XX Contents 11.2 Membrane Dynamics 395 BOX 12-2 MEDICINE:G Proteins:Binary Switches in Health Acyl Groups in the Bilayer Interior Are Ordered to Tran of Lipids Requires 395 444 396 sitized b Phosphorylation and by Association with the Bilaye d Cholesterol Cluster Together in 46 398 egulatory 446 usion Are Central to and Ca* 399 Relat nd Me er 447 ETHODS :BI aling 402 cond Me enger That may be 402 GPCRs Mediate the actions of a wide variety of Proteins SIgnals 452 nels ar Fundamentally Different 吃 12.3 Receptor Tyrosine Kinase Th de of protein ph lation Reactions 46 The M dPIPs Funct tions at a 456 System Also Involves he Pla an The JAK-STAT Sna N:Def Cross Talk among Signaling Systems Is Common 457 ose and Water 408 and Comple 458 12.4 Rece 409 Protein KinaseG 459 p.Type ATPa ases Undergo Phosphorylation during pe ATPase 410 12.5 Multivalent Adaptor Proteins and Membrane es are reversible 412 Raft 460 e the active in Modules Bind Phosphorylated Tyr,Ser,o iety of Substrate Thr Resic ues in Partner Proteins 460 Caveolae May Segregate 463 12.6 Gated lon Channels Ion Channels Underlie Electrical Signaling in n Hydrophilic Transmembrane nnels Allow Rapid Movement 418 olhgeeeShchammesrotoeNeuonal 464 465 eceptor Is a Ligand-Gated Ion 1 Electrically 467 422 Gated Ion Channels Are Central in Neuronal 468 Toxins Target Ion Channels 468 De unctio Channels can Have Severe Physiological Consequences 470 12 Biosignaling 433 12.8 Regulation ofTrans 433 Hormone Receptor 471 3dlnteractio 12.Signaling in Microorga 473 the Rerent 12.2 G Protein-Coupled Receptors and Second o-C mponent System ion in a 473 Messengers 437 473 CAp Acts throh Plants Dete a Two-Componen 438 475
11.2 Membrane Dynamics 395 Acyl Groups in the Bilayer Interior Are Ordered to Varying Degrees 395 Transbilayer Movement of Lipids Requires Catalysis 396 Lipids and Proteins Diffuse Laterally in the Bilayer 397 Sphingolipids and Cholesterol Cluster Together in Membrane Rafts 398 Membrane Curvature and Fusion Are Central to Many Biological Processes 399 Integral Proteins of the Plasma Membrane Are Involved in Surface Adhesion, Signaling, and Other Cellular Processes 402 11.3 Solute Transport across Membranes 402 Passive Transport Is Facilitated by Membrane Proteins 403 Transporters and Ion Channels Are Fundamentally Different 404 The Glucose Transporter of Erythrocytes Mediates Passive Transport 405 The Chloride-Bicarbonate Exchanger Catalyzes Electroneutral Cotransport of Anions across the Plasma Membrane 407 BOX 11–1 MEDICINE: Defective Glucose and Water Transport in Two Forms of Diabetes 408 Active Transport Results in Solute Movement against a Concentration or Electrochemical Gradient 409 P-Type ATPases Undergo Phosphorylation during Their Catalytic Cycles 410 V-Type and F-Type ATPases Are Reversible, ATP-Driven Proton Pumps 412 ABC Transporters Use ATP to Drive the Active Transport of a Wide Variety of Substrates 413 Ion Gradients Provide the Energy for Secondary Active Transport 414 BOX 11–2 MEDICINE: A Defective Ion Channel in Cystic Fibrosis 415 Aquaporins Form Hydrophilic Transmembrane Channels for the Passage of Water 418 Ion-Selective Channels Allow Rapid Movement of Ions across Membranes 420 Ion-Channel Function Is Measured Electrically 421 The Structure of a K1 Channel Reveals the Basis for Its Specificity 422 Gated Ion Channels Are Central in Neuronal Function 424 Defective Ion Channels Can Have Severe Physiological Consequences 424 12 Biosignaling 433 12.1 General Features of Signal Transduction 433 BOX 12–1 METHODS: Scatchard Analysis Quantifies the Receptor-Ligand Interaction 435 12.2 G Protein–Coupled Receptors and Second Messengers 437 The -Adrenergic Receptor System Acts