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 Oxygen Diffusion

There Are Three Distinct Domains of Life

Escherichia coli Is the Most-Studied Prokaryotic Cell

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

Box 1-1 Molecular Weight，Molecular Mass，and Their Correct Units

Three-Dimensional Structure Is Described by Configuration and Conformation

Box 1-2 Louis Pasteur and Optical Activity：In Vino，Veritas

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

The Flow of Electrons Provides Energy for Organisms

Creating and Maintaining Order Requires Work and Energy

Energy Coupling Links Reactions in Biology

Box 1-3 Entropy：The Advantages of Being Disorganized

Keq 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 for Its Replication and Repair with Near-Perfect Fidetyty

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

Chemical Evolution Can Be Simulated in the Laboratory

RNA or Related Precursors May Have Been the First Genes and Catalysts

Biological Evolution Began More Than Three and a Half Biliion Years Ago

The First Cell Was Probably a Chemoheterotroph

Eukaryotic Cells Evolved from Prokaryotes in Several Stages

Molecular Anatomy Reveals Evolutionary Relationships

Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes

Genomic Comparisons Will Have Increasing Importance in Human Biology and Medicine

Ⅰ STRUCTURE AND CATALYSIS

2 Water

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

Entropy Increases as Crystalline Substances Dissolve

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

Solutes Affect the Colligative Properties of Aqueous Solutions

Box 2-1 Touch Response in Plants：An Osmotic Event

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 OH-Concentrations

Box 2-2 The Ion Product of Water：Two Illustrative Problems

Weak Acids and Bases Have Characteristic Dissociation Constants

Titration Curves Reveal the pKa of Weak Acids

2.3 Buffering against pH Changes in Biological Systems

Buffers Are Mixtures of Weak Acids and Their Conjugate Bases

A Simple Expression Relates pH，pKa，and Buffer Concentration

Weak Acids or Bases Buffer Cells and Tissues against pH Changes

Box 2-3 Solving Problems Using the Henderson-Hasselbalch Equation

Box 2-4 Blood，Lungs，and Buffer：The Bicarbonate Buffer System

2.4 Water as a Reactant

2.5 The Fitness of the Aqueous Environment for Living Organisms

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

Box 3-1 Absorption of Light by Molecules：The Lambert-BeerLaw

Amino Acids Have Characteristic Titration Curves

Titration Curves Predict the Electric Charge of AminoAcids

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

Polypeptides Have Characteristic Amino Acid Compositions

Some Proteins Contain Chemical Groups Other Than Amino Acids

There Are Several Levels of Protein Structure

3.3 Working with Proteins

Proteins Can Be Separated and Purified

Proteins Can Be Separated and Characterized by Electrophoresis

Unseparated Proteins Can Be Quantified

3.4 The Covalent Structure of Proteins

The Function of a Protein Depends on Its Amino Acid Sequence

The Amino Acid Sequences of Millions of Proteins Have Been Determined

Short Polypeptides Are Sequenced Using Automated Procedures

Large Proteins Must Be Sequenced in Smaller Segments

Amino Acid Sequences Can Also Be Deduced by Other Methods

Box 3-2 Investigating Proteins with Mass Spectrometry

Small Peptides and Proteins Can Be Chemically Synthesized

Amino Acid Sequences Provide Important Biochemical Information

3.5 Protein Sequences and Evolution

Protein Sequences Can Elucidate the History of Life on Earth

4 The Three-Dimensional Structure of Proteins

4.1 Overview of Protein Structure

A Protein’s Conformation Is Stabilized Largely by Weak Interactions

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 α Helix Stability

Box 4-1 Knowing the Right Hand from the Left

The β Conformation Organizes Polypeptide Chains into Sheets

β Turns Are Common in Proteins

Common Secondary Structures Have Characteristic Bond Angles and Amino Acid Content

4.3 Protein Tertiary and Quaternary Structures

Fibrous Proteins Are Adapted for a Structural Function

Box 4-2 Permanent Waving Is Biochemical Engineering

Structural Diversity Reflects Functional Diversity in Globular Proteins

Box 4-3 Why Sailors，Explorers，and College Students Should Eat Their Fresh Fruits and Vegetables

Myoglobin Provided Early Clues about the Complexity of Globular Protein Structure

Globular Proteins Have a Variety of Tertiary Structures

Box 4-4 Methods for Determining the Three-Dimensional Structure of a Protein

Analysis of Many Globular Proteins Reveals Common Structural Patterns

Protein Motifs Are the Basis for Protein Structural Classification

Protein Quaternary Structures Range from Simple Dimers to Large Complexes

There Are Limits to the Size of Proteins

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

Box 4-5 Death by Misfolding：The Prion Diseases

Some Proteins Undergo Assisted Folding

5 Protein Function

5.1 Reversible Binding of a Protein to a Ligand：Oxygen-Binding Proteins

Oxygen Can Be Bound to a Heme Prosthetic Group

Myoglobin Has a Single Binding Site for Oxygen

Protein-Ligand Interactions Can Be Described Quantitatively

Protein Structure Affects How Ligands Bind

Oxygen Is Transported in Blood by Hemoglobin

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

Box 5-1 Carbon Monoxide：A Stealthy Killer

Hemoglobin Also Transports H＋ and CO2

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 Features a Specialized Array of Cells and Proteins

