My Years with General Motors

About this Book Cover Page Halftitle Page Title Page Copyright Dedication About the Authors A Note on the Nature of Science Overview of key features Tools and Resources to Support Teaching Acknowledgments Contents in Brief Contents Chapter 1 The Foundations of Biochemistry 1.1 Cellular Foundations Cells Are the Structural and Functional Units of All Living Organisms Cellular Dimensions Are Limited by Diffusion Organisms Belong to Three Distinct Domains of Life Organisms Differ Widely in Their Sources of Energy and Biosynthetic Precursors Bacterial and Archaeal Cells Share Common Features but Differ in Important Ways Eukaryotic Cells Have a Variety of Membranous Organelles, Which Can Be Isolated for Study The Cytoplasm Is Organized by the Cytoskeleton and Is Highly Dynamic Cells Build Supramolecular Structures In Vitro Studies May Overlook Important Interactions among Molecules 1.2 Chemical Foundations Biomolecules Are Compounds of Carbon with a Variety of Functional Groups Cells Contain a Universal Set of Small Molecules Macromolecules Are the Major Constituents of Cells Three-Dimensional Structure Is Described by Configuration and Conformation Interactions between Biomolecules Are Stereospecific 1.3 Physical Foundations Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their Surroundings Organisms Transform Energy and Matter from Their Surroundings Creating and Maintaining Order Requires Work and Energy Energy Coupling Links Reactions in Biology K[eq] and ΔG° Are Measures of a Reaction’s Tendency to Proceed Spontaneously Enzymes Promote Sequences of Chemical Reactions Metabolism Is Regulated to Achieve Balance and Economy 1.4 Genetic Foundations Genetic Continuity Is Vested in Single DNA Molecules The Structure of DNA Allows Its Replication and Repair with Near-Perfect Fidelity The Linear Sequence in DNA Encodes Proteins with Three-Dimensional Structures 1.5 Evolutionary Foundations Changes in the Hereditary Instructions Allow Evolution Biomolecules First Arose by Chemical Evolution RNA or Related Precursors May Have Been the First Genes and Catalysts Biological Evolution Began More Than Three and a Half Billion Years Ago The First Cell Probably Used Inorganic Fuels Eukaryotic Cells Evolved from Simpler Precursors in Several Stages Molecular Anatomy Reveals Evolutionary Relationships Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes Genomic Comparisons Have Increasing Importance in Medicine Chapter Review Key Terms Problems Part I Structure and Catalysis Chapter 2 Water, The Solvent of Life 2.1 Weak Interactions in Aqueous Systems Hydrogen Bonding Gives Water Its Unusual Properties Water Forms Hydrogen Bonds with Polar Solutes Water Interacts Electrostatically with Charged Solutes Nonpolar Gases Are Poorly Soluble in Water Nonpolar Compounds Force Energetically Unfavorable Changes in the Structure of Water van der Waals Interactions Are Weak Interatomic Attractions Weak Interactions Are Crucial to Macromolecular Structure and Function Concentrated Solutes Produce Osmotic Pressure 2.2 Ionization of Water, Weak Acids, and Weak Bases Pure Water Is Slightly Ionized The Ionization of Water Is Expressed by an Equilibrium Constant The pH Scale Designates the H[+] and H[−] Concentrations Weak Acids and Bases Have Characteristic Acid Dissociation Constants Titration Curves Reveal the p[Ka] of Weak Acids 2.3 Buffering against pH Changes in Biological Systems Buffers Are Mixtures of Weak Acids and Their Conjugate Bases The Henderson-Hasselbalch Equation Relates pH, p[Ka], and Buffer Concentration Weak Acids or Bases Buffer Cells and Tissues against pH Changes Untreated Diabetes Produces Life-Threatening Acidosis Chapter Review