through the Second Messenger cAMP 438 BOX 12–2 MEDICINE: G Proteins: Binary Switches in Health and Disease 441 Several Mechanisms Cause Termination of the -Adrenergic Response 444 The -Adrenergic Receptor Is Desensitized by Phosphorylation and by Association with Arrestin 445 Cyclic AMP Acts as a Second Messenger for Many Regulatory Molecules 446 Diacylglycerol, Inositol Trisphosphate, and Ca21 Have Related Roles as Second Messengers 447 BOX 12–3 METHODS: FRET: Biochemistry Visualized in a Living Cell 448 Calcium Is a Second Messenger That May Be Localized in Space and Time 451 GPCRs Mediate the Actions of a Wide Variety of Signals 452 12.3 Receptor Tyrosine Kinases 453 Stimulation of the Insulin Receptor Initiates a Cascade of Protein Phosphorylation Reactions 453 The Membrane Phospholipid PIP3 Functions at a Branch in Insulin Signaling 456 The JAK-STAT Signaling System Also Involves Tyrosine Kinase Activity 457 Cross Talk among Signaling Systems Is Common and Complex 458 12.4 Receptor Guanylyl Cyclases, cGMP, and Protein Kinase G 459 12.5 Multivalent Adaptor Proteins and Membrane Rafts 460 Protein Modules Bind Phosphorylated Tyr, Ser, or Thr Residues in Partner Proteins 460 Membrane Rafts and Caveolae May Segregate Signaling Proteins 463 12.6 Gated Ion Channels 464 Ion Channels Underlie Electrical Signaling in Excitable Cells 464 Voltage-Gated Ion Channels Produce Neuronal Action Potentials 465 The Acetylcholine Receptor Is a Ligand-Gated Ion Channel 467 Neurons Have Receptor Channels That Respond to Different Neurotransmitters 468 Toxins Target Ion Channels 468 12.7 Integrins: Bidirectional Cell Adhesion Receptors 470 12.8 Regulation of Transcription by Nuclear Hormone Receptors 471 12.9 Signaling in Microorganisms and Plants 473 Bacterial Signaling Entails Phosphorylation in a Two-Component System 473 Signaling Systems of Plants Have Some of the Same Components Used by Microbes and Mammals 473 Plants Detect Ethylene through a Two-Component System and a MAPK Cascade 475 xx Contents FMTOC.indd Page xx 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
Contents xxi Raecplareptet血aasesTansdoeSerab 522 46 oups 12.10 Sensory Transduction in Vision,Olfaction, 523 ational Macromolecule and Gustation 477 524 The Visual System Uses Classic GPCR 525 477 Excited Rhodo Contraction 526 CoeeseliahcTmted 527 BOX12-4 MEDICINE:Color Blindness:John Dalton's 8 13.4 Biological Oxidation-Reduction Reactions 528 528 Mechanisms Similar to the Visual System whGrCRsotHoneSengsFa 528 482 drogenatio 12.11 Regulation of the Cell Cyde by Protein Kinases 484 of Cen-Dependent Protein Kinases 84 gy Chang Carbon Dioxide 63 eCell Division by Phosphorylating ron Car 532 Critical Proteins 487 pressor Genes,and 532 NADH and NADPH Act with Dehydrogenases as Programme 488 f the genes for d NAD in,the Vitamin Form 535 s on Cell Division ove Norm e 489 535 MEDICINE:Development of Protein Kinase Glycolysis,Gluconeogenesis,and Apoptosis IsPro Cell Suicide 482 4 the Pentose Phosphate Pathway 543 II BIOENERGETICS AND METABOLISM 501 14.1 Glycolysis ires ATP 548 13 Bioenergetics and Biochemical The Pa hase of Glycolysis Yields ATI Reaction Types 505 The d rall Balance Sheet Shows a Net Gain 13.1 Bioenergetics and Thermodynamics 506 sis is under Tight regulation BioloegicalFnewTanstormationsObeythe 09 B14-1 MEDICNE:High Rate of in Tumors Cells Require Sources of Free Ene gests Targets for otnerapy and Facilitates 50 e Uptake Is Deficient in Type 1 Diabetes Reactant 558 Standard Free-Energy Changes Are Additive 14.2 Feeder Pathways for Glycolysis 558 Dietary Polysaccharides and Disac 13.2 Chemical Logic and Common Biochemical 558 End us Gly nand Starch Are Degraded Biochemical and Chemical Equations Are Not 560 Identical 517 Pathway at Several Points 561 13.3 Phosphoryl Group Transfers and ATP The Free-Energy Change for ATP Hydrolysis 14.3 Fates of Pyruvate under 563 ounds and Thioester ninal Electron Acceptor in arge Free Energies of Hydrolysis 520 cid Fer tation 63 oup Transters,N
