Part I The Molecular Design of Life
SECTION 1 Biochemistry Helps Us to Understand Our World
Chapter 1 Biochemistry and the Unity of Life
1.1 Living Systems Require a Limited Variety of Atoms and Molecules
1.2 There Are Four Major Classes of Biomolecules
Proteins Are Highly Versatile Biomolecules
Nucleic Acids Are the Information Molecules of the Cell
Lipids Are a Storage Form of Fuel and Serve as a Barrier
Carbohydrates Are Fuels and Informational Molecules
1.3 The Central Dogma Describes the Basic Principles of Biological Information Transfer
1.4 Membranes Define the Cell and Carry Out Cellular Functions
Biochemical Functions Are Sequestered in Cellular Compartments
Some Organelles Process and Sort Proteins and Exchange Material with the Environment
Clinical Insight Defects in Organelle Function May Lead to Disease
Chapter 2 Water, Weak Bonds, and the Generation of Order Out of Chaos
2.1 Thermal Motions Power Biological Interactions
2.2 Biochemical Interactions Take Place in an Aqueous Solution
2.3 Weak Interactions Are Important Biochemical Properties
Electrostatic Interactions Are Between Electrical Charges
Hydrogen Bonds Form Between an Electronegative Atom and Hydrogen
van der Waals Interactions Depend on Transient Asymmetry in Electrical Charge
Weak Bonds Permit Repeated Interactions
2.4 Hydrophobic Molecules Cluster Together
Membrane Formation Is Powered by the Hydrophobic Effect
Protein Folding Is Powered by the Hydrophobic Effect
Functional Groups Have Specific Chemical Properties
2.5 pH Is an Important Parameter of Biochemical Systems
Water Ionizes to a Small Extent
An Acid Is a Proton Donor, Whereas a Base Is a Proton Acceptor
Acids Have Differing Tendencies to Ionize
Buffers Resist Changes in pH
Buffers Are Crucial in Biological Systems
Making Buffers Is a Common Laboratory Practice
APPENDIX: Problem-Solving Strategies
SECTION 2 Protein Composition and Structure
Chapter 3 Amino Acids
3.1 Proteins Are Built from a Repertoire of 20 Amino Acids
Most Amino Acids Exist in Two Mirror-Image Forms
All Amino Acids Have at Least Two Charged Groups
3.2 Amino Acids Contain a Wide Array of Functional Groups
Hydrophobic Amino Acids Have Mainly Hydrocarbon Side Chains
Polar Amino Acids Have Side Chains That Contain an Electronegative Atom
Positively Charged Amino Acids Are Hydrophilic
Negatively Charged Amino Acids Have Acidic Side Chains
The Ionizable Side Chains Enhance Reactivity and Bonding
3.3 Essential Amino Acids Must Be Obtained from the Diet
Clinical Insight Pathological Conditions Result If Protein Intake Is Inadequate
APPENDIX: Problem-Solving Strategies
Chapter 4 Protein Three-Dimensional Structure
4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains
Proteins Have Unique Amino Acid Sequences Specified by Genes
Polypeptide Chains Are Flexible Yet Conformationally Restricted
4.2 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures
The Alpha Helix Is a Coiled Structure Stabilized by Intrachain Hydrogen Bonds
Beta Sheets Are Stabilized by Hydrogen Bonding Between Polypeptide Strands
Polypeptide Chains Can Change Direction by Making Reverse Turns and Loops
Fibrous Proteins Provide Structural Support for Cells and Tissues
Clinical Insight Defects in Collagen Structure Result in Pathological Conditions
4.3 Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures
Myoglobin Illustrates the Principles of Tertiary Structure
The Tertiary Structure of Many Proteins Can Be Divided into Structural and Functional Units
4.4 Quaternary Structure: Multiple Polypeptide Chains Can Assemble into a Single Protein
4.5 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure
Proteins Fold by the Progressive Stabilization of Intermediates Rather Than by Random Search
Some Proteins Are Intrinsically Unstructured and Can Exist in Multiple Conformations
Clinical Insight Protein Misfolding and Aggregation Are Associated with Some Neurological Diseases
APPENDIX: Biochemistry in Focus: Surviving desiccation
Chapter 5 Techniques in Protein Biochemistry
5.1 The Proteome Is the Functional Representation of the Genome
5.2 The Purification of a Protein Is the First Step in Understanding Its Function
Proteins Can Be Purified on the Basis of Differences in Their Chemical Properties
Proteins Must Be Removed from the Cell to Be Purified
Proteins Can Be Purified According to Solubility, Size, Charge, and Binding Affinity
Proteins Can Be Separated by Gel Electrophoresis and Displayed
A Purification Scheme Can Be Quantitatively Evaluated
5.3 Immunological Techniques Are Used to Purify and Characterize Proteins
Centrifugation Is a Means of Separating Proteins
Gradient Centrifugation Provides an Assay for the Estradiol–Receptor Complex
Antibodies to Specific Proteins Can Be Generated
Monoclonal Antibodies with Virtually Any Desired Specificity Can Be Readily Prepared
The Estrogen Receptor Can Be Purified by Immunoprecipitation
Proteins Can Be Detected and Quantified with the Use of an Enzyme-Linked Immunosorbent Assay
Western Blotting Permits the Detection of Proteins Separated by Gel Electrophoresis
5.4 Determination of Primary Structure Facilitates an Understanding of Protein Function
Mass Spectrometry Can Be Used to Determine a Protein’s Mass, Identity, and Sequence
Amino Acids Are Sources of Many Kinds of Insight
APPENDIX: Biochemistry in Focus: The development of affinity chromatography
APPENDIX: Problem-Solving Strategies
SECTION 3 Basic Concepts and Kinetics of Enzymes
Chapter 6 Basic Concepts of Enzyme Action
6.1 Enzymes Are Powerful and Highly Specific Catalysts
Proteolytic Enzymes Illustrate the Range of Enzyme Specificity
There Are Six Major Classes of Enzymes
6.2 Many Enzymes Require Cofactors for Activity
6.3 Gibbs Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes
The Free-Energy Change Provides Information About the Spontaneity but Not the Rate of a Reaction
The Standard Free-Energy Change of a Reaction Is Related to the Equilibrium Constant
Enzymes Alter the Reaction Rate but Not the Reaction Equilibrium
6.4 Enzymes Facilitate the Formation of the Transition State
The Formation of an Enzyme–Substrate Complex Is the First Step in Enzymatic Catalysis
The Active Sites of Enzymes Have Some Common Features
The Binding Energy Between Enzyme and Substrate Is Important for Catalysis
Transition-State Analogs Are Potent Inhibitors of Enzymes
APPENDIX: Biochemistry in Focus: Catalytic antibodies demonstrated the importance of selective binding of the transition state to enzymatic activity.