Key Terms Problems Chapter 3 Amino Acids, Peptides, and Proteins 3.1 Amino Acids Amino Acids Share Common Structural Features The Amino Acid Residues in Proteins Are L Stereoisomers Amino Acids Can Be Classified by R Group Uncommon Amino Acids Also Have Important Functions Amino Acids Can Act as Acids and Bases Amino Acids Differ in Their Acid-Base Properties 3.2 Peptides and Proteins Peptides Are Chains of Amino Acids Peptides Can Be Distinguished by Their Ionization Behavior Biologically Active Peptides and Polypeptides Occur in a Vast Range of Sizes and Compositions Some Proteins Contain Chemical Groups Other Than Amino Acids 3.3 Working with Proteins Proteins Can Be Separated and Purified Proteins Can Be Separated and Characterized by Electrophoresis Unseparated Proteins Are Detected and Quantified Based on Their Functions 3.4 The Structure of Proteins: Primary Structure The Function of a Protein Depends on Its Amino Acid Sequence Protein Structure Is Studied Using Methods That Exploit Protein Chemistry Mass Spectrometry Provides Information on Molecular Mass, Amino Acid Sequence, and Entire Proteomes Small Peptides and Proteins Can Be Chemically Synthesized Amino Acid Sequences Provide Important Biochemical Information Protein Sequences Help Elucidate the History of Life on Earth Chapter Review Key Terms Problems Chapter 4 The Three-Dimensional Structure of Proteins 4.1 Overview of Protein Structure A Protein’s Conformation Is Stabilized Largely by Weak Interactions Packing of Hydrophobic Amino Acids Away from Water Favors Protein Folding Polar Groups Contribute Hydrogen Bonds and Ion Pairs to Protein Folding Individual van der Waals Interactions Are Weak but Combine to Promote Folding The Peptide Bond Is Rigid and Planar 4.2 Protein Secondary Structure The α Helix Is a Common Protein Secondary Structure Amino Acid Sequence Affects Stability of the α Helix The β Conformation Organizes Polypeptide Chains into Sheets β Turns Are Common in Proteins Common Secondary Structures Have Characteristic Dihedral Angles Common Secondary Structures Can Be Assessed by Circular Dichroism 4.3 Protein Tertiary and Quaternary Structures Fibrous Proteins Are Adapted for a Structural Function Structural Diversity Reflects Functional Diversity in Globular Proteins Myoglobin Provided Early Clues about the Complexity of Globular Protein Structure Globular Proteins Have a Variety of Tertiary Structures Some Proteins or Protein Segments Are Intrinsically Disordered Protein Motifs Are the Basis for Protein Structural Classification Protein Quaternary Structures Range from Simple Dimers to Large Complexes 4.4 Protein Denaturation and Folding Loss of Protein Structure Results in Loss of Function Amino Acid Sequence Determines Tertiary Structure Polypeptides Fold Rapidly by a Stepwise Process Some Proteins Undergo Assisted Folding Defects in Protein Folding Are the Molecular Basis for Many Human Genetic Disorders 4.5 Determination of Protein and Biomolecular Structures X-ray Diffraction Produces Electron Density Maps from Protein Crystals Distances between Protein Atoms Can Be Measured by Nuclear Magnetic Resonance Thousands of Individual Molecules Are Used to Determine Structures by Cryo-Electron Microscopy Chapter Review Key Terms Problems Chapter 5 Protein Function 5.1 Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins Oxygen Can Bind to a Heme Prosthetic Group Globins Are a Family of Oxygen-Binding Proteins Myoglobin Has a Single Binding Site for Oxygen Protein-Ligand Interactions Can Be Described Quantitatively Protein Structure Affects How Ligands Bind Hemoglobin Transports Oxygen in Blood Hemoglobin Subunits Are Structurally Similar to Myoglobin Hemoglobin Undergoes