Receptorlike Protein Kinases Transduce Signals from Peptides 476 12.10 Sensory Transduction in Vision, Olfaction, and Gustation 477 The Visual System Uses Classic GPCR Mechanisms 477 Excited Rhodopsin Acts through the G Protein Transducin to Reduce the cGMP Concentration 478 The Visual Signal Is Quickly Terminated 480 Cone Cells Specialize in Color Vision 480 BOX 12–4 MEDICINE: Color Blindness: John Dalton’s Experiment from the Grave 481 Vertebrate Olfaction and Gustation Use Mechanisms Similar to the Visual System 481 GPCRs of the Sensory Systems Share Several Features with GPCRs of Hormone Signaling Systems 482 12.11 Regulation of the Cell Cycle by Protein Kinases 484 The Cell Cycle Has Four Stages 484 Levels of Cyclin-Dependent Protein Kinases Oscillate 484 CDKs Regulate Cell Division by Phosphorylating Critical Proteins 487 12.12 Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death 488 Oncogenes Are Mutant Forms of the Genes for Proteins That Regulate the Cell Cycle 489 Defects in Certain Genes Remove Normal Restraints on Cell Division 489 BOX 12–5 MEDICINE: Development of Protein Kinase Inhibitors for Cancer Treatment 490 Apoptosis Is Programmed Cell Suicide 492 II BIOENERGETICS AND METABOLISM 501 13 Bioenergetics and Biochemical Reaction Types 505 13.1 Bioenergetics and Thermodynamics 506 Biological Energy Transformations Obey the Laws of Thermodynamics 506 Cells Require Sources of Free Energy 507 Standard Free-Energy Change Is Directly Related to the Equilibrium Constant 507 Actual Free-Energy Changes Depend on Reactant and Product Concentrations 509 Standard Free-Energy Changes Are Additive 510 13.2 Chemical Logic and Common Biochemical Reactions 511 Biochemical and Chemical Equations Are Not Identical 517 13.3 Phosphoryl Group Transfers and ATP 517 The Free-Energy Change for ATP Hydrolysis Is Large and Negative 518 Other Phosphorylated Compounds and Thioesters Also Have Large Free Energies of Hydrolysis 520 ATP Provides Energy by Group Transfers, Not by Simple Hydrolysis 522 ATP Donates Phosphoryl, Pyrophosphoryl, and Adenylyl Groups 523 Assembly of Informational Macromolecules Requires Energy 524 BOX 13–1 Firefly Flashes: Glowing Reports of ATP 525 ATP Energizes Active Transport and Muscle Contraction 525 Transphosphorylations between Nucleotides Occur in All Cell Types 526 Inorganic Polyphosphate Is a Potential Phosphoryl Group Donor 527 13.4 Biological Oxidation-Reduction Reactions 528 The Flow of Electrons Can Do Biological Work 528 Oxidation-Reductions Can Be Described as Half-Reactions 528 Biological Oxidations Often Involve Dehydrogenation 529 Reduction Potentials Measure Affinity for Electrons 530 Standard Reduction Potentials Can Be Used to Calculate Free-Energy Change 531 Cellular Oxidation of Glucose to Carbon Dioxide Requires Specialized Electron Carriers 532 A Few Types of Coenzymes and Proteins Serve as Universal Electron Carriers 532 NADH and NADPH Act with Dehydrogenases as Soluble Electron Carriers 532 Dietary Deficiency of Niacin, the Vitamin Form of NAD and NADP, Causes Pellagra 535 Flavin Nucleotides Are Tightly Bound in Flavoproteins 535 14 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway 543 14.1 Glycolysis 544 An Overview: Glycolysis Has Two Phases 544 The Preparatory Phase of Glycolysis Requires ATP 548 The Payoff Phase of Glycolysis Yields ATP and NADH 550 The Overall Balance Sheet