APPENDIX: Problem-Solving Strategies
Chapter 7 Kinetics and Regulation
7.1 Kinetics Is the Study of Reaction Rates
7.2 The Michaelis–Menten Model Describes the Kinetics of Many Enzymes
Clinical Insight Variations in KM Can Have Physiological Consequences
KM and Vmax Values Can Be Determined by Several Means
KM and Vmax Values Are Important Enzyme Characteristics
Kcat/KM Is a Measure of Catalytic Efficiency
Most Biochemical Reactions Include Multiple Substrates
7.3 Allosteric Enzymes Are Catalysts and Information Sensors
Allosteric Enzymes Are Regulated by Products of the Pathways Under Their Control
Allosterically Regulated Enzymes Do Not Conform to Michaelis–Menten Kinetics
Allosteric Enzymes Depend on Alterations in Quaternary Structure
Regulator Molecules Modulate the R<double arrows>T Equilibrium
The Sequential Model Also Can Account for Allosteric Effects
Clinical Insight Loss of Allosteric Control May Result in Pathological Conditions
7.4 Enzymes Can Be Studied One Molecule at a Time
APPENDIX: Derivation of the Michaelis-Menten Equation
APPENDIX: Biochemistry in Focus: There may be multiple causes for a loss of enzyme activity
APPENDIX: Problem-Solving Strategies
Chapter 8 Mechanisms and Inhibitors
8.1 A Few Basic Catalytic Strategies Are Used by Many Enzymes
8.2 Enzyme Activity Can Be Modulated by Temperature, pH, and Inhibitory Molecules
Temperature Enhances the Rate of Enzyme-Catalyzed Reactions
Most Enzymes Have an Optimal pH
Enzymes Can Be Inhibited by Specific Molecules
Reversible Inhibitors Are Kinetically Distinguishable
Irreversible Inhibitors Can Be Used to Map the Active Site
Clinical Insight Penicillin Irreversibly Inactivates a Key Enzyme in Bacterial Cell-Wall Synthesis
8.3 Chymotrypsin Illustrates Basic Principles of Catalysis and Inhibition
Serine 195 Is Required for Chymotrypsin Activity
Chymotrypsin Action Proceeds in Two Steps Linked by a Covalently Bound Intermediate
The Catalytic Role of Histidine 57 Was Demonstrated by Affinity Labeling
Serine Is Part of a Catalytic Triad That Includes Histidine and Aspartic Acid
APPENDIX: Biochemistry in Focus [title to come]
APPENDIX: Problem-Solving Strategies
Chapter 9 Hemoglobin, An Allosteric Protein
9.1 Hemoglobin Displays Cooperative Behavior
9.2 Myoglobin and Hemoglobin Bind Oxygen in Heme Groups
Clinical Insight Functional Magnetic Resonance Imaging Reveals Regions of the Brain Processing Sensory Information
9.3 Hemoglobin Binds Oxygen Cooperatively
9.4 An Allosteric Regulator Determines the Oxygen Affinity of Hemoglobin
Clinical Insight Hemoglobin’s Oxygen Affinity Is Adjusted to Meet Environmental Needs
Biological Insight Hemoglobin Adaptations Allow Oxygen Transport in Extreme Environments
9.5 Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen
9.6 Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease
Clinical Insight Sickle-Cell Anemia Is a Disease Caused by a Mutation in Hemoglobin
Clinical Insight Thalassemia Is Caused by an Imbalanced Production of Hemoglobin Chains
APPENDIX: Biochemistry in Focus: A potential antidote for carbon monoxide poisoning?
APPENDIX: Problem-Solving Strategies
SECTION 4 Carbohydrates and Lipids
Chapter 10 Carbohydrates
10.1 Monosaccharides Are the Simplest Carbohydrates
Many Common Sugars Exist in Cyclic Forms
Pyranose and Furanose Rings Can Assume Different Conformations
Clinical Insight Glucose Is a Reducing Sugar
Monosaccharides Are Joined to Alcohols and Amines Through Glycosidic Bonds
Biological Insight Glucosinolates Protect Plants and Add Flavor to Our Diets
10.2 Monosaccharides Are Linked to Form Complex Carbohydrates
Specific Enzymes Are Responsible for Oligosaccharide Assembly
Sucrose, Lactose, and Maltose Are the Common Disaccharides
Glycogen and Starch Are Storage Forms of Glucose
Cellulose, a Structural Component of Plants, Is Made of Chains of Glucose
Clinical Insight Human Milk Oligosaccharides Protect Newborns from Infection
10.3 Carbohydrates Are Attached to Proteins to Form Glycoproteins
Carbohydrates May Be Linked to Asparagine, Serine, or Threonine Residues of Proteins
Clinical Insight The Hormone Erythropoietin Is a Glycoprotein
Clinical Insight Glycosylation Functions in Nutrient Sensing
Proteoglycans, Composed of Polysaccharides and Protein, Have Important Structural Roles
Clinical Insight Proteoglycans Are Important Components of Cartilage
Clinical Insight Mucins Are Glycoprotein Components of Mucus
Biological Insight Blood Groups Are Based on Protein Glycosylation Patterns
Clinical Insight Lack of Glycosylation Can Result in Pathological Conditions
10.4 Lectins Are Specific Carbohydrate-Binding Proteins
Lectins Promote Interactions Between Cells
Clinical Insight Lectins Facilitate Embryonic Development
Clinical Insight Influenza Virus Binds to Sialic Acid Residues
APPENDIX: Biochemistry in Focus: a-Glucosidase inhibitors can help to maintain blood glucose homeostasis
APPENDIX: Problem-Solving Strategies
Chapter 11 Lipids
11.1 Fatty Acids Are a Main Source of Fuel
Fatty Acids Vary in Chain Length and Degree of Unsaturation
The Degree and Type of Unsaturation Are Important to Health
11.2 Triacylglycerols Are the Storage Form of Fatty Acids
11.3 There Are Three Common Types of Membrane Lipids
Phospholipids Are the Major Class of Membrane Lipids
Membrane Lipids Can Include Carbohydrates
Steroids Are Lipids That Have a Variety of Roles
Biological Insight Membranes of Extremophiles Are Built from Ether Lipids with Branched Chains
Membrane Lipids Contain a Hydrophilic and a Hydrophobic Moiety
Some Proteins Are Modified by the Covalent Attachment of Hydrophobic Groups
Clinical Insight Premature Aging Can Result from the Improper Attachment of a Hydrophobic Group to a Protein
APPENDIX: Biochemistry in Focus: Inappropriate DHA metabolism may result in diabetic retinopathy
APPENDIX: Problem-Solving Strategies
SECTION 5 Cell Membranes, Channels, Pumps, and Receptors
Chapter 12 Membrane Structure and Function
12.1 Phospholipids and Glycolipids Form Bimolecular Sheets
Clinical Insight Lipid Vesicles Can Be Formed from Phospholipids
Lipid Bilayers Are Highly Impermeable to Ions and Most Polar Molecules
12.2 Membrane Fluidity Is Controlled by Fatty Acid Composition and Cholesterol Content
12.3 Proteins Carry Out Most Membrane Processes
Proteins Associate with the Lipid Bilayer in a Variety of Ways
Clinical Insight The Association of Prostaglandin H2 Synthase-l with the Membrane Accounts for the Action of Aspirin
12.4 Lipids and Many Membrane Proteins Diffuse Laterally in the Membrane
12.5 A Major Role of Membrane Proteins Is to Function As Transporters
The Na+–K+ ATPase Is an Important Pump in Many Cells
Clinical Insight Multidrug Resistance Highlights a Family of Membrane Pumps with ATP-Binding Domains