Self Is Distinguished from Nonself by the Display of Peptides on Cell Surfaces

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

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

Weak Interactions between Enzyme and Substrate Are Optimized in the Transition State

Binding Energy Contributes to Reaction Specificity and Catalysis

Specific Catalytic Groups 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 Quantitatively

Kinetic Parameters Are Used to Compare Enzyme Activities

Box 6-1 Transformations of the Michaelis-Menten Equation：The Double Reciprocal Plot

Many Enzymes Catalyze Reactions with Two or More Substrates

Pre-Steady State Kinetics Can Provide Evidence for Specific Reaction Steps

Enzymes Are Subject to Reversible or Irreversible Inhibition

Box 6-2 Kinetic Tests for Determining Inhibition Mechanisms

Enzyme Activity Depends on pH

6.4 Examples of Enzymatic Reactions

The Chymotrypsin Mechanism Involves Acylation and Deacylation of a Ser Residue

Hexokinase Undergoes Induced Fit on Substrate Binding

The Enolase Reaction Mechanism Requires Metal Ions

Box 6-3 Evidence for Enzyme-Transition State Complementarity

Lysozyme Uses Two Successive Nucleophilic Displacement Reactions

6.5 Regulatory Enzymes

Allosteric Enzymes Undergo Conformational Changes in Response to Modulator Binding

In Many Pathways a Regulated Step Is Catalyzed by an Allosteric Enzyme

The Kinetic Properties of Allosteric Enzymes Diverge from Michaelis-Menten Behavior

Some Regulatory Enzymes Undergo Reversible Covalent Modification

Phosphoryl Groups Affect the Structure and Catalytic Activity of Proteins

Multiple Phosphorylations Allow Exquisite Regulatory Control

Some Enzymes and Other Proteins Are Regulated by Proteolytic Cleavage of an Enzyme Precursor

Some Regulatory Enzymes Use Several Regulatory Mechanisms

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

Monosaccharides Are Reducing Agents

Disaccharides Contain a Glycosidic Bond

7.2 Polysaccharides

Some Homopolysaccharides Are Stored Forms of Fuel

Some Homopolysaccharides Serve Structural Roles

Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding

Bacterial and Algal Cell Walls Contain Structural Heteropolysaccharides

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

Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes

Lectin-Carbohydrate Interactions Are Very Strong and Highly Specific

7.5 Working with Carbohydrates

8 Nucleotides and Nucleic Acids

8.1 Some Basics

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 Stores Genetic Information

DNA Molecules Have Distinctive Base Compositions

DNA Is a Double Helix

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

Nucleic Acids from Different Species Can Form Hybrids

Nucleotides and Nucleic Acids Undergo Nonenzymatic Transformations

Some Bases of DNA Are Methylated

The Sequences of Long DNA Strands Can Be Determined

The Chemical Synthesis of DNA Has Been Automated

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

9 DNA-Based Information Technologies

9.1 DNA Cloning：The Basics

Restriction Endonucleases and DNA Ligase Yield Recombinant DNA

Cloning Vectors Allow Amplification of Inserted DNA Segments

Specific DNA Sequences Are Detectable by Hybridization

Expression of Cloned Genes Produces Large Quantities of Protein

Alterations in Cloned Genes Produce Modified Proteins

9.2 From Genes to Genomes

DNA Libraries Provide Specialized Catalogs of Genetic Information

The Polymerase Chain Reaction Amplifies Specific DNA Sequences

Genome Sequences Provide the Ultimate Genetic Libraries

Box 9-1 A Potent Weapon in Forensic Medicine

9.3 From Genomes to Proteomes

Sequence or Structural Relationships Provide Information on Protein Function

Cellular Expression Patterns Can Reveal the Cellular Function of a Gene

Detection of Protein-Protein Interactions Helps to Define Cellular and Molecular Function

9.4 Genome Alterations and New Products of Biotechnology

A Bacterial Plant Parasite Aids Cloning in Plants

Manipulation of Animal Cell Genomes Provides Information on Chromosome Structure and Gene Expression

New Technologies Promise to Expedite the Discovery of New Pharmaceuticals

Box 9-2 The Human Genome and Human Gene Therapy

Recombinant DNA Technology Yields New Products and Challenges

10 Lipids

10.1 Storage Lipids

Fatty Acids Are Hydrocarbon Derivatives

Triacylglycerols Are Fatty Acid Esters of Glycerol

Triacylglycerols Provide Stored Energy and Insulation

Many Foods Contain Triacylglycerols

Box 10-1 Sperm Whales：Fatheads of the Deep

Waxes Serve as Energy Stores and Water Repellents

10.2 Structural Lipids in Membranes

Glycerophospholipids Are Derivatives of Phosphatidic Acid

Some Phospholipids Have Ether-Linked Fatty Acids

Chloroplasts Contain Galactolipids and Sulfolipids

Archaebacteria Contain Unique Membrane Lipids

Sphingolipids Are Derivatives of Sphingosine

Sphingolipids at Cell Surfaces Are Sites of Biological Recognition

Phospholipids and Sphingoli pids Are Degraded in Lysosomes

Sterols Have Four Fused Carbon Rings

Box 10-2 Inherited Human Diseases Resulting from Abnormal Accumulations of Membrane Lipids