Shows a Net Gain of ATP 555 Glycolysis Is under Tight Regulation 555 BOX 14–1 MEDICINE: High Rate of Glycolysis in Tumors Suggests Targets for Chemotherapy and Facilitates Diagnosis 556 Glucose Uptake Is Deficient in Type 1 Diabetes Mellitus 558 14.2 Feeder Pathways for Glycolysis 558 Dietary Polysaccharides and Disaccharides Undergo Hydrolysis to Monosaccharides 558 Endogenous Glycogen and Starch Are Degraded by Phosphorolysis 560 Other Monosaccharides Enter the Glycolytic Pathway at Several Points 561 14.3 Fates of Pyruvate under Anaerobic Conditions: Fermentation 563 Pyruvate Is the Terminal Electron Acceptor in Lactic Acid Fermentation 563 BOX 14–2 Athletes, Alligators, and Coelacanths: Contents xxi FMTOC.indd Page xxi 19/10/12 1:36 PM user-F408 /Users/user-F408/Desktop
xxii Contents BOX14-2 Athletes,Alligators,and Coelacanths: 564 rol Analysis Has Bee 698 565 Applied to hate Carries“Active hyde Group 599 i:Brewing Beerand 566 566 15.3 Coordinated Regulation of Glycolysis and 14.4 Gluconeogenesis Gluconeogenesis 601 Con n of Pyruvate to Pho sphoenolpyruvate 570 602 Co hate to B0X15-2 602 Co Is the Third Bypas Hex kinas V(GI aseliyRegbted60 sisphosphatase Are Reciprocally 604 Fructos e 2.6-Bisp 605 and i 574 606 14.5 Pentose Phosphate Pathway of Glucose The Gly ate Kinase Is 575 The Gh ited by AT 66 ces Pentose hospho 575 608 14-4 MEDICINE:Why Pythagoras Wouldn't Eat Falafel: ion of Glycolysis and 76 ao G Is phate 577 BOX15-3 MEDICINE:Genetic Mutations That Lead to rbated by Rare Forms of Diabetes 580 611 612 580 613 15 Principles of Metabolic Regulation 587 colysisor 614 15.1 Requlation of Metabolic Pathways The Sugar Nuck otide UDP-Gc se Donates Cells and Organisms Maintain a Dynamic 615 ady State BOX15-4 Carl and Gert Meta sm and Dis 616 689 he Initial Sugar Residues in Ader 15.5 Coordinated Regulation of Glycogen Sunthesis and Breakdown 620 15.2 Analysis of Metabolic Control s96 Glycogen Phosphorylase Is Regulated Allosterically 621 The e Is Also Regulated by 596 me of the Actions of Insul▣ 624 597 ase 1 Is Central to to Cha 624 597 624 Quantitati 59g
BOX 14–2 Athletes, Alligators, and Coelacanths: Glycolysis at Limiting Concentrations of Oxygen 564 Ethanol Is the Reduced Product in Ethanol Fermentation 565 Thiamine Pyrophosphate Carries “Active Acetaldehyde” Groups 565 BOX 14–3 Ethanol Fermentations: Brewing Beer and Producing Biofuels 566 Fermentations Are Used to Produce Some Common Foods and Industrial Chemicals 566 14.4 Gluconeogenesis 568 Conversion of Pyruvate to Phosphoenolpyruvate Requires Two Exergonic Reactions 570 Conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphate Is the Second Bypass 572 Conversion of Glucose 6-Phosphate to Glucose Is the Third Bypass 573 Gluconeogenesis Is Energetically Expensive, but Essential 573 Citric Acid Cycle Intermediates and Some Amino Acids Are Glucogenic 574 Mammals Cannot Convert Fatty Acids to Glucose 574 Glycolysis and Gluconeogenesis Are Reciprocally Regulated 574 14.5 Pentose Phosphate Pathway of Glucose Oxidation 575 The Oxidative Phase Produces Pentose Phosphates and NADPH 575 BOX 14–4 MEDICINE: Why Pythagoras Wouldn’t Eat Falafel: Glucose 6-Phosphate Dehydrogenase Deficiency 576 The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate 577 Wernicke-Korsakoff Syndrome Is Exacerbated by a Defect in Transketolase 580 Glucose 6-Phosphate Is Partitioned between Glycolysis and the Pentose Phosphate Pathway 580 15 Principles of Metabolic Regulation 587 15.1 Regulation of Metabolic Pathways 588 Cells and Organisms Maintain a Dynamic Steady State 589 Both the Amount and the Catalytic Activity of an Enzyme Can Be Regulated 589 Reactions Far from Equilibrium in Cells Are Common