Clinical Insight Harlequin Ichthyosis Is a Dramatic Result of a Mutation in an ABC Transporter Protein
Secondary Transporters Use One Concentration Gradient to Power the Formation of Another
Clinical Insight Digitalis Inhibits the Na+-K+ Pump by Blocking Its Dephosphorylation
Specific Channels Can Rapidly Transport Ions Across Membranes
Biological Insight Venomous Pit Vipers Use Ion Channels to Generate a Thermal Image
The Structure of the Potassium Ion Channel Reveals the Basis of Ion Specificity
The Structure of the Potassium Ion Channel Explains Its Rapid Rate of Transport
APPENDIX: Problem-Solving Strategies
APPENDIX: Biochemistry in Focus: Action potentials are mediated by transient changes in Na+ and K+ permeability
Chapter 13 Signal-Transduction Pathways
13.1 Signal Transduction Depends on Molecular Circuits
13.2 Receptor Proteins Transmit Information into the Cell
Seven-Transmembrane-Helix Receptors Change Conformation in Response to Ligand Binding and Activate G Proteins
Ligand Binding to 7TM Receptors Leads to the Activation of G Proteins
Activated G Proteins Transmit Signals by Binding to Other Proteins
Cyclic AMP Stimulates the Phosphorylation of Many Target Proteins by Activating Protein Kinase A
Clinical Insight Mutations in Protein Kinase A Can Cause Cushing’s Syndrome
G Proteins Spontaneously Reset Themselves Through GTP Hydrolysis
Clinical Insight Cholera and Whooping Cough Are Due to Altered G-Protein Activity
The Hydrolysis of Phosphatidylinositol Bisphosphate by Phospholipase C Generates Two Second Messengers
13.3 Some Receptors Dimerize in Response to Ligand Binding and Recruit Tyrosine Kinases
Receptor Dimerization May Result in Tyrosine Kinase Recruitment
Clinical Insight Some Receptors Contain Tyrosine Kinase Domains Within Their Covalent Structures
Ras Belongs to Another Class of Signaling G Proteins
13.4 Metabolism in Context: Insulin Signaling Regulates Metabolism
The Insulin Receptor Is a Dimer That Closes Around a Bound Insulin Molecule
The Activated Insulin-Receptor Kinase Initiates a Kinase Cascade
Insulin Signaling Is Terminated by the Action of Phosphatases
13.5 Calcium Ion Is a Ubiquitous Cytoplasmic Messenger
13.6 Defects in Signaling Pathways Can Lead to Diseases
Clinical Insight The Conversion of Proto-oncogenes into Oncogenes Disrupts the Regulation of Cell Growth
Clinical Insight Protein Kinase Inhibitors May Be Effective Anticancer Drugs
APPENDIX: Biochemistry in Focus: Olfaction is mediated by an enormous family of seven-transmembrane-helix receptors
APPENDIX: Problem-Solving Strategies
Part II Transducing and Storing Energy
SECTION 6 Basic Concepts and Design of Metabolism
Chapter 14 Digestion: Turning a Meal into Cellular Biochemicals
14.1 Digestion Prepares Large Biomolecules for Use in Metabolism
Most Digestive Enzymes Are Secreted as Inactive Precursors
14.2 Proteases Digest Proteins into Amino Acids and Peptides
Clinical Insight Protein Digestion Begins in the Stomach
Protein Digestion Continues in the Intestine
Clinical Insight Celiac Disease Results from the Inability to Digest Certain Proteins Properly
14.3 Dietary Carbohydrates Are Digested by Alpha-Amylase
14.4 The Digestion of Lipids Is Complicated by Their Hydrophobicity
Biological Insight Snake Venoms Digest from the Inside Out
APPENDIX: Biochemistry in Focus: Enteropeptidase deficiency, although rare, can be life-threatening
APPENDIX: Problem-Solving Strategies
Chapter 15 Metabolism: Basic Concepts and Design
15.1 Energy Is Required to Meet Three Fundamental Needs
15.2 Metabolism Is Composed of Many Interconnecting Reactions
Metabolism Consists of Energy-Yielding Reactions and Energy-Requiring Reactions
A Thermodynamically Unfavorable Reaction Can Be Driven by a Favorable Reaction
15.3 ATP Is the Universal Currency of Free Energy
ATP Hydrolysis Is Exergonic
ATP Hydrolysis Drives Metabolism by Shifting the Equilibrium of Coupled Reactions
The High Phosphoryl-Transfer Potential of ATP Results from Structural Differences Between ATP and Its Hydrolysis Products
Phosphoryl-Transfer Potential Is an Important Form of Cellular Energy Transformation
Clinical Insight Exercise Depends on Various Means of Generating ATP
Phosphates Play a Prominent Role in Biochemical Processes
ATP May Have Roles Other Than in Energy and Signal Transduction
15.4 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
Carbon Oxidation Is Paired with a Reduction
Compounds with High Phosphoryl-Transfer Potential Can Couple Carbon Oxidation to ATP Synthesis
15.5 Metabolic Pathways Contain Many Recurring Motifs
Activated Carriers Exemplify the Modular Design and Economy of Metabolism
Clinical Insight Lack of Activated Pantothenate Results in Neurological Problems
Many Activated Carriers Are Derived from Vitamins
15.6 Metabolic Processes Are Regulated in Three Principal Ways
The Amounts of Enzymes Are Controlled
Catalytic Activity Is Regulated
The Accessibility of Substrates Is Regulated
APPENDIX: Biochemistry in Focus: Loss of NAD compromises muscle function
APPENDIX: Problem-Solving Strategies
SECTION 7 Glycolysis and Gluconeogenesis
Chapter 16 Glycolysis
16.1 Glycolysis Is an Energy-Conversion Pathway
The Enzymes of Glycolysis are Associated With One Another
Glycolysis Can be Divided into Two Parts
Hexokinase Traps Glucose in the Cell and Begins Glycolysis
Fructose 1,6-bisphosphate Is Generated from Glucose 6-Phosphate
Clinical Insight The Six-Carbon Sugar Is Cleaved into Two Three-Carbon Fragments
The Oxidation of an Aldehyde Powers the Formation of a Compound Having High Phosphoryl-Transfer Potential
ATP Is Formed by Phosphoryl Transfer from 1,3-Bisphosphoglycerate
Additional ATP Is Generated with the Formation of Pyruvate
Two ATP Molecules Are Formed in the Conversion of Glucose into Pyruvate
16.2 NAD+ Is Regenerated from the Metabolism of Pyruvate
Fermentations Are a Means of Oxidizing NADH
Biological Insight Fermentations Provide Usable Energy in the Absence of Oxygen
16.3 Fructose and Galactose Are Converted into Glycolytic Intermediates
Fructose Is Converted into Glycolytic Intermediates by Fructokinase
Clinical Insight Excessive Fructose Consumption Can Lead to Pathological Conditions
Galactose Is Converted into Glucose 6-phosphate
Clinical Insight Many Adults Are Intolerant of Milk Because They Are Deficient in Lactase
Clinical Insight Galactose Is Highly Toxic If the Transferase Is Missing
16.4 The Glycolytic Pathway Is Tightly Controlled
Glycolysis in Muscle Is Regulated by Feedback Inhibition to Meet the Need for ATP
The Regulation of Glycolysis in the Liver Corresponds to the Biochemical Versatility of the Liver
A Family of Transporters Enables Glucose to Enter and Leave Animal Cells
Clinical Insight Aerobic Glycolysis Is a Property of Rapidly Growing Cells