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

Plants Use Phosphatidylinositols，Steroids，and Eicosanoidlike Compounds in Signaling

Vitamins A and D Are Hormone Precursors

Vitamins E and K and the Lipid Quinones Are Oxidation-Reduction Cofactors

Dolichols Activate Sugar Precursor for Biosynthesis

10.4 Working with Lipids

Lipid Extraction Requires Organic Solvents

Adsorption Chromatography Separates Lipids of Different Polarity

Gas-Liquid Chromatography Resolves Mixtures of Volatile Lipid Derivatives

Specific Hydrolysis Aids in Determination of Lipid Structure

Mass Spectrometry Reveals Complete Lipid Structure

11 Biological Membranes and Transport

11.1 The Composition and Architecture of Membranes

Each Type of Membrane Has Characteristic Lipids and Proteins

All Biological Membranes Share Some Fundamental Properties

A Lipid Bilayer Is the Basic Structural Element of Membranes

Peripheral Membrane Proteins Are Easily Solubilized

Many Membrane Proteins Span the Lipid Bilayer

Integral Proteins Are Held in the Membrane by Hydrophobic Interactions with Lipids

The Topology of an Integral Membrane Protein Can Be Predicted from Its Sequence

Covalently Attached Lipids Anchor 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

Box 11-1 Atomic Force Microscopy to Visualize Membrane Proteins

Sphingolipids and Cholesterol Cluster Together in Membrane Rafts

Caveolins Define a Special Class of Membrane Rafts

Certain Integral Proteins Mediate Cell-Cell Interactions and Adhesion

Membrane Fusion Is Central to Many Biological Processes

11.3 Solute Transport across Membranes

Passive Transport Is Facilitated by Membrane Proteins

Transporters Can Be Grouped into Superfamilies Based on Their Structures

The Glucose Transporter of Erythrocytes Mediates Passive Transport

The Chloride-Bicarbonate Exchanger Catalyzes Electroneutral Cotransport of Anions across the Plasma Membrane

Box 11-2 Defective Glucose and Water Transport In Two Forms of Diabetes

Active Transport Results in Solute Movement against a Concentration or Electrochemical Gradient

P-Type ATPases Undergo Phosphorylation during Their Catalytic Cycles

P-Type Ca 2＋ Pumps Maintain a Low Concentration of Calcium in the Cytosol

F-Type ATPases Are Reversible，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

Box 11-3 A Defective Ion Channel in Cystic Fibrosis

Aquaporins Form Hydrophilic Transmembrane Channels for the Passage of Water

Ion-Selective Channels Allow Rapid Movement of Ions across Membranes

Ion-Channel Function Is Measured Electrically

The Structure of a K＋ Channel Reveals the Basis for Its Specificity

The Neuronal Na＋ Channel Is a Voltage-Gated Ion Channel

The Acetylcholine Receptor Is a Ligand-Gated Ion Channel

Defective Ion Channels Can Have Adverse Physiological Consequences

12 Biosignaling

12.1 Molecular Mechanisms of Signal Transduction

Box 12-1 Scatchard Analysis Quantifies the Receptor-Ligand Interaction

12.2 Gated Ion Channels

Ion Channels Underlie Electrical Signaling in Excitable Cells

The Nicotinic Acetylcholine Receptor Is a Ligand-Gated Ion Channel

Voltage-Gated Ion Channels Produce Neuronal Action Potentials

Neurons Have Receptor Channels That Respond to Different Neurotransmitters

12.3 Receptor Enzymes

The Insulin Receptor Is a Tyrosine-Specific Protein Kinase

Receptor Guanylyl Cyclases Generate the Second Messenger cGMP

12.4 G Protein-Coupled Receptors and Second Messengers

The β-Adrenergic Receptor System Acts through the Second Messenger cAMP

The β-Adrenergic Receptor Is Desensitized by Phosphorylation

Cyclic AMP Acts as a Second Messenger for a Number of Regulatory Molecules

Two Second Messengers Are Derived from Phosphatidylinositols

Calcium Is a Second Messenger in Many Signal ansductions

Box 12-2 FRET：Biochemistry Visualized in a Living Cell

12.5 Multivalent Scaffold Proteins and Membrane Rafts

Protein Modules Bind Phosphorylated Tyr，Ser，or Thr Residues in Partner Proteins

Membrane Rafts and Caveolae May Segregate Signaling Proteins

12.6 Signaling in Microorganisms and Plants

Bacterial Signaling Entails Phosphorylation in a Two-Component System

Signaling Systems of Plants Have Some of the Same Components Used by Microbes and Mammals