Points of Regulation 592 Adenine Nucleotides Play Special Roles in Metabolic Regulation 594 15.2 Analysis of Metabolic Control 596 The Contribution of Each Enzyme to Flux through a Pathway Is Experimentally Measurable 596 The Flux Control Coefficient Quantifies the Effect of a Change in Enzyme Activity on Metabolite Flux through a Pathway 597 The Elasticity Coefficient Is Related to an Enzyme’s Responsiveness to Changes in Metabolite or Regulator Concentrations 597 BOX 15–1 METHODS: Metabolic Control Analysis: Quantitative Aspects 598 The Response Coefficient Expresses the Effect of an Outside Controller on Flux through a Pathway 598 Metabolic Control Analysis Has Been Applied to Carbohydrate Metabolism, with Surprising Results 599 Metabolic Control Analysis Suggests a General Method for Increasing Flux through a Pathway 600 15.3 Coordinated Regulation of Glycolysis and Gluconeogenesis 601 Hexokinase Isozymes of Muscle and Liver Are Affected Differently by Their Product, Glucose 6-Phosphate 602 BOX 15–2 Isozymes: Different Proteins That Catalyze the Same Reaction 602 Hexokinase IV (Glucokinase) and Glucose 6-Phosphatase Are Transcriptionally Regulated 603 Phosphofructokinase-1 and Fructose 1,6-Bisphosphatase Are Reciprocally Regulated 604 Fructose 2,6-Bisphosphate Is a Potent Allosteric Regulator of PFK-1 and FBPase-1 605 Xylulose 5-Phosphate Is a Key Regulator of Carbohydrate and Fat Metabolism 606 The Glycolytic Enzyme Pyruvate Kinase Is Allosterically Inhibited by ATP 606 The Gluconeogenic Conversion of Pyruvate to Phosphoenol Pyruvate Is Under Multiple Types of Regulation 608 Transcriptional Regulation of Glycolysis and Gluconeogenesis Changes the Number of Enzyme Molecules 608 BOX 15–3 MEDICINE: Genetic Mutations That Lead to Rare Forms of Diabetes 611 15.4 The Metabolism of Glycogen in Animals 612 Glycogen Breakdown Is Catalyzed by Glycogen Phosphorylase 613 Glucose 1-Phosphate Can Enter Glycolysis or, in Liver, Replenish Blood Glucose 614 The Sugar Nucleotide UDP-Glucose Donates Glucose for Glycogen Synthesis 615 BOX 15–4 Carl and Gerty Cori: Pioneers in Glycogen Metabolism and Disease 616 Glycogenin Primes the Initial Sugar Residues in Glycogen 619 15.5 Coordinated Regulation of Glycogen Synthesis and Breakdown 620 Glycogen Phosphorylase Is Regulated Allosterically and Hormonally 621 Glycogen Synthase Is Also Regulated by Phosphorylation and Dephosphorylation 623 Glycogen Synthase Kinase 3 Mediates Some of the Actions of Insulin 624 Phosphoprotein Phosphatase 1 Is Central to Glycogen Metabolism 624 Allosteric and Hormonal Signals Coordinate Carbohydrate Metabolism Globally 624 Carbohydrate and Lipid Metabolism Are Integrated by Hormonal and Allosteric Mechanisms 626 xxii Contents FMTOC.indd Page xxii 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
Contents xxiii 16 The CitricAcid Cycle 633 16.1 Production of Acetyl-CoA(Activated Acetate)633 BOX17-1 Fat Bears Carry Out B Oxidation in TheirSleep 676 634 d Fatty Acids Requires 677 634 -Number Fatty Acids The Pyruvate D 677 685 678 Leave the Enzyme Surface 62 16.2 Reactions of the Citric Acid Cycle BOX17-2 Coenzyme B:A RadicalSolution toa 638 680 in the citric acid Plant Per Than One Job 642 e and ynthet Precu 683 sof Different Organelles Names Are Confusing! The -n ons in the Cycle Is Efficiently The OitationofFal 684 BOX16-3 Citrate:ASymmetric Molecule That Reacts Phytanic Acid UndergoesOxidation in n of acetate so complicated? 