Clinical Insight Cancer and Exercise Training Affect Glycolysis in a Similar Fashion
16.5 Metabolism in Context: Glycolysis Helps Pancreatic Beta Cells Sense Glucose
APPENDIX: Biochemistry in Focus: Triose phosphate isomerase deficiency (TPID)
APPENDIX: Problem-Solving Strategies
Chapter 17 Gluconeogenesis
17.1 Glucose Can Be Synthesized from Noncarbohydrate Precursors
Gluconeogenesis Is Not a Complete Reversal of Glycolysis
The Conversion of Pyruvate into Phosphoenolpyruvate Begins with the Formation of Oxaloacetate
Oxaloacetate Is Shuttled into the Cytoplasm and Converted into Phosphoenolpyruvate
The Conversion of Fructose 1,6-bisphosphate into Fructose 6-phosphate and Orthophosphate Is an Irreversible Step
The Generation of Free Glucose Is an Important Control Point
Six High-Transfer-Potential Phosphoryl Groups Are Spent in Synthesizing Glucose from Pyruvate
17.2 Gluconeogenesis and Glycolysis Are Reciprocally Regulated
Energy Charge Determines Whether Glycolysis or Gluconeogenesis Will Be More Active
The Balance Between Glycolysis and Gluconeogenesis in the Liver Is Sensitive to Blood-Glucose Concentration
Clinical Insight Insulin Fails to Inhibit Gluconeogenesis in Type 2 Diabetes
Clinical Insight Substrate Cycles Amplify Metabolic Signals
17.3 Metabolism in Context: Precursors Formed by Muscle Are Used by Other Organs
APPENDIX: Biochemistry in Focus: Pyruvate carboxylase deficiency is a rare but potentially fatal disorder
APPENDIX: Problem-Solving Strategies
SECTION 8 The Citric Acid Cycle
Chapter 18 Preparation for the Cycle
18.1 Pyruvate Dehydrogenase Forms Acetyl Coenzyme A from Pyruvate
The Synthesis of Acetyl Coenzyme A from Pyruvate Requires Three Enzymes and Five Coenzymes
Flexible Linkages Allow Lipoamide to Move Between Different Active Sites
18.2 The Pyruvate Dehydrogenase Complex Is Regulated by Two Mechanisms
Clinical Insight Defective Regulation of Pyruvate Dehydrogenase Results in Lactic Acidosis
Clinical Insight Enhanced Pyruvate Dehydrogenase Kinase Activity Facilitates the Development of Cancer
Clinical Insight The Disruption of Pyruvate Metabolism Is the Cause of Beriberi
APPENDIX: Biochemistry in Focus: Diabetic neuropathy may result from inhibition of the pyruvate dehydrogenase complex
APPENDIX: Problem-Solving Strategies
Chapter 19 Harvesting Electrons from the Cycle
19.1 The Citric Acid Cycle Consists of Two Stages
19.2 Stage One Oxidizes Two Carbon Atoms to Gather Energy-Rich Electrons
Citrate Synthase Forms Citrate from Oxaloacetate and Acetyl Coenzyme A
The Mechanism of Citrate Synthase Prevents Undesirable Reactions
Citrate Is Isomerized into Isocitrate
Isocitrate Is Oxidized and Decarboxylated to Alpha-Ketoglutarate
Succinyl Coenzyme A Is Formed by the Oxidative Decarboxylation of Alpha-Ketoglutarate
19.3 Stage Two Regenerates Oxaloacetate and Harvests Energy-Rich Electrons
A Compound with High Phosphoryl-Transfer Potential Is Generated from Succinyl Coenzyme A
Succinyl Coenzyme A Synthetase Transforms Types of Biochemical Energy
Oxaloacetate Is Regenerated by the Oxidation of Succinate
The Citric Acid Cycle Produces High-Transfer-Potential Electrons, an ATP, and Carbon Dioxide
19.4 The Citric Acid Cycle Is Regulated
The Citric Acid Cycle Is Controlled at Several Points
The Citric Acid Cycle Is a Source of Biosynthetic Precursors
The Citric Acid Cycle Must Be Capable of Being Rapidly Replenished
Clinical Insight Defects in the Citric Acid Cycle Contribute to the Development of Cancer
19.5 The Glyoxylate Cycle Enables Plants and Bacteria to Convert Fats into Carbohydrates
APPENDIX: Biochemistry in Focus: New treatments for tuberculosis may be on the horizon
APPENDIX: Problem-Solving Strategies
SECTION 9 Oxidative Phosphorylation
Chapter 20 The Electron-Transport Chain
20.1 Oxidative Phosphorylation in Eukaryotes Takes Place in Mitochondria
Mitochondria Are Bounded by a Double Membrane
Biological Insight Mitochondria Are the Result of an Endosymbiotic Event
20.2 Oxidative Phosphorylation Depends on Electron Transfer
The Electron-Transfer Potential of an Electron Is Measured as Redox Potential
Electron Flow Through the Electron-Transport Chain Creates a Proton Gradient
The Electron-Transport Chain Is a Series of Coupled Oxidation–Reduction Reactions
Clinical Insight Loss of Iron-Sulfur Cluster Results in Friedreich’s Ataxia
20.3 The Respiratory Chain Consists of Proton Pumps and a Physical Link to the Citric Acid Cycle
The High-Potential Electrons of NADH Enter the Respiratory Chain at NADH-Q Oxidoreductase
Ubiquinol Is the Entry Point for Electrons from FADH2 of Flavoproteins
Electrons Flow from Ubiquinol to Cytochrome c Through Q-Cytochrome c Oxidoreductase
The Q Cycle Funnels Electrons from a Two-Electron Carrier to a One-Electron Carrier and Pumps Protons
Cytochrome c Oxidase Catalyzes the Reduction of Molecular Oxygen to Water
Most of the Electron-Transport Chain Is Organized into a Complex Called the Respirasome
Biological Insight The Dead Zone: Too Much Respiration
Toxic Derivatives of Molecular Oxygen Such As Superoxide Radical Are Scavenged by Protective Enzymes
APPENDIX: Biochemistry in Focus: The conformation of cytochrome c has remained essentially constant for more than a billion years
APPENDIX: Problem-Solving Strategies
Chapter 21 The Proton-Motive Force
21.1 A Proton Gradient Powers the Synthesis of ATP
ATP Synthase Is Composed of a Proton-Conducting Unit and a Catalytic Unit
Proton Flow Through ATP Synthase Leads to the Release of Tightly Bound ATP
Rotational Catalysis Is the World’s Smallest Molecular Motor
Proton Flow Around the c Ring Powers ATP Synthesis
21.2 Shuttles Allow Movement Across Mitochondrial Membranes
Electrons from Cytoplasmic NADH Enter Mitochondria by Shuttles
The Entry of ADP into Mitochondria Is Coupled to the Exit of ATP
Mitochondrial Transporters Allow Metabolite Exchange Between the Cytoplasm and Mitochondria
21.3 Cellular Respiration Is Regulated by the Need for ATP
The Complete Oxidation of Glucose Yields About 30 Molecules of ATP
The Rate of Oxidative Phosphorylation Is Determined by the Need for ATP
Clinical Insight ATP Synthase Can Be Regulated
Biological Insight Regulated Uncoupling Leads to the Generation of Heat
Clinical Insight Oxidative Phosphorylation Can Be Inhibited at Many Stages
Clinical Insight Mitochondrial Diseases Are Being Discovered in Increasing Numbers
Power Transmission by Proton Gradients Is a Central Motif of Bioenergetics
APPENDIX: Biochemistry in Focus: Leber hereditary optic neuropathy can result from defects in Complex I
APPENDIX: Problem-Solving Strategies
SECTION 10 The Light Reactions of Photosynthesis and the Calvin Cycle
Chapter 22 The Light Reactions
