natural Antioxidants in Certain Foods Improve Fat Metabolism? 816 23.5 Are There Other Ways to Oxidize Fatty Acids? 816 Peroxisomal b-Oxidation Requires FAD-Dependent Acyl-CoA Oxidase 816 Branched-Chain Fatty Acids Are Degraded Via a-Oxidation 817 v-Oxidation of Fatty Acids Yields Small Amounts of Dicarboxylic Acids 817 Human Biochemistry: Refsum’s Disease Is a Result of Defects in a-Oxidation 818 23.6 What Are Ketone Bodies, and What Role Do They Play in Metabolism? 818 Ketone Bodies Are a Significant Source of Fuel and Energy for Certain Tissues 818 Human Biochemistry: Large Amounts of Ketone Bodies Are Produced in Diabetes Mellitus 818 b-Hydroxybutyrate Is a Signaling Metabolite 819 SUMMARY 820 Foundational Biochemistry 821 PROBLEMS 821 Further Reading 823 24 Lipid Biosynthesis 825 24.1 How Are Fatty Acids Synthesized? 826 Formation of Malonyl-CoA Activates Acetate Units for Fatty Acid Synthesis 826 Fatty Acid Biosynthesis Depends on the Reductive Power of NADPH 826 Cells Must Provide Cytosolic Acetyl-CoA and Reducing Power for Fatty Acid Synthesis 826 Acetate Units Are Committed to Fatty Acid Synthesis by Formation of Malonyl-CoA 827 Acetyl-CoA Carboxylase Is Biotin Dependent and Displays Ping-Pong Kinetics 828 Acetyl-CoA Carboxylase in Animals Is a Multifunctional Protein 829 Phosphorylation of ACC Modulates Activation by Citrate and Inhibition by Palmitoyl-CoA 829 Acyl Carrier Proteins Carry the Intermediates in Fatty Acid Synthesis 830 In Some Organisms, Fatty Acid Synthesis Takes Place in Multienzyme Complexes 830 Decarboxylation Drives the Condensation of Acetyl-CoA and Malonyl-CoA 831 A Deeper Look: Choosing the Best Organism for the Experiment 831 Reduction of the b-Carbonyl Group Follows a Now-Familiar Route 833 Eukaryotes Build Fatty Acids on Megasynthase Complexes 834 C16 Fatty Acids May Undergo Elongation and Unsaturation 836 Unsaturation Reactions Occur in Eukaryotes in the Middle of an Aliphatic Chain 837 The Unsaturation Reaction May Be Followed by Chain Elongation 838 Mammals Cannot Synthesize Most Polyunsaturated Fatty Acids 838 Arachidonic Acid Is Synthesized from Linoleic Acid by Mammals 838 Regulatory Control of Fatty Acid Metabolism Is an Interplay of Allosteric Modifiers and Phosphorylation–Dephosphorylation Cycles 839 Hormonal Signals Regulate ACC and Fatty Acid Biosynthesis 839 Human Biochemistry: v3 and v6—Essential Fatty Acids with Many Functions 840 24.2 How Are Complex Lipids Synthesized? 841 Glycerolipids Are Synthesized by Phosphorylation and Acylation of Glycerol 842 Eukaryotes Synthesize Glycerolipids from CDP-Diacylglycerol or Diacylglycerol 842 Human Biochemistry: Lipins—Phosphatases Essential for Triglyceride Synthesis and Other Functions 842 Phosphatidylethanolamine Is Synthesized from Diacylglycerol and CDP-Ethanolamine 843 Exchange of Ethanolamine for Serine Converts Phosphatidylethanolamine to Phosphatidylserine 845 Eukaryotes Synthesize Other Phospholipids Via CDP-Diacylglycerol 845 Dihydroxyacetone Phosphate Is a Precursor to the Plasmalogens 845 Platelet-Activating Factor Is Formed by Acetylation of 1-Alkyl-2-Lysophosphatidylcholine 848 Sphingolipid Biosynthesis Begins with Condensation of Serine and Palmitoyl-CoA 848 Ceramide Is the Precursor for Other Sphingolipids and Cerebrosides 848 24.3 How Are Eicosanoids Synthesized, and What Are Their Functions? 