a Structural Change on Binding Oxygen Hemoglobin Binds Oxygen Cooperatively Cooperative Ligand Binding Can Be Described Quantitatively Two Models Suggest Mechanisms for Cooperative Binding Hemoglobin Also Transports H[+] and CO[2] Oxygen Binding to Hemoglobin Is Regulated by 2,3-Bisphosphoglycerate Sickle Cell Anemia Is a Molecular Disease of Hemoglobin 5.2 Complementary Interactions between Proteins and Ligands: The Immune System and Immunoglobulins The Immune Response Includes a Specialized Array of Cells and Proteins Antibodies Have Two Identical Antigen-Binding Sites Antibodies Bind Tightly and Specifically to Antigen The Antibody-Antigen Interaction Is the Basis for a Variety of Important Analytical Procedures 5.3 Protein Interactions Modulated by Chemical Energy: Actin, Myosin, and Molecular Motors The Major Proteins of Muscle Are Myosin and Actin Additional Proteins Organize the Thin and Thick Filaments into Ordered Structures Myosin Thick Filaments Slide along Actin Thin Filaments Chapter Review Key Terms Problems Chapter 6 Enzymes 6.1 An Introduction to Enzymes Most Enzymes Are Proteins Enzymes Are Classified by the Reactions They Catalyze 6.2 How Enzymes Work Enzymes Affect Reaction Rates, Not Equilibria Reaction Rates and Equilibria Have Precise Thermodynamic Definitions A Few Principles Explain the Catalytic Power and Specificity of Enzymes Noncovalent Interactions between Enzyme and Substrate Are Optimized in the Transition State Covalent Interactions and Metal Ions Contribute to Catalysis 6.3 Enzyme Kinetics as an Approach to Understanding Mechanism Substrate Concentration Affects the Rate of Enzyme-Catalyzed Reactions The Relationship between Substrate Concentration and Reaction Rate Can Be Expressed with the Michaelis-Menten Equation Michaelis-Menten Kinetics Can Be Analyzed Quantitatively Kinetic Parameters Are Used to Compare Enzyme Activities Many Enzymes Catalyze Reactions with Two or More Substrates Enzyme Activity Depends on pH Pre–Steady State Kinetics Can Provide Evidence for Specific Reaction Steps Enzymes Are Subject to Reversible or Irreversible Inhibition 6.4 Examples of Enzymatic Reactions The Chymotrypsin Mechanism Involves Acylation and Deacylation of a Ser Residue An Understanding of Protease Mechanisms Leads to New Treatments for HIV Infection Hexokinase Undergoes Induced Fit on Substrate Binding The Enolase Reaction Mechanism Requires Metal Ions An Understanding of Enzyme Mechanism Produces Useful Antibiotics 6.5 Regulatory Enzymes Allosteric Enzymes Undergo Conformational Changes in Response to Modulator Binding The Kinetic Properties of Allosteric Enzymes Diverge from Michaelis-Menten Behavior Some Enzymes Are Regulated by Reversible Covalent Modification Phosphoryl Groups Affect the Structure and Catalytic Activity of Enzymes Multiple Phosphorylations Allow Exquisite Regulatory Control Some Enzymes and Other Proteins Are Regulated by Proteolytic Cleavage of an Enzyme Precursor A Cascade of Proteolytically Activated Zymogens Leads to Blood Coagulation Some Regulatory Enzymes Use Several Regulatory Mechanisms Chapter Review Key Terms Problems Chapter 7 Carbohydrates and Glycobiology 7.1 Monosaccharides and Disaccharides The Two Families of Monosaccharides Are Aldoses and Ketoses Monosaccharides Have Asymmetric Centers The Common Monosaccharides Have Cyclic Structures Organisms Contain a Variety of Hexose Derivatives Sugars That Are, or Can Form, Aldehydes Are Reducing Sugars 7.2 Polysaccharides Some Homopolysaccharides Are Storage Forms of Fuel Some Homopolysaccharides Serve Structural Roles Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding Peptidoglycan Reinforces the Bacterial Cell