22.1 Photosynthesis Takes Place in Chloroplasts
Biological Insight Chloroplasts, Like Mitochondria, Arose from an Endosymbiotic Event
22.2 Photosynthesis Transforms Light Energy into Chemical Energy
Chlorophyll Is the Primary Light Acceptor in Most Photosynthetic Systems
Light-Harvesting Complexes Enhance the Efficiency of Photosynthesis
Biological Insight Chlorophyll in Potatoes Suggests the Presence of a Toxin
22.3 Two Photosystems Generate a Proton Gradient and NADPH
Photosystem I Uses Light Energy to Generate Reduced Ferredoxin, a Powerful Reductant
Photosystem II Transfers Electrons to Photosystem I and Generates a Proton Gradient
Cytochrome b6f ?Links Photosystem II to Photosystem I
The Oxidation of Water Achieves Oxidation–Reduction Balance and Contributes Protons to the Proton Gradient
22.4 A Proton Gradient Drives ATP Synthesis
The ATP Synthase of Chloroplasts Closely Resembles That of Mitochondria
The Activity of Chloroplast ATP Synthase Is Regulated
Cyclic Electron Flow Through Photosystem I Leads to the Production of ATP Instead of NADPH
The Absorption of Eight Photons Yields One O2?, Two NADPH, and Three ATP Molecules
The Components of Photosynthesis Are Highly Organized
Biological Insight Many Herbicides Inhibit the Light Reactions of Photosynthesis
APPENDIX: Biochemistry in Focus: Increasing the efficiency of photosynthesis will increase crop yields
APPENDIX: Problem-Solving Strategies
Chapter 23 The Calvin Cycle
23.1 The Calvin Cycle Synthesizes Hexoses from Carbon Dioxide and Water
Carbon Dioxide Reacts with Ribulose 1,5-bisphosphate to Form Two Molecules of 3-Phosphoglycerate
Hexose Phosphates Are Made from Phosphoglycerate, and Ribulose 1,5-bisphosphate Is Regenerated
Three Molecules of ATP and Two Molecules of NADPH Are Used to Bring Carbon Dioxide to the Level of a Hexose
Biological Insight A Volcanic Eruption Can Affect Photosynthesis Worldwide
Starch and Sucrose Are the Major Carbohydrate Stores in Plants
Biological Insight Why Bread Becomes Stale: The Role of Starch
23.2 The Calvin Cycle Is Regulated by the Environment
Thioredoxin Plays a Key Role in Regulating the Calvin Cycle
Rubisco Also Catalyzes a Wasteful Oxygenase Reaction
The C4 Pathway of Tropical Plants Accelerates Photosynthesis by Concentrating Carbon Dioxide
Crassulacean Acid Metabolism Permits Growth in Arid Ecosystems
APPENDIX: Biochemistry in Focus: A unique property of phosphoenolpyruvate carboxylase makes it useful to evolutionary biologists
APPENDIX: Problem-Solving Strategies
SECTION 11 Glycogen Metabolism and the Pentose Phosphate Pathway
Chapter 24 Glycogen Degradation
24.1 Glycogen Breakdown Requires Several Enzymes
Phosphorylase Cleaves Glycogen to Release Glucose 1-phosphate
A Debranching Enzyme Also Is Needed for the Breakdown of Glycogen
Phosphoglucomutase Converts Glucose 1-phosphate into Glucose 6-phosphate
Liver Contains Glucose 6-phosphatase, a Hydrolytic Enzyme Absent from Muscle
24.2 Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation
Liver Phosphorylase Produces Glucose for Use by Other Tissues
Muscle Phosphorylase Is Regulated by the Intracellular Energy Charge
Biochemical Characteristics of Muscle Fiber Types Differ
Phosphorylation Promotes the Conversion of Phosphorylase b to Phosphorylase a
Phosphorylase Kinase Is Activated by Phosphorylation and Calcium Ions
Clinical Insight Hers Disease Is Due to a Phosphorylase Deficiency
An Isozymic Form of Glycogen Phosphorylase Exists in the Brain
24.3 Epinephrine and Glucagon Signal the Need for Glycogen Breakdown
G Proteins Transmit the Signal for the Initiation of Glycogen Breakdown
Glycogen Breakdown Must Be Rapidly Turned Off When Necessary
Biological Insight Glycogen Depletion Coincides with the Onset of Fatigue
APPENDIX: Biochemistry in Focus: McArdle’s disease results from a lack of skeletal muscle glycogen phosphorylase
APPENDIX: Problem-Solving Strategies
Chapter 25 Glycogen Synthesis
25.1 Glycogen Is Synthesized and Degraded by Different Pathways
UDP-Glucose Is an Activated Form of Glucose
Glycogen Synthase Catalyzes the Transfer of Glucose from UDP-Glucose to a Growing Chain
A Branching Enzyme Forms Alpha-1,6 Linkages
Glycogen Synthase Is the Key Regulatory Enzyme in Glycogen Synthesis
Glycogen Is an Efficient Storage Form of Glucose
25.2 Metabolism in Context: Glycogen Breakdown and Synthesis Are Reciprocally Regulated
Protein Phosphatase 1 Reverses the Regulatory Effects of Kinases on Glycogen Metabolism
Insulin Stimulates Glycogen Synthesis by Inactivating Glycogen Synthase Kinase
Glycogen Metabolism in the Liver Regulates the Blood-Glucose Concentration
Clinical Insight Diabetes Mellitus Results from Insulin Insufficiency and Glucagon Excess
Clinical Insight A Biochemical Understanding of Glycogen-Storage Diseases Is Possible
APPENDIX: Biochemistry in Focus: Ethanol affects glycogen metabolism in the liver
APPENDIX: Problem-Solving Strategies
Chapter 26 The Pentose Phosphate Pathway
26.1 The Pentose Phosphate Pathway Yields NADPH and Five-Carbon Sugars
Two Molecules of NADPH Are Generated in the Conversion of Glucose 6-phosphate into Ribulose 5-phosphate
The Pentose Phosphate Pathway and Glycolysis Are Linked by Transketolase and Transaldolase
26.2 Metabolism in Context: Glycolysis and the Pentose Phosphate Pathway Are Coordinately Controlled
The Rate of the Pentose Phosphate Pathway Is Controlled by the Level of NADP+
The Fate of Glucose 6-phosphate Depends on the Need for NADPH, Ribose 5-phosphate, and ATP
Clinical Insight The Pentose Phosphate Pathway Is Required For Rapid Cell Growth
26.3 Glucose 6-phosphate Dehydrogenase Lessens Oxidative Stress
Clinical Insight Glucose 6-phosphate Dehydrogenase Deficiency Causes a Drug-Induced Hemolytic Anemia
Biological Insight A Deficiency of Glucose 6-phosphate Dehydrogenase Confers an Evolutionary Advantage in Some Circumstances
APPENDIX: Biochemistry in Focus: Hummingbirds and the pentose phosphate pathway
APPENDIX: Problem-Solving Strategies
SECTION 12 Fatty Acid and Lipid Metabolism
Chapter 27 Fatty Acid Degradation
27.1 Fatty Acids Are Processed in Three Stages
Clinical Insight Triacylglycerols Are Hydrolyzed by Hormone-Stimulated Lipases
Free Fatty Acids and Glycerol Are Released into the Blood
Fatty Acids Are Linked to Coenzyme A Before They Are Oxidized
Clinical Insight Pathological Conditions Result if Fatty Acids Cannot Enter the Mitochondria
Acetyl CoA, NADH, and FADH2 Are Generated by Fatty Acid Oxidation
The Complete Oxidation of Palmitate Yields 106 Molecules of ATP
27.2 The Degradation of Unsaturated and Odd-Chain Fatty Acids Requires Additional Steps
An Isomerase and a Reductase Are Required for the Oxidation of Unsaturated Fatty Acids
Odd-Chain Fatty Acids Yield Propionyl CoA in the Final Thiolysis Step