Plants Detect Ethylene through a Two-Component System and a MAPK Cascade

Receptorlike Protein Kinases Transduce Signals from Peptides and Brassinosteroids

12.7 Sensory Transduction in Vision，Olfaction，and Gustation

Light Hyperpolarizes Rod and Cone Cells of the Vertebrate Eye

Light Triggers Conformational Changes in the Receptor Rhodopsin

Excited Rhodopsin Acts through the G Protein Transducin to Reduce the cGMP Concentration

Amplification of the Visual Signal Occurs in the Rod and Cone Cells

The Visual Signal Is Quickly Terminated

Rhodopsin Is Desensitized by Phosphorylation

Cone Cells Specialize in Color Vision

Vertebrate Olfaction and Gustation Use Mechanisms Similar to the Visual System

Box 12-3 Color Blindness：John Dalton’s Experiment from the Grave

G Protein-Coupled Serpentine Receptor Systems Share Several Features

Disruption of G-Protein Signaling Causes Disease

12.8 Regulation of Transcription by Steroid Hormones

12.9 Regulation of the Cell Cycle by Protein Kinases

The Cell Cycle Has Four Stages

Levels of Cyclin-Dependent Protein Kinases Oscillate

CDKs Regulate Cell Division by Phosphorylating Critical Proteins

12.10 Oncogenes，Tumor Suppressor Genes，and Programmed Cell Death

Oncogenes Are Mutant Forms of the Genes for Proteins That Regulate the Cell Cycle

Defects in Tumor Suppressor Genes Remove Normal Restraints on Cell Division

Apoptosis Is Programmed Cell Suicide

Ⅱ BIOENERGETICS AND METABOLISM

13 Principles of Bioenergetics

13.1 Bioenergetics and Thermodynamics

Biological Energy Transformations Obey the Laws of Thermodynamics

Cells Require Sources of Free Energy

The 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 Phosphoryl Group Transfers and ATP

The Free-Energy Change for ATP Hydrolysis Is Large and Negative

Other Phosphorylated Compounds and Thioesters Also Have Large Free Energies of Hydrolysis

Box 13-1 The Free Energy of Hydrolysis of ATP within Cells：The Real Cost of Doing Metabolic Business

ATP Provides Energy by Group Transfers，Not by Simple Hydrolysis

ATP Donates Phosphoryl，Pyrophosphoryl，and Adenylyl Groups

Box 13-2 Firefly Flashes：Glowing Reports of ATP

Assembly of Informational Macromolecules Requires Energy

ATP Energizes Active Transport and Muscle Contraction

Transphosphorylations between Nucleotides Occur in All Cell Types

Inorganic Polyphosphate Is a Potential Phosphoryl Group Donor

Biochemical and Chemical Equations Are Not Identical

13.3 Biological Oxidation-Reduction Reactions

The Flow of Electrons Can Do Biological Work

Oxidation-Reduction 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 the Free-Energy Change

Cellular Oxidation of Glucose to Carbon Dioxide Requires Specialized Electron Carriers

A Few Types of Coenzymes and Proteins Serve as Universal Electron Carriers

NADH and NADPH Act with Dehydrogenases as Soluble Electron Carriers

Dietary Deficiency of Niacin，the Vitamin Form of NAD and NADP，Causes Pellagra

Flavin Nucleotides Are Tightly Bound in Flavoproteins

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 Produces ATP and NADH

The Overall Balance Sheet Shows a Net Gain of ATP

Glycolysis Is under Tight Regulation

Cancerous Tissue Has Deranged Glucose Catabolism

14.2 Feeder Pathways for Glycolysis

Glycogen and Starch Are Degraded by Phosphorolysis

Dietary Polysaccharides and Disaccharides Undergo Hydrolysis to Monosaccharides

Other Monosaccharides Enter the Glycolytic Pathway at Several Points

14.3 Fates of Pyruvate under Anaerobic Conditions：Fermentation

Pyruvate Is the Terminal Electron Acceptor in Lactic Acid Fermentation

Ethanol Is the Reduced Product in Ethanol Fermentation

Box 14-1 Athletes，Alligators，and Coelacanths：Glycolysis at Limiting Concentrations of Oxygen

Thiamine Pyrophosphate Carries “Active Aldehyde”Groups

Fermentations Yield a Variety of Common Foods and Industrial Chemicals

Box 14-2 Brewing Beer

14.4 Gluconeogenesis

Conversion of Pyruvate to Phosphoenolpyruvate Requires Two Exergonic Reactions

Conversion of Fructose 1，6-Bisphosphate to Fructose 6-Phosphate Is the Second Bypass