Wall Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, and Glycolipids Proteoglycans Are Glycosaminoglycan-Containing Macromolecules of the Cell Surface and Extracellular Matrix Glycoproteins Have Covalently Attached Oligosaccharides Glycolipids and Lipopolysaccharides Are Membrane Components 7.4 Carbohydrates as Informational Molecules: The Sugar Code Oligosaccharide Structures Are Information-Dense Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes Lectin-Carbohydrate Interactions Are Highly Specific and Often Multivalent 7.5 Working with Carbohydrates Chapter Review Key Terms Problems Chapter 8 Nucleotides and Nucleic Acids 8.1 Some Basic Definitions and Conventions Nucleotides and Nucleic Acids Have Characteristic Bases and Pentoses Phosphodiester Bonds Link Successive Nucleotides in Nucleic Acids The Properties of Nucleotide Bases Affect the Three-Dimensional Structure of Nucleic Acids 8.2 Nucleic Acid Structure DNA Is a Double Helix That Stores Genetic Information DNA Can Occur in Different Three-Dimensional Forms Certain DNA Sequences Adopt Unusual Structures Messenger RNAs Code for Polypeptide Chains Many RNAs Have More Complex Three-Dimensional Structures 8.3 Nucleic Acid Chemistry Double-Helical DNA and RNA Can Be Denatured Nucleotides and Nucleic Acids Undergo Nonenzymatic Transformations Some Bases of DNA Are Methylated The Chemical Synthesis of DNA Has Been Automated Gene Sequences Can Be Amplified with the Polymerase Chain Reaction The Sequences of Long DNA Strands Can Be Determined DNA Sequencing Technologies Are Advancing Rapidly 8.4 Other Functions of Nucleotides Nucleotides Carry Chemical Energy in Cells Adenine Nucleotides Are Components of Many Enzyme Cofactors Some Nucleotides Are Regulatory Molecules Adenine Nucleotides Also Serve as Signals Chapter Review Key Terms Problems Chapter 9 DNA-Based Information Technologies 9.1 Studying Genes and Their Products Genes Can Be Isolated by DNA Cloning Restriction Endonucleases and DNA Ligases Yield Recombinant DNA Cloning Vectors Allow Amplification of Inserted DNA Segments Cloned Genes Can Be Expressed to Amplify Protein Production Many Different Systems Are Used to Express Recombinant Proteins Alteration of Cloned Genes Produces Altered Proteins Terminal Tags Provide Handles for Affinity Purification The Polymerase Chain Reaction Offers Many Options for Cloning Experiments DNA Libraries Are Specialized Catalogs of Genetic Information 9.2 Exploring Protein Function on the Scale of Cells or Whole Organisms Sequence or Structural Relationships Can Suggest Protein Function When and Where a Protein Is Present in a Cell Can Suggest Protein Function Knowing What a Protein Interacts with Can Suggest Its Function The Effect of Deleting or Altering a Protein Can Suggest Its Function Many Proteins Are Still Undiscovered 9.3 Genomics and the Human Story The Human Genome Contains Many Types of Sequences Genome Sequencing Informs Us about Our Humanity Genome Comparisons Help Locate Genes Involved in Disease Genome Sequences Inform Us about Our Past and Provide Opportunities for the Future Chapter Review Key Terms Problems Chapter 10 Lipids 10.1 Storage Lipids Fatty Acids Are Hydrocarbon Derivatives Triacylglycerols Are Fatty Acid Esters of Glycerol Triacylglycerols Provide Stored Energy and Insulation Partial Hydrogenation of Cooking Oils Improves Their Stability but Creates Fatty Acids with Harmful Health Effects Waxes Serve as Energy Stores and Water Repellents 10.2 Structural Lipids in Membranes Glycerophospholipids Are Derivatives of Phosphatidic Acid Some Glycerophospholipids Have Ether-Linked Fatty Acids Galactolipids of Plants and Ether-Linked Lipids of Archaea Are Environmental Adaptations Sphingolipids Are