851 Eicosanoids Are Local Hormones 851 Prostaglandins Are Formed from Arachidonate by Oxidation and Cyclization 851 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 A DEEPER LOOK:The discovery of prostaglandins 851 25 Nitrogen Acquisition and Amino Acid Metabolism 877 25.1 Which Metabolic Pathways Allow Organism to Live on Inorganic Forms of Nitrogen?877 Anti-Infar Eicosanoid Products of Transcelluar Metabolism and te E nment 8 NitrateAsimlationl 24.4 How Is Cholesterol Synthesized?856 ms Gain Access to Atr eric N Via Acety-CoA Via 25.2 What Is the Metabolic Fate of Ammonium?882 ase o 25.3 What Regulatory Mechanisms Act on Escherichiacol Glutamine Synthetase?886 Squalene Is Synthesized fr om Mevalonate 858 Glutamine Synthetase Is Allosterically Regulated88 CHEMISTRY:Statins Lower Serum Cholestero etases Regulated by Covaent 20Adhinalsepga62liocholesterolReguite of La hetase Is Regulated Through Gene 24.5 How Are Lipids Transported Throughout the Body?862 Glutamine in the Human Body 889 254 How Do Organisms Synthesize Amino Acids?890 HUMAN BIOCHEMISTRY:Human Dietary Requirements C3 protein or Amino Acids 891 rm-Ket Acids Lipoprotein Lipase 864 ADEEPER LOOK The Mechanism of the Aminotransferase The Structure of the LDL Receptor Involves Five Domains 865 Transamination)reaction 892 The LDL Receptor B-Propellor Displaces LDL Particles ndosomes 86 Families 89 SatmoleocMeuaboismcanleadtoEeraed The Urea Cycle Acts to Excrete Excess N Through Arg Chaperone Breakdown 894 Ammonium The Oxalo in Acids Includes Asp 24.6 How Are Bile Acids Biosynthesized?869 Asn.Lys.Met Thr.and lle 897 HUMAN BIOCHEMISTRY S id 50 Reductas A5aednesPmostatchpepash,and rostate Cancer 87 247 How A Utilized? The 3.Phosphoglycerate Family of Amino Acids Includes Ser,Gly.and Cys 903 The Aromatic Ar Steroid Hormones Modulate Transcription in the Nucleus 871 orisoland Other Corticosterds Regulate a Variety RLOOK Amino Acid Biosynthesis Inhibitors of Body Processes 871 as Herbicides 911 een Used llegally to Enhance SUMMARY 872 IONAL BIOCHEMISTRY 873 PROBLEMS 874 25.5 nto of En FURTHER READING 875
Detailed Contents xxi A Deeper Look: The Discovery of Prostaglandins 851 A Variety of Stimuli Trigger Arachidonate Release and Eicosanoid Synthesis 853 “Take Two Aspirin and . . . ” Inhibit Your Prostaglandin Synthesis 853 Human Biochemistry: Lipoxins—Anti-Inflammatory Eicosanoid Products of Transcellular Metabolism 854 A Deeper Look: The Molecular Basis for the Action of Nonsteroidal Anti-inflammatory Drugs 855 24.4 How Is Cholesterol Synthesized? 