Conversion of Glucose 6-Phosphate to Glucose Is the Third Bypass

Gluconeogenesis Is Energetically Expensive，But Essential

Citric Acid Cycle Intermediates and Many Amino Acids Are Glucogenic

Glycolysis and Gluconeogenesis Are Regulated Reciprocally

14.5 Pentose Phosphate Pathway of Glucose Oxidation

The Oxidative Phase Produces Pentose Phosphates and NADPH

Box 14-3 Why Pythagoras Wouldn’t Eat Falafel：Glucose6-Phosphate Dehydrogenase Deficiency

The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate

Wernicke-Korsakoff Syndrome Is Exacerbated by a Defect in Transketolase

Glucose 6-Phosphate Is Partitioned between Glycolysis and the Pentose Phosphate Pathway

15 Principles of Metabolic Regulation：Glucose and Glycogen

15.1 The Metabolism of Glycogen in Animals

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

Box 15-1 Carl and Gerty Cori：Pioneers in Glycogen Metabolism and Disease

Glycogenin Primes the Initial Sugar Residues in Glycogen

15.2 Regulation of Metabolic Pathways

Living Cells Maintain a Dynamic Steady State

Regulatory Mechanisms Evolved under Strong Selective Pressures

Regulatory Enzymes Respond to Changes in Metabolite Concentration

Enzyme Activity Can Be Altered in Several Ways

15.3 Coordinated Regulation of Glycolysis and Gluconeogenesis

Hexokinase Isozymes of Muscle and Liver Are Affected Differently by Their Product，Glucose 6-Phosphate

Box 15-2 Isozymes：Different Proteins That Catalyze the Same Reaction

Phosphofructokinase-1 Is under Complex Allosteric Regulation

Pyruvate Kinase Is Allosterically Inhibited by ATP

Gluconeogenesis Is Regulated at Several Steps

Fructose 2，6-Bisphosphate Is a Potent Regulator of Glycolysis and Gluconeogenesis

Are Substrate Cycles Futile？

Xylulose 5-Phosphate Is a Key Regulator of Carbohydrate and Fat Metabolism

15.4 Coordinated Regulation of Glycogen Synthesis and Breakdown

Glycogen Phosphorylase Is Regulated Allosterically and Hormonally

Glycogen Synthase Is Also Regulated by Phosphorylation and Dephosphorylation

Glycogen Synthase Kinase 3 Mediates the Actions of Insulin

Phosphoprotein Phosphatase 1 Is Central to Glycogen Metabolism

Transport into Cells Can Limit Glucose Utilization

Allosteric and Hormonal Signals Coordinate Carbohydrate Metabolism

Carbohydrate and Lipid Metabolism Are Integrated by Hormonal and Allosteric Mechanisms

Insulin Changes the Expression of Many Genes Involved in Carbohydrate and Fat Metabolism

15.5 Analysis of Metabolic Control

The Contribution of Each Enzyme to Flux through a Pathway Is Experimentally Measurable

The Control Coefficient Quantifies the Effect of a Change in Enzyme Activity on Metabolite Flux through a Pathway

The Elasticity Coefficient Is Related to an Enzyme’s Responsiveness to Changes in Metabolite or Regulator Concentrations

The Response Coefficient Expresses the Effect of an Outside Controller on Flux through a Pathway

Metabolic Control Analysis Has Been Applied to Carbohydrate Metabolism，with Surprising Results

Box 15-3 Metabolic Control Analysis：Quantitative Aspects

Metabolic Control Analysis Suggests a General Method for Increasing Flux through a Pathway

16 The Citric Acid Cycle

16.1 Production of Acetyl-CoA（Activated Acetate）

Pyruvate Is Oxidized to Acetyl-CoA and CO2

The Pyruvate Dehydrogenase Complex Requires Five Coenzymes

The Pyruvate Dehydrogenase Complex Consists of Three Distinct Enzymes

In Substrate Channeling，Intermediates Never Leave the Enzyme Surface

16.2 Reactions of the Citric Acid Cycle

The Citric Acid Cycle Has Eight Steps

Box 16-1 Synthases and Synthetases； Ligases and Lyases； Kinases，Phosphatases，and Phosphorylases：Yes，the Names Are Confusing！

The Energy of Oxidations in the Cycle Is Efficiently Conserved

Box 16-2 Citrate：A Symmetrical Molecule That Reacts Asymmetrically

Why Is the Oxidation of Acetate So Complicated？

Citric Acid Cycle Components Are Important Biosynthetic Intermediates

Anaplerotic Reactions Replenish Citric Acid Cycle Intermediates

Box 16-3 Citrate Synthase，Soda Pop，and the World Food Supply

Biotin in Pyruvate Carboxylase Carries CO2 Groups

16.3 Regulation of the Citric Acid Cycle

Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex Is Regulated by Allosteric and Covalent Mechanisms

The Citric Acid Cycle Is Regulated at Its Three Exergonic Steps

Substrate Channeling through Multienzyme Complexes May Occur in the Citric Acid Cycle