Derivatives of Sphingosine Sphingolipids at Cell Surfaces Are Sites of Biological Recognition Phospholipids and Sphingolipids Are Degraded in Lysosomes Sterols Have Four Fused Carbon Rings 10.3 Lipids as Signals, Cofactors, and Pigments Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular Signals Eicosanoids Carry Messages to Nearby Cells Steroid Hormones Carry Messages between Tissues Vascular Plants Produce Thousands of Volatile Signals Vitamins A and D Are Hormone Precursors Vitamins E and K and the Lipid Quinones Are Oxidation-Reduction Cofactors Dolichols Activate Sugar Precursors for Biosynthesis Many Natural Pigments Are Lipidic Conjugated Dienes Polyketides Are Natural Products with Potent Biological Activities 10.4 Working with Lipids Lipid Extraction Requires Organic Solvents Adsorption Chromatography Separates Lipids of Different Polarity Gas Chromatography Resolves Mixtures of Volatile Lipid Derivatives Specific Hydrolysis Aids in Determination of Lipid Structure Mass Spectrometry Reveals Complete Lipid Structure Lipidomics Seeks to Catalog All Lipids and Their Functions Chapter Review Key Terms Problems Chapter 11 Biological Membranes and Transport 11.1 The Composition and Architecture of Membranes The Lipid Bilayer Is Stable in Water Bilayer Architecture Underlies the Structure and Function of Biological Membranes The Endomembrane System Is Dynamic and Functionally Differentiated Membrane Proteins Are Receptors, Transporters, and Enzymes Membrane Proteins Differ in the Nature of Their Association with the Membrane Bilayer The Topology of an Integral Membrane Protein Can Often Be Predicted from Its Sequence Covalently Attached Lipids Anchor or Direct Some Membrane Proteins 11.2 Membrane Dynamics Acyl Groups in the Bilayer Interior Are Ordered to Varying Degrees Transbilayer Movement of Lipids Requires Catalysis Lipids and Proteins Diffuse Laterally in the Bilayer Sphingolipids and Cholesterol Cluster Together in Membrane Rafts Membrane Curvature and Fusion Are Central to Many Biological Processes Integral Proteins of the Plasma Membrane Are Involved in Surface Adhesion, Signaling, and Other Cellular Processes 11.3 Solute Transport across Membranes Transport May Be Passive or Active Transporters and Ion Channels Share Some Structural Properties but Have Different Mechanisms The Glucose Transporter of Erythrocytes Mediates Passive Transport The Chloride-Bicarbonate Exchanger Catalyzes Electroneutral Cotransport of Anions across the Plasma Membrane Active Transport Results in Solute Movement against a Concentration or Electrochemical Gradient P-Type ATPases Undergo Phosphorylation during Their Catalytic Cycles V-Type and F-Type ATPases Are ATP-Driven Proton Pumps ABC Transporters Use ATP to Drive the Active Transport of a Wide Variety of Substrates Ion Gradients Provide the Energy for Secondary Active Transport Aquaporins Form Hydrophilic Transmembrane Channels for the Passage of Water Ion-Selective Channels Allow Rapid Movement of Ions across Membranes The Structure of a K[+] Channel Reveals the Basis for Its Specificity Chapter Review Key Terms Problems Chapter 12 Biochemical Signaling 12.1 General Features of Signal Transduction Signal-Transducing Systems Share Common Features The General Process of Signal Transduction in Animals Is Universal 12.2 G Protein–Coupled Receptors and Second Messengers The β-Adrenergic Receptor System Acts through the Second Messenger cAMP Cyclic AMP Activates Protein Kinase A Several Mechanisms Cause Termination of the β-Adrenergic Response The β-Adrenergic Receptor Is Desensitized by Phosphorylation and by Association with Arrestin Cyclic AMP Acts as a Second Messenger for Many Regulatory Molecules G Proteins Act