856 Mevalonate Is Synthesized from Acetyl-CoA Via HMG-CoA Synthase 856 A Thiolase Brainteaser Asks Why Thiolase Can’t Be Used in Fatty Acid Synthesis 857 Critical Developments in Biochemistry: The Long Search for the Route of Cholesterol Biosynthesis 858 Squalene Is Synthesized from Mevalonate 858 Human Biochemistry: Statins Lower Serum Cholesterol Levels 860 Conversion of Lanosterol to Cholesterol Requires 20 Additional Steps 862 24.5 How Are Lipids Transported Throughout the Body? 862 Lipoprotein Complexes Transport Triacylglycerols and Cholesterol Esters 862 Human Biochemistry: APOC3—An Apolipoprotein That Regulates Plasma Triglyceride Levels 864 Lipoproteins in Circulation Are Progressively Degraded by Lipoprotein Lipase 864 The Structure of the LDL Receptor Involves Five Domains 865 The LDL Receptor b-Propellor Displaces LDL Particles in Endosomes 866 Defects in Lipoprotein Metabolism Can Lead to Elevated Serum Cholesterol 866 Human Biochemistry: New Cholesterol-Lowering Drugs Target PCSK9, an LDL Receptor Chaperone 867 Human Biochemistry: Niemann—Pick Type C Disease—A Hydrophobic Handoff Fumbled 868 24.6 How Are Bile Acids Biosynthesized? 869 Human Biochemistry: Steroid 5a—Reductase— A Factor in Male Baldness, Prostatic Hyperplasia, and Prostate Cancer 870 24.7 How Are Steroid Hormones Synthesized and Utilized? 870 Pregnenolone and Progesterone Are the Precursors of All Other Steroid Hormones 870 Steroid Hormones Modulate Transcription in the Nucleus 871 Cortisol and Other Corticosteroids Regulate a Variety of Body Processes 871 Anabolic Steroids Have Been Used Illegally to Enhance Athletic Performance 872 SUMMARY 872 Foundational Biochemistry 873 PROBLEMS 874 Further Reading 875 25 Nitrogen Acquisition and Amino Acid Metabolism 877 25.1 Which Metabolic Pathways Allow Organisms to Live on Inorganic Forms of Nitrogen? 877 Nitrogen Is Cycled Between Organisms and the Inanimate Environment 877 Nitrate Assimilation Is the Principal Pathway for Ammonium Biosynthesis 878 Organisms Gain Access to Atmospheric N2 Via the Pathway of Nitrogen Fixation 879 25.2 What Is the Metabolic Fate of Ammonium? 882 The Major Pathways of Ammonium Assimilation Lead to Glutamine Synthesis 884 25.3 What Regulatory Mechanisms Act on Escherichia coli Glutamine Synthetase? 886 Glutamine Synthetase Is Allosterically Regulated 887 Glutamine Synthetase Is Regulated by Covalent Modification 887 Glutamine Synthetase Is Regulated Through Gene Expression 889 Glutamine in the Human Body 889 25.4 How Do Organisms Synthesize Amino Acids? 890 Human Biochemistry: Human Dietary Requirements for Amino Acids 891 Amino Acids Are Formed from a-Keto Acids by Transamination 891 A Deeper Look: The Mechanism of the Aminotransferase (Transamination) Reaction 892 The Pathways of Amino Acid Biosynthesis Can Be Organized into Families 892 The a-Ketoglutarate Family of Amino Acids Includes Glu, Gln, Pro, Arg, and Lys 893 The Urea Cycle Acts to Excrete Excess N Through Arg Breakdown 894 A Deeper Look: The Urea Cycle as Both an Ammonium and a Bicarbonate Disposal Mechanism 897 The Oxaloacetate Family of Amino Acids Includes Asp, Asn, Lys, Met, Thr, and Ile 897 Human Biochemistry: Asparagine and Leukemia 899 The Pyruvate Family of Amino Acids Includes Ala, Val, and Leu 903 The 3-Phosphoglycerate Family of Amino Acids Includes Ser, Gly, and Cys 903 The Aromatic Amino Acids Are Synthesized from Chorismate 907 A Deeper Look: Amino Acid Biosynthesis Inhibitors as Herbicides 911 A Deeper Look: Intramolecular Tunnels Connect Distant Active Sites in Some Enzymes 912 Histidine Biosynthesis and Purine Biosynthesis Are Connected by Common Intermediates 912 25.5 How Does Amino Acid Catabolism Lead into Pathways of Energy Production? 