27.3 Ketone Bodies Are Another Fuel Source Derived from Fats
Ketone-Body Synthesis Takes Place in the Liver
Clinical Insight Ketogenic Diets May Have Therapeutic Properties
Animals Cannot Convert Fatty Acids into Glucose
27.4 Metabolism in Context: Fatty Acid Metabolism Is a Source of Insight into Various Physiological States
Clinical Insight Diabetes Can Lead to a Life-Threatening Excess of Ketone-Body Production
Clinical Insight Ketone Bodies Are a Crucial Fuel Source During Starvation
Clinical Insight Some Fatty Acids May Contribute to the Development of Pathological Conditions
APPENDIX: Biochemistry in Focus: Hypoglycin from the ackee fruit inhibits fatty acid oxidation
APPENDIX: Problem-Solving Strategies
Chapter 28 Fatty Acid Synthesis
28.1 Fatty Acid Synthesis Takes Place in Three Stages
Citrate Carries Acetyl Groups from Mitochondria to the Cytoplasm
Several Sources Supply NADPH for Fatty Acid Synthesis
The Formation of Malonyl CoA Is the Committed Step in Fatty Acid Synthesis
Fatty Acid Synthesis Consists of a Series of Condensation, Reduction, Dehydration, and Reduction Reactions
The Synthesis of Palmitate Requires 8 Molecules of Acetyl CoA, 14 Molecules of NADPH, and 7 Molecules of ATP
Fatty Acids Are Synthesized by a Multifunctional Enzyme Complex in Animals
Clinical Insight Fatty Acid Metabolism Is Altered in Tumor Cells
Clinical Insight A Small Fatty Acid That Causes Big Problems
28.2 Additional Enzymes Elongate and Desaturate Fatty Acids
Membrane-Bound Enzymes Generate Unsaturated Fatty Acids
Eicosanoid Hormones Are Derived from Polyunsaturated Fatty Acids
Clinical Insight Aspirin Exerts Its Effects by Covalently Modifying a Key Enzyme
28.3 Acetyl CoA Carboxylase Is a Key Regulator of Fatty Acid Metabolism
Acetyl CoA Carboxylase Is Regulated by Conditions in the Cell
Acetyl CoA Carboxylase Is Regulated by a Variety of Hormones
AMP-Activated Protein Kinase Is a Key Regulator of Metabolism
28.4 Metabolism in Context: Ethanol Alters Energy Metabolism in the Liver
APPENDIX: Biochemistry in Focus: Inhibitors of acetyl CoA carboxylases may be used to treat metabolic disorders
APPENDIX: Problem-Solving Strategies
Chapter 29 Lipid Synthesis: Storage Lipids, Phospholipids, and Cholesterol
29.1 Phosphatidate Is a Precursor of Storage Lipids and Many Membrane Lipids
Triacylglycerol Is Synthesized from Phosphatidate in Two Steps
Phospholipid Synthesis Requires Activated Precursors
Clinical Insight Phosphatidylcholine Is an Abundant Phospholipid
Sphingolipids Are Synthesized from Ceramide
Clinical Insight Gangliosides Serve as Binding Sites for Pathogens
Clinical Insight Disrupted Lipid Metabolism Results in Respiratory Distress Syndrome and Tay–Sachs Disease
Phosphatidic Acid Phosphatase Is a Key Regulatory Enzyme in Lipid Metabolism
29.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages
The Synthesis of Mevalonate Initiates the Synthesis of Cholesterol
Squalene (C30) Is Synthesized from Six Molecules of Isopentenyl Pyrophosphate (C5)
Squalene Cyclizes to Form Cholesterol
29.3 The Regulation of Cholesterol Synthesis Takes Place at Several Levels
29.4 Lipoproteins Transport Cholesterol and Triacylglycerols Throughout the Organism
Low-Density Lipoproteins Play a Central Role in Cholesterol Metabolism
Clinical Insight Inability to Transport Cholesterol from the Lysosome Causes Niemann- Pick Disease
Clinical Insight The Absence of the LDL Receptor Leads to Familial Hypercholesterolemia and Atherosclerosis
Clinical Insight Cycling of the LDL Receptor Is Regulated
Clinical Insight HDL Seems to Protect Against Atherosclerosis
Clinical Insight The Clinical Management of Cholesterol Levels Can Be Understood at a Biochemical Level
29.5 Important Biochemicals Are Synthesized from Cholesterol and Isoprene
Clinical Insight Bile Salts Facilitate Lipid Absorption
Steroid Hormones Are Crucial Signal Molecules
Vitamin D Is Derived from Cholesterol by the Energy of Sunlight
Clinical Insight Vitamin D Is Necessary for Bone Development
Clinical Insight Androgens Can Be Used to Artificially Enhance Athletic Performance
Oxygen Atoms Are Added to Steroids by Cytochrome P450 Monooxygenases
Metabolism in Context: Ethanol Also Is Processed by the Cytochrome P450 System
Five-Carbon Units Are Joined to form a Wide Variety of Biomolecules
APPENDIX: Biochemistry in Focus: Excess ceramides may cause insulin insensitivity
APPENDIX: Problem-Solving Strategies
SECTION 13 The Metabolism of Nitrogen-Containing Molecules
Chapter 30 Amino Acid Degradation and the Urea Cycle
30.1 Nitrogen Removal Is the First Step in the Degradation of Amino Acids
Alpha-Amino Groups Are Converted into Ammonium Ions by the Oxidative Deamination of Glutamate
Clinical Insight Blood Levels of Amonitransferases Serve a Diagnostic Function
Serine and Threonine Can Be Directly Deaminated
Peripheral Tissues Transport Nitrogen to the Liver
30.2 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates
Carbamoyl Phosphate Synthetase Is the Key Regulatory Enzyme for Urea Synthesis
Carbamoyl Phosphate Reacts with Ornithine to Begin the Urea Cycle
The Urea Cycle Is Linked to Gluconeogenesis
Clinical Insight Metabolism in Context: Inherited Defects of the Urea Cycle Cause Hyperammonemia
Biological Insight Hibernation Presents Nitrogen Disposal Problems
Biological Insight Urea Is Not the Only Means of Disposing of Excess Nitrogen
30.3 Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates
Pyruvate Is a Point of Entry into Metabolism
Oxaloacetate Is Another Point of Entry into Metabolism
Alpha-Ketoglutarate Is Yet Another Point of Entry into Metabolism
Succinyl Coenzyme A Is a Point of Entry for Several Amino Acids
Threonine Deaminase Initiates the Degradation of Threonine
Methionine Is Degraded into Succinyl Coenzyme A
The Branched-Chain Amino Acids Yield Acetyl Coenzyme A, Acetoacetate, or Succinyl Coenzyme A
Oxygenases Are Required for the Degradation of Aromatic Amino Acids
Protein Metabolism Helps to Power the Flight of Migratory Birds
Clinical Insight Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation
Clinical Insight Determining the Basis of the Neurological Symptoms of Phenylketonuria Is an Active Area of Research
APPENDIX: Biochemistry in Focus: Methylmalonic acidemia results from an inborn error of metabolism
APPENDIX: Problem-Solving Strategies
Chapter 31 Amino Acid Synthesis
31.1 The Nitrogenase Complex Fixes Nitrogen
The Molybdenum–Iron Cofactor of Nitrogenase Binds and Reduces Atmospheric Nitrogen
Ammonium Ion Is Incorporated into an Amino Acid Through Glutamate and Glutamine
31.2 Amino Acids Are Made from Intermediates of Major Pathways
Human Beings Can Synthesize Some Amino Acids but Must Obtain Others from the Diet
Some Amino Acids Can Be Made by Simple Transamination Reactions