as Self-Limiting Switches in Many Processes Diacylglycerol, Inositol Trisphosphate, and Ca2+ Have Related Roles as Second Messengers Calcium Is a Second Messenger That Is Limited in Space and Time 12.3 GPCRs in Vision, Olfaction, and Gustation The Vertebrate Eye Uses Classic GPCR Mechanisms Vertebrate Olfaction and Gustation Use Mechanisms Similar to the Visual System All GPCR Systems Share Universal Features 12.4 Receptor Tyrosine Kinases Stimulation of the Insulin Receptor Initiates a Cascade of Protein Phosphorylation Reactions The Membrane Phospholipid PIP3 Functions at a Branch in Insulin Signaling Cross Talk among Signaling Systems Is Common and Complex 12.5 Multivalent Adaptor Proteins and Membrane Rafts Protein Modules Bind Phosphorylated Tyr, Ser, or Thr Residues in Partner Proteins Membrane Rafts and Caveolae Segregate Signaling Proteins 12.6 Gated Ion Channels Ion Channels Underlie Rapid Electrical Signaling in Excitable Cells Voltage-Gated Ion Channels Produce Neuronal Action Potentials Neurons Have Receptor Channels That Respond to Different Neurotransmitters Toxins Target Ion Channels 12.7 Regulation of Transcription by Nuclear Hormone Receptors 12.8 Regulation of the Cell Cycle by Protein Kinases The Cell Cycle Has Four Stages Levels of Cyclin-Dependent Protein Kinases Oscillate CDKs Are Regulated by Phosphorylation, Cyclin Degradation, Growth Factors, and Specific Inhibitors CDKs Regulate Cell Division by Phosphorylating Critical Proteins 12.9 Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death Oncogenes Are Mutant Forms of the Genes for Proteins That Regulate the Cell Cycle Defects in Certain Genes Remove Normal Restraints on Cell Division Apoptosis Is Programmed Cell Suicide Chapter Review Key Terms Problems Part II Bioenergetics and Metabolism Chapter 13 Introduction to Metabolism 13.1 Bioenergetics and Thermodynamics Biological Energy Transformations Obey the Laws of Thermodynamics Standard Free-Energy Change Is Directly Related to the Equilibrium Constant Actual Free-Energy Changes Depend on Reactant and Product Concentrations Standard Free-Energy Changes Are Additive 13.2 Chemical Logic and Common Biochemical Reactions Biochemical Reactions Occur in Repeating Patterns Biochemical and Chemical Equations Are Not Identical 13.3 Phosphoryl Group Transfers and ATP The Free-Energy Change for ATP Hydrolysis Is Large and Negative Other Phosphorylated Compounds and Thioesters Also Have Large, Negative Free Energies of Hydrolysis ATP Provides Energy by Group Transfers, Not by Simple Hydrolysis ATP Donates Phosphoryl, Pyrophosphoryl, and Adenylyl Groups Assembly of Informational Macromolecules Requires Energy Transphosphorylations between Nucleotides Occur in All Cell Types 13.4 Biological Oxidation-Reduction Reactions The Flow of Electrons Can Do Biological Work Oxidation-Reductions Can Be Described as Half-Reactions Biological Oxidations Often Involve Dehydrogenation Reduction Potentials Measure Affinity for Electrons Standard Reduction Potentials Can Be Used to Calculate Free-Energy Change A Few Types of Coenzymes and Proteins Serve as Universal Electron Carriers NAD Has Important Functions in Addition to Electron Transfer Flavin Nucleotides Are Tightly Bound in Flavoproteins 13.5 Regulation of Metabolic Pathways Cells and Organisms Maintain a Dynamic Steady State Both the Amount and the Catalytic Activity of an Enzyme Can Be Regulated Reactions Far from Equilibrium in Cells Are Common Points of Regulation Adenine Nucleotides Play Special Roles in Metabolic Regulation Chapter Review Key Terms Problems Chapter 14 Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway 14.1 Glycolysis An Overview: Glycolysis Has Two Phases The Preparatory