914 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 he 20 Co nmo 26.6 How Are Pyrimidines Degraded?946 26.7 How Do Cells Form the Deoxyribonucleotides A DEEPER LOOK:Histidine-A Clue to Understanding That Are Necessary for DNA Synthesis?946 Early Evo A8-Elimination 917 Serine Dehydratase Reaction oxin Pr Animals Differ in the Form of Nitrogen That They Excrete 921 HUMAN BIOCHEMISTRY:Hereditary Defects in Phe Both the the Catabolism Underlie Alkaptonuria and Phenylketonuria 927 SUMMARY 922 26.8 How Are Thymine Nucleotides S FOUNDATIONAL BIOCHEMISTRY 923 PROBLEMS 924 as Therapeutic Agents 951 FURTHER READING 925 HUMAN BIOCHEMISTRY:Fluoro-Substituted Pyrimidines therapy,Fungal Infections, 26 Synthesis and Degradation of Nucleotides 927 and Malaria 952 Can Cells Synthesize Nucleotides?97 SUMMARY 952 26.2 How Do Cells Synthesize Purines?928 FOUNDATIONAL BIOCHEMISTRY IMP Is the Immediate Precursor to GMP and AMP 928 PROBLEMS 95 toiEpE8LookTetahdolaieand0neCabon FURTHER READING 955 27 Metabolic Integration and Organ HUMAN BIOCHEMISTRY:Folate Analogs as Antimicrobial Specialization 957 27.1 ed from IMP933 Only a Few Intermediates Interconect the Major Metabolic Systems959 ATP.De ndent Kinases Form Nucleoside Diphosphates and ATP and NADPH Couple Anabolism and Catabolism 959 Triphosphates from the Nucleoside Monophosphates 935 26.3 Can Cells Salvage Purines?936 26.4 How are purines degr 272 eminesthek ATP Has Two Metabolic Roles 961 27.3 Is There a Good Index of Cellular En Status?961 Deaminase Is One Cause of This Inherited Disease 938 es the ATP Levels to the Total Adenin Key Enzymes Are Regulated by Energy Charge 962 Gout is a Disease Caused by an Excess of Uric Acid 935 PoeMerof Relaive Different Anin nals oxidize uric acid to for n Variou 27.4 Excretory Products 941 rall Energy Balance Regulatec 6 26.5 How do Cells Synthesize Pyrimidines?941 mes in Energy Production "Metabolic Channeling"by Multifunctional Enzymes of Mammalian Pyrimidine Biosynthesis 943 AMPK Controls Whole-Body Energy Homeostasis 965 27.5 ated in a multicellular Factor 944 Organism?966 UMP Synthesis Leads to Formation of the Two Most Prominent Ribonucleotides JTP and CTP 944
xxii Detailed Contents The 20 Common Amino Acids Are Degraded by 20 Different Pathways That Converge to Just 7 Metabolic Intermediates 914 A Deeper Look: Histidine—A Clue to Understanding Early Evolution? 915 A Deeper Look: The Serine Dehydratase Reaction— A b-Elimination 917 Animals Differ in the Form of Nitrogen That They Excrete 921 Human Biochemistry: Hereditary Defects in Phe Catabolism Underlie Alkaptonuria and Phenylketonuria 921 SUMMARY 922 Foundational Biochemistry 923 PROBLEMS 924 Further Reading 925 26 Synthesis and Degradation of Nucleotides 927 26.1 Can Cells Synthesize Nucleotides? 927 26.2 How Do Cells Synthesize Purines? 928 IMP Is the Immediate Precursor to GMP and AMP 928 A Deeper Look: Tetrahydrofolate and One-Carbon Units 930 HUMAN BIOCHEMISTRY: SAICAR Is a Key Signal for Metabolic Reprogramming in Cancer Cells 932 Human Biochemistry: Folate Analogs as Antimicrobial and Anticancer Agents 933 AMP and GMP Are Synthesized from IMP 933 The Purine Biosynthetic Pathway Is Regulated at Several Steps 934 ATP-Dependent Kinases Form Nucleoside Diphosphates and Triphosphates from the Nucleoside Monophosphates 935 26.3 Can Cells Salvage Purines? 