16.4 The Glyoxylate Cycle

The Glyoxylate Cycle Produces Four-Carbon Compounds from Acetate

The Citric Acid and Glyoxylate Cycles Are Coordinately Regulated

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

Box 17-1 Fat Bears Carry Out β Oxidation in Their Sleep

Complete Oxidation of Odd-Number Fatty Acids Requires Three Extra Reactions

Fatty Acid Oxidation Is Tightly Regulated

Genetic Defects in Fatty Acyl-CoA Dehydrogenases Cause Serious Disease

Box 17-2 Coenzyme B12：A Radical Solution to a Perplexing Problem

Peroxisomes Also Carry Out β Oxidation

Plant Peroxisomes and Glyoxysomes Use Acetyl-CoA from β Oxidation as a Biosynthetic Precursor

The β-Oxidation Enzymes of Different Organelles Have Diverged during Evolution

The ω Oxidation of Fatty Acids Occurs in the Endoplasmic Reticulum

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

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

Box 18-1 Assays for Tlssue Damage

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 Are Converted to Glucose，Others to Ketone Bodies

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 α-Ketoglutarate

Four Amino Acids Are Converted to Succinyl-CoA

Branched-Chain Amino Acids Are Not Degraded in the Liver

Box 18-2 Scientific Sleuths Solve a Murder Mystery

Asparagine and Aspartate Are Degraded to Oxaloacetate

19 Oxidative Phosphorylation and Photophosphorylation

OXIDATIVE PHOSPHORYLATION

19.1 Electron-Transfer Reactions in Mitochondria

Electrons Are Funneled to Universal Electron Acceptors

Electrons Pass through a Series of Membrane-Bound Carriers

Electron Carriers Function in Multienzyme Complexes

The Energy of Electron Transfer Is Efficiently Conserved in a Proton Gradient

Plant Mitochondria Have Alternative Mechanisms for Oxidizing NADH

19.2 ATP Synthesis

Box 19-1 Hot，Stinking Plants and Alternative Respiratory Pathways

ATP Synthase Has Two Functional Domains，Fo and F1

ATP Is Stabilized Relative to ADP on the Surface of F1

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 O2 Consumption and ATP Synthesis

The Proton-Motive Force Energizes Active Transport

Shuttle Systems Indirectly Convey Cytosolic NADH into Mitochondria for Oxidation

19.3 Regulation of Oxidative Phosphorylation

Oxidative Phosphorylation Is Regulated by Cellular Energy Needs

An Inhibitory Protein Prevents ATP Hydrolysis during Ischemia

Uncoupled Mitochondria in Brown Fat Produce Heat

ATP-Producing Pathways Are Coordinately Regulated

19.4 Mitochondrial Genes：Their Origin and the Effects of Mutations

Mutations in Mitochondrial Genes Cause Human Disease

Mitochondria Evolved from Endosymbiotic Bacteria

19.5 The Role of Mitochondria in Apoptosis and Oxidative Stress

PHOTOSYNTHESIS：HARVESTING LIGHT ENERGY

19.6 General Features of Photophosphorylation

Photosynthesis in Plants Takes Place in Chloroplasts

Light Drives Electron Flow in Chloroplasts

19.7 Light Absorption

Chlorophylls Absorb Light Energy for Photosynthesis

Accessory Pigments Extend the Range of Light Absorption

Chlorophyll Funnels the Absorbed Energy to Reaction Centers by Exciton Transfer

19.8 The Central Photochemical Event：Light-Driven Electron Flow

Bacteria Have One of Two Types of Single Photochemical Reaction Center

Kinetic and Thermodynamic Factors Prevent the Dissipation of Energy by Internal Conversion

In Plants，Two Reaction Centers Act in Tandem

Antenna Chlorophylls Are Tightly Integrated with Electron Carriers

Spatial Separation of Photosystems Ⅰ and Ⅱ Prevents Exciton Larceny

The Cytochrome b6 f Complex Links Photosystems Ⅱand Ⅰ

Cyanobacteria Use the Cytochrome b6 f Complex and Cytochrome c6 in Both Oxidative Phosphorylation and Photophosphorylation

Water Is Split by the Oxygen-Evolving Complex

19.9 ATP Synthesis by Photophosphorylation

A Proton Gradient Couples Electron Flow and Photophosphorylation

The Approximate Stoichiometry of Photophosphorylation Has Been Established

Cyclic Electron Flow Produces ATP but Not NADPH or O2

The ATP Synthase of Chloroplasts Is Like That of Mitochondria

Chloroplasts Evolved from Endosymbiotic Bacteria

Diverse Photosynthetic Organisms Use Hydrogen Donors Other Than Water

In Halophilic Bacteria，a Single Protein Absorbs Light and Pumps Protons to Drive ATP Synthesis

20 Carbohydrate Biosynthesis in Plants and Bacteria

20.1 Photosynthetic Carbohydrate Synthesis

Plastids Are Organelles Unique to Plant Cells and Algae

Carbon Dioxide Assimilation Occurs in Three Stages

Synthesis of Each Triose Phosphate from CO2 Requires Six NADPH and Nine ATP

A Transport System Exports Triose Phosphates from the Chloroplast and Imports Phosphate