48 17.3 Ketone Bodies 686 ents Are Importan 650 Anaplerotic Reactions Replenish Citric Acid Cycle Keton e Bodies Are Ove Diabetes 686 688 16.3 Regulation of the Citric Acid Cycle 子 Amino Acid Oxidation and the Pro Production of Urea 695 eric and Co 654 18.1 Metabolic Fates of Amino Groups 696 The id Cycle Is Regulated at Its Three Degraded to 697 Pyridoxal Phosphate Participates in the Transfer 65 69 16.4 The Glyoxylate Cyc 656 Produces Four-Carbon Compounds from Acetate 657 Ammonia Is Toxic to Animals late Cycles Are 704 17 Fatty Acid Catabolism 667 s Can Be Linked 17.1 Digestion,Mobilization,and Transport of Fats 668 The Activity of the Urea Cycle Is Reguated at 708 668 Path nnecti s Reduce the Energetic 669 B0X18-1 for Tiesue n 708 Ge ic Defects in the Urea Cycle Can Be Life 670 Threatening 709 17.2 Oxidation of Fatty Acids 672 18.3 Pathways of Amino Acid Degradation 710 oof Saturated Fatty Acids Has Four sorOeArminoAcidsAreConrertedtoGucose, Seve Cofactors Play mportant Roles cety 674 in Amino Ac 712
16 The Citric Acid Cycle 633 16.1 Production of Acetyl-CoA (Activated Acetate) 633 Pyruvate Is Oxidized to Acetyl-CoA and CO2 634 The Pyruvate Dehydrogenase Complex Requires Five Coenzymes 634 The Pyruvate Dehydrogenase Complex Consists of Three Distinct Enzymes 635 In Substrate Channeling, Intermediates Never Leave the Enzyme Surface 636 16.2 Reactions of the Citric Acid Cycle 638 The Sequence of Reactions in the Citric Acid Cycle Makes Chemical Sense 638 The Citric Acid Cycle Has Eight Steps 640 BOX 16–1 Moonlighting Enzymes: Proteins with More Than One Job 642 BOX 16–2 Synthases and Synthetases; Ligases and Lyases; Kinases, Phosphatases, and Phosphorylases: Yes, the Names Are Confusing! 646 The Energy of Oxidations in the Cycle Is Efficiently Conserved 647 BOX 16–3 Citrate: A Symmetric Molecule That Reacts Asymmetrically 648 Why Is the Oxidation of Acetate So Complicated? 649 Citric Acid Cycle Components Are Important Biosynthetic Intermediates 650 Anaplerotic Reactions Replenish Citric Acid Cycle Intermediates 650 Biotin in Pyruvate Carboxylase Carries CO2 Groups 651 16.3 Regulation of the Citric Acid Cycle 653 Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex Is Regulated by Allosteric and Covalent Mechanisms 654 The Citric Acid Cycle Is Regulated at Its Three Exergonic Steps 655 Substrate Channeling through Multienzyme Complexes May Occur in the Citric Acid Cycle 655 Some Mutations in Enzymes of the Citric Acid Cycle Lead to Cancer 656 16.4 The Glyoxylate Cycle 656 The Glyoxylate Cycle Produces Four-Carbon Compounds from Acetate 657 The Citric Acid and Glyoxylate Cycles Are Coordinately Regulated 658 17 Fatty Acid Catabolism 667 17.1 Digestion, Mobilization, and Transport of Fats 668 Dietary Fats Are Absorbed in the Small Intestine 668 Hormones Trigger Mobilization of Stored Triacylglycerols 669 Fatty Acids Are Activated and Transported into Mitochondria 670 17.2 Oxidation of Fatty Acids 672 The Oxidation of Saturated Fatty Acids Has Four Basic Steps 673 The Four -Oxidation Steps Are Repeated to Yield Acetyl-CoA and ATP 674 Acetyl-CoA Can Be Further Oxidized in the Citric Acid Cycle 675 BOX 17–1 Fat Bears Carry Out Oxidation in Their Sleep 676 Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactions 677 Complete Oxidation of Odd-Number Fatty Acids Requires Three Extra Reactions 677 Fatty Acid Oxidation Is Tightly Regulated 678 Transcription Factors Turn on the Synthesis of Proteins for Lipid Catabolism 679 BOX 17–2 Coenzyme B12: A Radical Solution to a Perplexing Problem 680 Genetic Defects in Fatty Acyl–CoA Dehydrogenases Cause Serious Disease 682 Peroxisomes Also Carry Out Oxidation 682 Plant Peroxisomes and Glyoxysomes Use Acetyl-CoA from Oxidation as a Biosynthetic Precursor 683 The -Oxidation Enzymes of Different Organelles Have Diverged during Evolution 683 The Oxidation of Fatty Acids Occurs in the Endoplasmic Reticulum 684 Phytanic Acid Undergoes Oxidation in