Phase of Glycolysis Requires ATP The Payoff Phase of Glycolysis Yields ATP and NADH The Overall Balance Sheet Shows a Net Gain of Two ATP and Two NADH Per Glucose 14.2 Feeder Pathways for Glycolysis Endogenous Glycogen and Starch Are Degraded by Phosphorolysis Dietary Polysaccharides and Disaccharides Undergo Hydrolysis to Monosaccharides 14.3 Fates of Pyruvate The Pasteur and Warburg Effects Are Due to Dependence on Glycolysis Alone for ATP Production Pyruvate Is the Terminal Electron Acceptor in Lactic Acid Fermentation Ethanol Is the Reduced Product in Ethanol Fermentation Fermentations Produce Some Common Foods and Industrial Chemicals 14.4 Gluconeogenesis The First Bypass: Conversion of Pyruvate to Phosphoenolpyruvate Requires Two Exergonic Reactions The Second and Third Bypasses Are Simple Dephosphorylations by Phosphatases Gluconeogenesis Is Energetically Expensive, But Essential Mammals Cannot Convert Fatty Acids to Glucose; Plants and Microorganisms Can 14.5 Coordinated Regulation of Glycolysis and Gluconeogenesis Hexokinase Isozymes Are Affected Differently by Their Product, Glucose 6-Phosphate Phosphofructokinase-1 and Fructose 1,6-Bisphosphatase Are Reciprocally Regulated Fructose 2,6-Bisphosphate Is a Potent Allosteric Regulator of PFK-1 and FBPase-1 Xylulose 5-Phosphate Is a Key Regulator of Carbohydrate and Fat Metabolism The Glycolytic Enzyme Pyruvate Kinase Is Allosterically Inhibited by ATP Conversion of Pyruvate to Phosphoenolpyruvate Is Stimulated When Fatty Acids Are Available Transcriptional Regulation Changes the Number of Enzyme Molecules 14.6 Pentose Phosphate Pathway of Glucose Oxidation The Oxidative Phase Produces NADPH and Pentose Phosphates The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate Glucose 6-Phosphate Is Partitioned between Glycolysis and the Pentose Phosphate Pathway Thiamine Deficiency Causes Beriberi and Wernicke-Korsakoff Syndrome Chapter Review Key Terms Problems Chapter 15 The Metabolism of Glycogen in Animals 15.1 The Structure and Function of Glycogen Vertebrate Animals Require a Ready Fuel Source for Brain and Muscle Glycogen Granules Have Many Tiers of Branched Chains of d-Glucose 15.2 Breakdown and Synthesis of Glycogen Glycogen Breakdown Is Catalyzed by Glycogen Phosphorylase Glucose 1-Phosphate Can Enter Glycolysis or, in Liver, Replenish Blood Glucose The Sugar Nucleotide UDP-Glucose Donates Glucose for Glycogen Synthesis Glycogenin Primes the Initial Sugar Residues in Glycogen 15.3 Coordinated Regulation of Glycogen Breakdown and Synthesis Glycogen Phosphorylase Is Regulated by Hormone-Stimulated Phosphorylation and by Allosteric Effectors Glycogen Synthase Also Is Subject to Multiple Levels of Regulation Allosteric and Hormonal Signals Coordinate Carbohydrate Metabolism Globally Carbohydrate and Lipid Metabolism Are Integrated by Hormonal and Allosteric Mechanisms Chapter Review Key Terms Problems Chapter 16 The Citric Acid Cycle 16.1 Production of Acetyl-CoA (Activated Acetate) Pyruvate Is Oxidized to Acetyl-CoA and CO2 The PDH Complex Employs Three Enzymes and Five Coenzymes to Oxidize Pyruvate The PDH Complex Channels Its Intermediates through Five Reactions 16.2 Reactions of the Citric Acid Cycle The Sequence of Reactions in the Citric Acid Cycle Makes Chemical Sense The Citric Acid Cycle Has Eight Steps The Energy of Oxidations in the Cycle Is Efficiently Conserved 16.3 The Hub of Intermediary Metabolism The Citric Acid Cycle Serves in Both Catabolic and Anabolic Processes Anaplerotic Reactions Replenish Citric Acid Cycle Intermediates Biotin in Pyruvate Carboxylase Carries One-Carbon (CO2) Groups 16.4 Regulation of the Citric Acid Cycle Production of Acetyl-CoA by the PDH Complex