Four Enzymes of the Calvin Cycle Are Indirectly Activated by Light

20.2 Photorespiration and the C4 and CAM Pathways

Photorespiration Results from Rubisco’s Oxygenase Activity

The Salvage of Phosphoglycolate Is Costly

In C4 Plants，CO2 Fixation and Rubisco Activity Are Spatially Separated

In CAM Plants，CO2 Capture and Rubisco Action Are Temporally Separated

20.3 Biosynthesis of Starch and Sucrose

ADP-Glucose Is the Substrate for Starch Synthesis in Plant Plastids and for Glycogen Synthesis in Bacteria

UDP-Glucose Is the Substrate for Sucrose Synthesis in the Cytosol of Leaf Cells

Conversion of Triose Phosphates to Sucrose and Starch Is Tightly Regulated

20.4 Synthesis of Cell Wall Polysaccharides：Plant Cellulose and Bacterial Peptidoglycan

Cellulose Is Synthesized by Supramolecular Structures in the Plasma Membrane

Lipid-Linked Oligosaccharides Are Precursors for Bacterial Cell Wall Synthesis

Box 20-1 The Magic Bullet versus the Bulletproof Vest：Penicillin and β-Lactamase

20.5 Integration of Carbohydrate Metabolism in the Plant Cell

Gluconeogenesis Converts Fats and Proteins to Glucose in Germinating Seeds

Pools of Common Intermediates Link Pathways in Different Organelles

21 Lipid Biosynthesis

21.1 Biosynthesis of Fatty Aclds and Eicosanoids

Malonyl-CoA Is Formed from Acetyl-CoA and Bicarbonate

Fatty Acid Synthesis Proceeds in a Repeating Reaction Sequence

The Fatty Acid Synthase Complex Has Seven Different Active Sites

Fatty Acid Synthase Receives the Acetyl and Malonyl Groups

The Fatty Acid Synthase Reactions Are Repeated to Form Palmitate

The Fatty Acid Synthase of Some Organisms Consists of Multifunctional Proteins

Fatty Acid Synthesis Occurs in the Cytosol of Many Organisms but in the Chloroplasts of Plants

Acetate Is Shuttled out of Mitochondria as Citrate

Fatty Acid Biosynthesis Is Tightly Regulated

Long-Chain Saturated Fatty Acids Are Synthesized from Palmitate

Desaturation of Fatty Acids Requires a Mixed-Function Oxidase

Box 21-1 Mixed-Function Oxidases，Oxygenases，and Cytochrome P-450

Eicosanoids Are Formed from 20-Carbon Polyunsaturated Fatty Acids

Box 21-2 Rellef Is in（the Active） Site：Cyclooxygenase Isozymes and the Search for a Better Aspirin

21.2 Biosynthesis of Triacylglycerols

Triacylglycerols and Glycerophospholipids Are Synthesized from the Same Precursors

Triacylglycerol Biosynthesis in Animals Is Regulated by Hormones

Adipose Tissue Generates Glycerol 3-phosphate by Glyceroneogenesis

21.3 Biosynthesis of Membrane Phospholipids

Cells Have Two Strategies for Attaching Phospholipid Head Groups

Phospholipid Synthesis in E.coli Employs CDP-Diacylglycerol

Eukaryotes Synthesize Anionic Phospholipids from CDP-Diacylglycerol

Eukaryotic Pathways to Phosphatidylserine，Phosphatidylethanolamine，and Phosphatidylcholine Are Interrelated

Plasmalogen Synthesis Requires Formation of an Ether-Linked Fatty Alcohol

Sphingolipid and Glycerophospholipid Synthesis Share Precursors and Some Mechanisms

Polar Lipids Are Targeted to Specific Cellular Membranes

21.4 Biosynthesis of Cholesterol，Steroids，and Isoprenoids

Cholesterol Is Made from Acetyl-CoA in Four Stages

Cholesterol Has Several Fates

Cholesterol and Other Lipids Are Carried on Plasma Lipoproteins

Box 21-3 ApoE Alleles Predict Incidence of Alzheimer’s Disease

Cholesteryl Esters Enter Cells by Receptor-Mediated Endocytosis

Cholesterol Biosynthesis Is Regulated at Several Levels

Steroid Hormones Are Formed by Side-Chain Cleavage and Oxidation of Cholesterol

Intermediates in Cholesterol Biosynthesis Have Many Alternative Fates

22 Biosynthesis of Amino Acids，Nucleotides，and Related Molecules

22.1 Overview of Nitrogen Metabolism

The Nitrogen Cycle Maintains a Pool of Biologically Available Nitrogen

Nitrogen Is Fixed by Enzymes of the Nitrogenase Complex

Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine

Glutamine Synthetase Is a Primary Regulatory Point in Nitrogen Metabolism

Several Classes of Reactions Play Special Roles in the Biosynthesis of Amino Acids and Nucleotides