Peroxisomes 685 17.3 Ketone Bodies 686 Ketone Bodies, Formed in the Liver, Are Exported to Other Organs as Fuel 686 Ketone Bodies Are Overproduced in Diabetes and during Starvation 688 18 Amino Acid Oxidation and the Production of Urea 695 18.1 Metabolic Fates of Amino Groups 696 Dietary Protein Is Enzymatically Degraded to Amino Acids 697 Pyridoxal Phosphate Participates in the Transfer of -Amino Groups to -Ketoglutarate 699 Glutamate Releases Its Amino Group As Ammonia in the Liver 700 Glutamine Transports Ammonia in the Bloodstream 702 Alanine Transports Ammonia from Skeletal Muscles to the Liver 703 Ammonia Is Toxic to Animals 703 18.2 Nitrogen Excretion and the Urea Cycle 704 Urea Is Produced from Ammonia in Five Enzymatic Steps 704 The Citric Acid and Urea Cycles Can Be Linked 706 The Activity of the Urea Cycle Is Regulated at Two Levels 708 Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis 708 BOX 18–1 MEDICINE: Assays for Tissue Damage 708 Genetic Defects in the Urea Cycle Can Be LifeThreatening 709 18.3 Pathways of Amino Acid Degradation 710 Some Amino Acids Are Converted to Glucose, Others to Ketone Bodies 711 Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism 712 Contents xxiii FMTOC.indd Page xxiii 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop
xxiv Contents l-CoA 760 tabolism Is Genetically Defectiv ATP-Pr ducing Pathways Are Coordinately Five Amino Acids Are Convertedta-Ketogtara 761 19.4 Mitochondria in Thermogenesis,Steroid Synthesis,and Apoptosis 762 2MEDICIwEsaentifcsSieuths5oWe& 723 ia in Brown Adipose 762 Murder Musten al P-450 Oxygenases Catalyze spartate Are Degraded to 763 724 Mitochondria Are Central to the Initiation of 764 19 Oxidative Phosphorylation and 19.5 Mitochondrial Genes:Their Origin and Photophosphorylation 731 the Effects of Mutations 可 OXIDATIVE PHOSPHORYLATION 732 Mitochondria Evolved from Endosymbiotic Mutations 765 19.1 Electron-Transfer Reactions in Mitochondria 732 ndrial DNA Accumulate Electrons Are Funneled to Univ ersal electron Som out the 766 througha Series of 767 Bound Carrier 735 Dise from Dofoets in the Mitochondria of Pancreatic Cells 76s Mit r Complexes May Associae i 37 PHOTOSYNTHESIS:HARVESTING LIGHT ENERGY 769 73 769 The ergy of e 19.6 General Features of Photophosphorylation 743 Reactive Oxy Are ge erated during Chlo B0X19-1 Ho Stinking Plants and Alternative 19.7 Light Absorotion 771 Respiratory Pathway sorb Light Energy for Plar ror NADH eAlternative Mechanisms Photo 771 ats Extend the Range of Light 19.2 ATP Synthesis 747 773 ATP Synt ase Has Two Functional Domains. ized Relative to ADP on the 19.8 The Central Photochemical Event:Light-Driven 776 Bact e One of Two s of Single nte OL AT se Can Assum Three DifferentC ion of ene Ro e Binding-Change Mechanism for ATP 752 with ugh the F。Complex 781 Complex Links Photos and I 782 ATP 755 ed the ETHODS:At rce Microscopy to 756 of ATp Rel on of LHCII The Proton-Motive Force Active between the Two Pho 757 Water Is Split by the Oxygen-Evolving Complex 19.9 ATP Synthesis by Photophosphorylation 786 A Proton Gradient Couples Electron Flow and 759 786 etry of 760 787 during Hypoxia vents ATP Hydrolysis The 760 787