Is Regulated by Allosteric and Covalent Mechanisms The Citric Acid Cycle Is Also Regulated at Three Exergonic Steps Citric Acid Cycle Activity Changes in Tumors Certain Intermediates Are Channeled through Metabolons Chapter Review Key Terms Problems Chapter 17 Fatty Acid Catabolism 17.1 Digestion, Mobilization, and Transport of Fats Dietary Fats Are Absorbed in the Small Intestine Hormones Trigger Mobilization of Stored Triacylglycerols Fatty Acids Are Activated and Transported into Mitochondria 17.2 Oxidation of Fatty Acids The β Oxidation of Saturated Fatty Acids Has Four Basic Steps The Four β-Oxidation Steps Are Repeated to Yield Acetyl-CoA and ATP Acetyl-CoA Can Be Further Oxidized in the Citric Acid Cycle Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactions Complete Oxidation of Odd-Number Fatty Acids Requires Three Extra Reactions Fatty Acid Oxidation Is Tightly Regulated Transcription Factors Turn on the Synthesis of Proteins for Lipid Catabolism Genetic Defects in Fatty Acyl–CoA Dehydrogenases Cause Serious Disease Peroxisomes Also Carry Out β Oxidation Phytanic Acid Undergoes α Oxidation in Peroxisomes 17.3 Ketone Bodies Ketone Bodies, Formed in the Liver, Are Exported to Other Organs as Fuel Ketone Bodies Are Overproduced in Diabetes and during Starvation Chapter Review Key Terms Problems Chapter 18 Amino Acid Oxidation and the Production of Urea 18.1 Metabolic Fates of Amino Groups Dietary Protein Is Enzymatically Degraded to Amino Acids Pyridoxal Phosphate Participates in the Transfer of α-Amino Groups to α-Ketoglutarate Glutamate Releases Its Amino Group as Ammonia in the Liver Glutamine Transports Ammonia in the Bloodstream Alanine Transports Ammonia from Skeletal Muscles to the Liver Ammonia Is Toxic to Animals 18.2 Nitrogen Excretion and the Urea Cycle Urea Is Produced from Ammonia in Five Enzymatic Steps The Citric Acid and Urea Cycles Can Be Linked The Activity of the Urea Cycle Is Regulated at Two Levels Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis Genetic Defects in the Urea Cycle Can Be Life-Threatening 18.3 Pathways of Amino Acid Degradation Some Amino Acids Can Contribute to Gluconeogenesis, Others to Ketone Body Formation Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism Six Amino Acids Are Degraded to Pyruvate Seven Amino Acids Are Degraded to Acetyl-CoA Phenylalanine Catabolism Is Genetically Defective in Some People Five Amino Acids Are Converted to -Ketoglutarate Four Amino Acids Are Converted to Succinyl-CoA Branched-Chain Amino Acids Are Not Degraded in the Liver Asparagine and Aspartate Are Degraded to Oxaloacetate Chapter Review Key Terms Problems Chapter 19 Oxidative Phosphorylation 19.1 The Mitochondrial Respiratory Chain Electrons Are Funneled to Universal Electron Acceptors Electrons Pass through a Series of Membrane-Bound Carriers Electron Carriers Function in Multienzyme Complexes Mitochondrial Complexes Associate in Respirasomes Other Pathways Donate Electrons to the Respiratory Chain via Ubiquinone The Energy of Electron Transfer Is Efficiently Conserved in a Proton Gradient Reactive Oxygen Species Are Generated during Oxidative Phosphorylation 19.2 ATP Synthesis In the Chemiosmotic Model, Oxidation and Phosphorylation Are Obligately Coupled ATP Synthase Has Two Functional Domains, F[0] and F[1] ATP Is Stabilized Relative to ADP on the Surface of F[1] The Proton Gradient Drives the Release of ATP from the Enzyme Surface Each β Subunit of ATP Synthase Can Assume Three Different Conformations Rotational Catalysis Is Key to the Binding-Change Mechanism for ATP Synthesis Chemiosmotic Coupling Allows Nonintegral Stoichiometries of O[2] Consumption and ATP Synthesis The Proton-Motive Force Energiz