936 26.4 How Are Purines Degraded? 936 Human Biochemistry: Lesch—Nyhan Syndrome— HGPRT Deficiency Leads to a Severe Clinical Disorder 937 The Major Pathways of Purine Catabolism Lead to Uric Acid 937 Human Biochemistry: Severe Combined Immunodeficiency Syndrome—A Lack of Adenosine Deaminase Is One Cause of This Inherited Disease 938 The Purine Nucleoside Cycle in Skeletal Muscle Serves as an Anaplerotic Pathway 938 Xanthine Oxidase 938 Gout Is a Disease Caused by an Excess of Uric Acid 939 Different Animals Oxidize Uric Acid to Form Various Excretory Products 941 26.5 How Do Cells Synthesize Pyrimidines? 941 “Metabolic Channeling” by Multifunctional Enzymes of Mammalian Pyrimidine Biosynthesis 943 Human Biochemistry: Mammalian CPS-II Is Activated In Vitro by MAP Kinase and In Vivo by Epidermal Growth Factor 944 UMP Synthesis Leads to Formation of the Two Most Prominent Ribonucleotides—UTP and CTP 944 Pyrimidine Biosynthesis Is Regulated at ATCase in Bacteria and at CPS-II in Animals 944 26.6 How Are Pyrimidines Degraded? 946 26.7 How Do Cells Form the Deoxyribonucleotides That Are Necessary for DNA Synthesis? 946 E. coli Ribonucleotide Reductase Has Three Different Nucleotide-Binding Sites 946 Thioredoxin Provides the Reducing Power for Ribonucleotide Reductase 947 Both the Specificity and the Catalytic Activity of Ribonucleotide Reductase Are Regulated by Nucleotide Binding 948 26.8 How Are Thymine Nucleotides Synthesized? 949 A Deeper Look: Fluoro-Substituted Analogs as Therapeutic Agents 951 Human Biochemistry: Fluoro-Substituted Pyrimidines in Cancer Chemotherapy, Fungal Infections, and Malaria 952 SUMMARY 952 Foundational Biochemistry 953 PROBLEMS 954 Further Reading 955 27 Metabolic Integration and Organ Specialization 957 27.1 Can Systems Analysis Simplify the Complexity of Metabolism? 957 Only a Few Intermediates Interconnect the Major Metabolic Systems 959 ATP and NADPH Couple Anabolism and Catabolism 959 Phototrophs Have an Additional Metabolic System— The Photochemical Apparatus 959 27.2 What Underlying Principle Relates ATP Coupling to the Thermodynamics of Metabolism? 959 ATP Coupling Stoichiometry Determines the Keq for Metabolic Sequences 961 ATP Has Two Metabolic Roles 961 27.3 Is There a Good Index of Cellular Energy Status? 961 Adenylate Kinase Interconverts ATP, ADP, and AMP 962 Energy Charge Relates the ATP Levels to the Total Adenine Nucleotide Pool 962 Key Enzymes Are Regulated by Energy Charge 962 Phosphorylation Potential Is a Measure of Relative ATP Levels 963 27.4 How Is Overall Energy Balance Regulated in Cells? 963 AMPK Targets Key Enzymes in Energy Production and Consumption 964 AMPK Controls Whole-Body Energy Homeostasis 965 27.5 How Is Metabolism Integrated in a Multicellular Organism? 966 The Major Organ Systems Have Specialized Metabolic Roles 966 Human Biochemistry: Athletic Performance Enhancement with Creatine Supplements? 969 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