Serine, Cysteine, and Glycine Are Formed from 3-Phosphoglycerate
Clinical Insight Tetrahydrofolate Carries Activated One-Carbon Units
S-Adenosylmethionine Is the Major Donor of Methyl Groups
Clinical Insight High Homocysteine Levels Correlate with Vascular Disease
31.3 Feedback Inhibition Regulates Amino Acid Biosynthesis
The Committed Step Is the Common Site of Regulation
Branched Pathways Require Sophisticated Regulation
31.4 Amino Acids Are Precursors of Many Biomolecules
APPENDIX: Biochemistry in Focus: Tyrosine is a precursor for human pigments
APPENDIX: Problem-Solving Strategies
Chapter 32 Nucleotide Metabolism
32.1 An Overview of Nucleotide Biosynthesis and Nomenclature
32.2 The Pyrimidine Ring Is Assembled and Then Attached to a Ribose Sugar
CTP Is Formed by the Amination of UTP
Kinases Convert Nucleoside Monophosphates into Nucleoside Triphosphates
Clinical Insight Salvage Pathways Recycle Pyrimidine Bases
32.3 The Purine Ring Is Assembled on Ribose Phosphate
AMP and GMP Are Formed from IMP
Biological Insight Enzymes of the Purine-Synthesis Pathway Are Associated with One Another in Vivo
Bases Can Be Recycled by Salvage Pathways
32.4 Ribonucleotides Are Reduced to Deoxyribonucleotides
Thymidylate Is Formed by the Methylation of Deoxyuridylate
Clinical Insight Several Valuable Anticancer Drugs Block the Synthesis of Thymidylate
32.5 Nucleotide Biosynthesis Is Regulated by Feedback Inhibition
Pyrimidine Biosynthesis Is Regulated by Aspartate Transcarbamoylase
The Synthesis of Purine Nucleotides Is Controlled by Feedback Inhibition at Several Sites
Clinical Insight The Synthesis of Deoxyribonucleotides Is Controlled by the Regulation of Ribonucleotide Reductase
32.6 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions
Clinical Insight The Loss of Adenosine Deaminase Activity Results in Severe Combined Immunodeficiency
Clinical Insight Gout Is Induced by High Serum Levels of Urate
Clinical Insight Lesch–Nyhan Syndrome Is a Dramatic Consequence of Mutations in a Salvage-Pathway Enzyme
Clinical Insight Folic Acid Deficiency Promotes Birth Defects Such As Spina Bifida
APPENDIX: Biochemistry in Focus: Uridine Plays a Role in Caloric Homeostasis
APPENDIX: Problem-Solving Strategies
Part III Synthesizing the Molecules of Life
Section 14 Nucleic Acid Structure and DNA Replication
Chapter 33 The Structure of Informational Macromolecules: DNA and RNA
33.1 A Nucleic Acid Consists of Bases Linked to a Sugar–Phosphate Backbone
DNA and RNA Differ in the Sugar Component and One of the Bases
Nucleotides Are the Monomeric Units of Nucleic Acids
DNA Molecules Are Very Long and Have Directionality
33.2 Nucleic Acid Strands Can Form a Double-Helical Structure
The Double Helix Is Stabilized by Hydrogen Bonds and the Hydrophobic Effect
The Double Helix Facilitates the Accurate Transmission of Hereditary Information
Meselson and Stahl Demonstrated That Replication Is Semiconservative
The Strands of the Double Helix Can Be Reversibly Separated
33.3 DNA Double Helices Can Adopt Multiple Forms
Z-DNA Is a Left-Handed Double Helix in Which Backbone Phosphoryl Groups Zigzag
The Major and Minor Grooves Are Lined by Sequence-Specific Hydrogen-Bonding Groups
Double-Stranded DNA Can Wrap Around Itself to Form Supercoiled Structures
Clinical Insight Unusual Circular DNA Exists in the Eukaryotic Nucleus
33.4 Eukaryotic DNA Is Associated with Specific Proteins
Nucleosomes Are Complexes of DNA and Histones
Eukaryotic DNA Is Wrapped Around Histones to Form Nucleosomes
Clinical Insight Damaging DNA Can Inhibit Cancer-Cell Growth
33.5 RNA Can Adopt Elaborate Structures
APPENDIX: Biochemistry in Focus: Protecting against sunburn may result in the death of coral reefs
APPENDIX: Problem-Solving Strategies
Chapter 34 DNA Replication
34.1 DNA Is Replicated by Polymerases
DNA Polymerase Catalyzes Phosphodiester-Linkage Formation
The Specificity of Replication Is Dictated by the Complementarity of Bases
Clinical Insight The Separation of DNA Strands Requires Specific Helicases and ATP Hydrolysis
Topoisomerases Prepare the Double Helix for Unwinding
Clinical Insight Bacterial Topoisomerase Is a Therapeutic Target
Many Polymerases Proofread the Newly Added Bases and Excise Errors
34.2 DNA Replication Is Highly Coordinated
DNA Replication in E. coli Begins at a Unique Site
An RNA Primer Synthesized by Primase Enables DNA Synthesis to Begin
One Strand of DNA Is Made Continuously and the Other Strand Is Synthesized in Fragments
DNA Replication Requires Highly Processive Polymerases
The Leading and Lagging Strands Are Synthesized in a Coordinated Fashion
DNA Replication Is Terminated atDistinct Sites in E. coli
DNA Synthesis Is More Complex in Eukaryotes Than in Bacteria
Telomeres Are Unique Structures at the Ends of Linear Chromosomes
Clinical Insight Telomeres Are Replicated by Telomerase, a Specialized Polymerase That Carries Its Own RNA Template
APPENDIX: Biochemistry in Focus: [title to come]
APPENDIX: Problem-Solving Strategies
Chapter 35 DNA Repair and Recombination
35.1 Errors Can Arise in DNA Replication
Clinical Insight Some Genetic Diseases Are Caused by the Expansion of Repeats of Three Nucleotides
Bases Can Be Damaged by Oxidizing Agents, Alkylating Agents, and Light
35.2 DNA Damage Can Be Detected and Repaired
The Presence of Thymine Instead of Uracil in DNA Permits the Repair of Deaminated Cytosine
Clinical Insight Many Cancers Are Caused by the Defective Repair of DNA
Clinical Insight Many Potential Carcinogens Can Be Detected by Their Mutagenic Action on Bacteria
35.3 DNA Recombination Plays Important Roles in Replication and Repair
Double Strand Breaks Can Be Repaired by Recombination
DNA Recombination Is Important in a Variety of Biological Processes
APPENDIX: Biochemistry in Focus: Drugs can target DNA repair in cancer cells
APPENDIX: Problem-Solving Strategies
SECTION 15 RNA Synthesis, Processing, and Regulation
Chapter 36 RNA Synthesis and Regulation in Bacteria
36.1 Cellular RNA Is Synthesized by RNA Polymerases
Genes Are the Transcriptional Units
RNA Polymerase Is Composed of Multiple Subunits
36.2 RNA Synthesis Comprises Three Stages
Transcription Is Initiated at Promoter Sites on the DNA Template
Sigma Subunits of RNA Polymerase Recognize Promoter Sites
RNA Strands Grow in the 5’-to-3’ Direction
Elongation Takes Place at Transcription Bubbles That Move Along the DNA Template
An RNA Hairpin Followed by Several Uracil Residues Terminates the Transcription of Some Genes
The Rho Protein Helps Terminate the Transcription of Some Genes
Precursors of Transfer and Ribosomal RNA Are Cleaved and Chemically Modified After Transcription
Clinical Insight Some Antibiotics Inhibit Transcription