Six Amino Acids Are Degraded to Pyruvate 715 Seven Amino Acids Are Degraded to Acetyl-CoA 717 Phenylalanine Catabolism Is Genetically Defective in Some People 719 Five Amino Acids Are Converted to -Ketoglutarate 721 Four Amino Acids Are Converted to Succinyl-CoA 722 Branched-Chain Amino Acids Are Not Degraded in the Liver 723 BOX 18–2 MEDICINE: Scientific Sleuths Solve a Murder Mystery 724 Asparagine and Aspartate Are Degraded to Oxaloacetate 724 19 Oxidative Phosphorylation and Photophosphorylation 731 OXIDATIVE PHOSPHORYLATION 732 19.1 Electron-Transfer Reactions in Mitochondria 732 Electrons Are Funneled to Universal Electron Acceptors 734 Electrons Pass through a Series of MembraneBound Carriers 735 Electron Carriers Function in Multienzyme Complexes 737 Mitochondrial Complexes May Associate in Respirasomes 743 The Energy of Electron Transfer Is Efficiently Conserved in a Proton Gradient 743 Reactive Oxygen Species Are Generated during Oxidative Phosphorylation 745 BOX 19–1 Hot, Stinking Plants and Alternative Respiratory Pathways 746 Plant Mitochondria Have Alternative Mechanisms for Oxidizing NADH 746 19.2 ATP Synthesis 747 ATP Synthase Has Two Functional Domains, Fo and F1 750 ATP Is Stabilized Relative to ADP on the Surface of F1 750 The Proton Gradient Drives the Release of ATP from the Enzyme Surface 751 Each Subunit of ATP Synthase Can Assume Three Different Conformations 752 Rotational Catalysis Is Key to the Binding-Change Mechanism for ATP Synthesis 752 How Does Proton Flow through the Fo Complex Produce Rotary Motion? 755 Chemiosmotic Coupling Allows Nonintegral Stoichiometries of O2 Consumption and ATP Synthesis 755 BOX 19–2 METHODS: Atomic Force Microscopy to Visualize Membrane Proteins 756 The Proton-Motive Force Energizes Active Transport 757 Shuttle Systems Indirectly Convey Cytosolic NADH into Mitochondria for Oxidation 758 19.3 Regulation of Oxidative Phosphorylation 759 Oxidative Phosphorylation Is Regulated by Cellular Energy Needs 760 An Inhibitory Protein Prevents ATP Hydrolysis during Hypoxia 760 Hypoxia Leads to ROS Production and Several Adaptive Responses 760 ATP-Producing Pathways Are Coordinately Regulated 761 19.4 Mitochondria in Thermogenesis, Steroid Synthesis, and Apoptosis 762 Uncoupled Mitochondria in Brown Adipose Tissue Produce Heat 762 Mitochondrial P-450 Oxygenases Catalyze Steroid Hydroxylations 763 Mitochondria Are Central to the Initiation of Apoptosis 764 19.5 Mitochondrial Genes: Their Origin and the Effects of Mutations 765 Mitochondria Evolved from Endosymbiotic Bacteria 765 Mutations in Mitochondrial DNA Accumulate throughout the Life of the Organism 766 Some Mutations in Mitochondrial Genomes Cause Disease 767 Diabetes Can Result from Defects in the Mitochondria of Pancreatic Cells 768 PHOTOSYNTHESIS: HARVESTING LIGHT ENERGY 769 19.6 General Features of Photophosphorylation 769 Photosynthesis in Plants Takes Place in Chloroplasts 769 Light Drives Electron Flow in Chloroplasts 770 19.7 Light Absorption 771 Chlorophylls Absorb Light Energy for Photosynthesis 771 Accessory Pigments Extend the Range of Light Absorption 773 Chlorophyll Funnels the Absorbed Energy to Reaction Centers by Exciton Transfer 774 19.8 The Central Photochemical Event: Light-Driven Electron Flow 776 Bacteria Have One of Two Types of Single Photochemical Reaction Center 776 Kinetic and Thermodynamic Factors Prevent the Dissipation of Energy by Internal Conversion 778 In Plants, Two Reaction Centers Act in Tandem 779 Antenna Chlorophylls Are Tightly Integrated with Electron Carriers 781 The Cytochrome b6 f Complex Links Photosystems II and I 782 Cyclic Electron Flow between PSI and the Cytochrome b6 f Complex Increases the Production of ATP Relative to NADPH 783 State Transitions Change the Distribution of LHCII between the Two Photosystems 783 Water Is Split by the Oxygen-Evolving Complex 784 19.9 ATP Synthesis by Photophosphorylation 786 A Proton Gradient Couples Electron Flow and Phosphorylation 786 The Approximate Stoichiometry of Photophosphorylation Has Been Established 787 The ATP Synthase of Chloroplasts Is Like That of Mitochondria 787 xxiv Contents FMTOC.indd Page xxiv 09/10/12 1:57 PM user-F408 /Users/user-F408/Desktop