36.3 The lac Operon Illustrates the Control of Bacterial Gene Expression
An Operon Consists of Regulatory Elements and Protein-Encoding Genes
Ligand Binding Can Induce Structural Changes in Regulatory Proteins
Transcription Can Be Stimulated by Proteins That Contact RNA Polymerase
Clinical and Biological Insight Many Bacterial Cells Release Chemical Signals That Regulate Gene Expression in Other Cells
Some Messenger RNAs Directly Sense Metabolite Concentrations
APPENDIX: Biochemistry in Focus: Attenuation is a prokaryotic mechanism for regulating transcription through the modulation of nascent RNA secondary structure
APPENDIX: Problem-Solving Strategies
Chapter 37 Gene Expression in Eukaryotes
37.1 Eukaryotic Cells Have Three Types of RNA Polymerases
37.2 RNA Polymerase II Requires Complex Regulation
The Transcription Factor IID Protein Complex Initiates the Assembly of the Active Transcription Complex
Enhancer Sequences Can Stimulate Transcription at Start Sites Thousands of Bases Away
Clinical Insight Inappropriate Enhancer Use May Cause Cancer
Multiple Transcription Factors Interact with Eukaryotic Promoters and Enhancers
Clinical Insight Induced Pluripotent Stem Cells Can Be Generated by Introducing Four Transcription Factors into Differentiated Cells
37.3 Gene Expression Is Regulated by Hormones
Nuclear Hormone Receptors Have Similar Domain Structures
Nuclear Hormone Receptors Recruit Coactivators and Corepressors
Clinical Insight Steroid-Hormone Receptors Are Targets for Drugs
37.4 The Control of Gene Expression Can Require Chromatin Remodeling
Metabolism in Context: Acetyl CoA Plays a Key Role in the Regulation of Transcription
Histone Deacetylases Contribute to Transcriptional Repression
The Methylation of DNA Can Alter Patterns of Gene Expression
APPENDIX: Biochemistry in Focus: Mutations in a transcription factor cause extreme skin fragility
APPENDIX: Problem-Solving Strategies
Chapter 38 RNA Processing in Eukaryotes
38.1 Mature Ribosomal RNA Is Generated by the Cleavage of a Precursor Molecule
38.2 Transfer RNA Is Extensively Processed
38.3 Messenger RNA Is Modified and Spliced
Sequences at the Ends of Introns Specify Splice Sites in mRNA Precursors
Small Nuclear RNAs in Spliceosomes Catalyze the Splicing of mRNA Precursors
Clinical Insight Mutations That Affect Pre-mRNA Splicing Cause Disease
Clinical Insight Most Human Pre-mRNAs Can Be Spliced in Alternative Ways to Yield Different Proteins
The Transcription and Processing of mRNA Are Coupled
Biological Insight RNA Editing Changes the Proteins Encoded by mRNA
38.4 RNA Can Function as a Catalyst
APPENDIX: Biochemistry in Focus: [title to come]
APPENDIX: Problem-Solving Strategies
SECTION 16 Protein Synthesis and Recombinant DNA Techniques
Chapter 39 The Genetic Code
39.1 The Genetic Code Links Nucleic Acid and Protein Information
The Genetic Code Is Nearly Universal
Transfer RNA Molecules Have a Common Design
Some Transfer RNA Molecules Recognize More Than One Codon Because of Wobble in Base-Pairing
The Synthesis of Long Proteins Requires a Low Error Frequency
39.2 Amino Acids Are Activated by Attachment to Transfer RNA
Amino Acids Are First Activated by Adenylation
Aminoacyl-tRNA Synthetases Have Highly Discriminating Amino Acid Activation Sites
Proofreading by Aminoacyl-tRNA Synthetases Increases the Fidelity of Protein Synthesis
Synthetases Recognize the Anticodon Loops and Acceptor Stems of Transfer RNA Molecules
39.3 A Ribosome Is a Ribonucleoprotein Particle Made of Two Subunits
Ribosomal RNAs Play a Central Role in Protein Synthesis
Messenger RNA Is Translated in the 5’-to-3’ Direction
APPENDIX: Biochemistry in Focus: Some amino-acyl tRNA synthetases have multiple roles
APPENDIX: Problem-Solving Strategies
Chapter 40 The Mechanism of Protein Synthesis
40.1 Protein Synthesis Decodes the Information in Messenger RNA
Ribosomes Have Three tRNA-Binding Sites That Bridge the 30S and 50S Subunits
The Start Signal Is AUG Preceded by Several Bases That Pair with 16S Ribosomal RNA
Bacterial Protein Synthesis Is Initiated by Formylmethionyl Transfer RNA
Formylmethionyl-tRNAf Is Placed in the P Site of the Ribosome in the Formation of the 70S Initiation Complex
Elongation Factors Deliver Aminoacyl-tRNA to the Ribosome
40.2 Peptidyl Transferase Catalyzes Peptide-Bond Synthesis
The Formation of a Peptide Bond Is Followed by the GTP-Driven Translocation of tRNAs and mRNA
Protein Synthesis Is Terminated by Release Factors That Read Stop Codons
40.3 Bacteria and Eukaryotes Differ in the Initiation of Protein Synthesis
Clinical Insight Mutations in Initiation Factor 2 Cause a Curious Pathological Condition
40.4 A Variety of Biomolecules Can Inhibit Protein Synthesis
Clinical Insight Some Antibiotics Inhibit Protein Synthesis
Clinical Insight Diphtheria Toxin Blocks Protein Synthesis in Eukaryotes by Inhibiting Translocation
Clinical Insight Ricin Fatally Modifies 28S Ribosomal RNA
40.5 Ribosomes Bound to the Endoplasmic Reticulum Manufacture Secretory and Membrane Proteins
Protein Synthesis Begins on Ribosomes That Are Free in the Cytoplasm
Signal Sequences Mark Proteins for Translocation Across the Endoplasmic Reticulum Membrane
40.6 Protein Synthesis Is Regulated by a Number of Mechanisms
Messenger RNA Use Is Subject to Regulation
The Stability of Messenger RNA Also Can Be Regulated
Small RNAs Can Regulate mRNA Stability and Use
Chapter 41 Recombinant DNA Techniques
41.1 Nucleic Acids Can Be Synthesized from Protein-Sequence Data
Protein Sequence Is a Guide to Nucleic Acid Information
DNA Probes Can Be Synthesized by Automated Methods
41.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology
Restriction Enzymes Split DNA into Specific Fragments
Restriction Fragments Can Be Separated by Gel Electrophoresis and Visualized
Restriction Enzymes and DNA Ligase Are Key Tools for Forming Recombinant DNA Molecules
41.3 Eukaryotic Genes Can Be Manipulated with Considerable Precision
Complementary DNA Prepared from mRNA Can Be Expressed in Host Cells
Estrogen-Receptor cDNA Can Be Identified by Screening a cDNA Library
Complementary DNA Libraries Can Be Screened for Synthesized Protein
Specific Genes Can Be Cloned from Digests of Genomic DNA
DNA Can Be Sequenced by the Controlled Termination of Replication
Clinical and Biological Insight Next-Generation Sequencing Methods Enable the Rapid Determination of a Complete Genome Sequence
Selected DNA Sequences Can Be Greatly Amplified by the Polymerase Chain Reaction
Clinical and Biological Insight PCR Is a Powerful Technique in Medical Diagnostics, Forensics, and Studies of Molecular Evolution
Gene-Expression Levels Can Be Comprehensively Examined
Appendices
Glossary
Answers to Problems
Index
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