22.2 Biosynthesis of Amino Acids

α-Ketoglutarate Gives Rise to Glutamate，Glutamine，Proline，and Arginine

Serine，Glycine，and Cysteine Are Derived from 3-Phospho-glycerate

Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruvate

Chorismate Is a Key Intermediate in the Synthesis of Tryptophan，Phenylalanine，and Tyrosine

Histidine Biosynthesis Uses Precursors of Purine Biosynthesis

Amino Acid Biosynthesis Is under Allosteric Regulation

22.3 Molecules Derived from Amino Acids

Glycine Is a Precursor of Porphyrins

Heme Is the Source of Bile Pigments

Box 22-1 Biochemistry of Kings and Vampires

Amino Acids Are Precursors of Creatine and Glutathione

D-Amino Acids Are Found Primarily in Bacteria

Aromatic Amino Acids Are Precursors of Many Plant Substances

Biological Amines Are Products of Amino Acid Decarboxylation

Arginine Is the Precursor for Biological Synthesis of Nitric Oxide

Box 22-2 Curing African Sleeping Sickness with a Blochemical Trojan Horse

22.4 Biosynthesis and Degradation of Nucleotides

De Novo Purine Nucleotide Synthesis Begins with PRPP

Purine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition

Pyrimidine Nucleotides Are Made from Aspartate，PRPP，and Carbamoyl Phosphate

Pyrimidine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition

Nucleoside Monophosphates Are Converted to Nucleoside Triphosphates

Ribonucleotides Are the Precursors of Deoxyribonucleotides

Thymidylate Is Derived from dCDP and dUMP

Degradation of Purines and Pyrimidines Produces Uric Acid and Urea，Respectively

Purine and Pyrimidine Bases Are Recycled by Salvage Pathways

Excess Uric Acid Causes Gout

Many Chemotherapeutic Agents Target Enzymes in the Nucleotide Biosynthetic Pathways

23 Hormonal Regulation and Integration of Mammalian Metabolism

23.1 Hormones：Diverse Structures for Diverse Functions

The Discovery and Purification of Hormones Require a Bioassay

Box 23-1 How Is a Hormone Discovered？The Arduous Path to Purified Insulin

Hormones Act through Specific High-Affinity Cellular Receptors

Hormones Are Chemically Diverse

Hormone Release Is Regulated by a Hierarchy of Neuronal and Hormonal Signals

23.2 Tissue-Specific Metabolism：The Division of Labor

The Liver Processes and Distributes Nutrients

Adipose Tissue Stores and Supplies Fatty Acids

Muscles Use ATP for Mechanical Work

The Brain Uses Energy for Transmission of Electrical Impulses

Blood Carries Oxygen，Metabolites，and Hormones

23.3 Hormonal Regulation of Fuel Metabolism

The Pancreas Secretes Insulin or Glucagon in Response to Changes in Blood Glucose

Insulin Counters High Blood Glucose

Glucagon Counters Low Blood Glucose

During Fasting and Starvation，Metabolism Shifts to Provide Fuel for the Brain

Epinephrine Signals Impending Activity

Cortisol Signals Stress，Including Low Blood Glucose

Diabetes Mellitus Arises from Defects in Insulin Production or Action

23.4 Obesity and the Regulation of Body Mass

The Lipostat Theory Predicts the Feedback Regulation of Adipose Tissue

Leptin Stimulates Production of Anorexigenic Peptide Hormones

Leptin Triggers a Signaling Cascade That Regulates Gene Expression

The Leptin System May Have Evolved to Regulate the Starvation Response

Insulin Acts in the Arcuate Nucleus to Regulate Eating and Energy Conservation

Adiponectin Acts through AMPK

Diet Regulates the Expression of Genes Central to Maintaining Body Mass

Short-Term Eating Behavior Is Set by Ghrelin and PYY3-36

Ⅲ INFORMATION PATHWAYS

24 Genes and Chromosomes

24.1 Chromosomal Elements

Genes Are Segments of DNA That Code for Polypeptide Chains and RNAs

DNA Molecules Are Much Longer Than the Cellular Packages That Contain Them

Eukaryotic Genes and Chromosomes Are Very Complex

24.2 DNA Supercoiling

Most Cellular DNA Is Underwound

DNA Underwinding Is Defined by Topological Linking Number

Topoisomerases Catalyze Changes in the Linking Number of DNA

DNA Compaction Requires a Special Form of Supercoiling

24.3 The Structure of Chromosomes

Chromatin Consists of DNA and Proteins

Histones Are Small，Basic Proteins

Nucleosomes Are the Fundamental Organizational Units of Chromatin

Nucleosomes Are Packed into Successively Higher Order Structures

Condensed Chromosome Structures Are Maintained by SMC Proteins

Bacterial DNA Is Also Highly Organized

25 DNA Metabolism

25.1 DNA Replication

DNA Replication Follows a Set of Fundamental Rules

DNA Is Degraded by Nucleases

DNA Is Synthesized by DNA Polymerases

Replication Is Very Accurate

E.coli Has at Least Five DNA Polymerases

DNA Replication Requires Many Enzymes and Protein Factors

Replication of the E.coli Chromosome Proceeds in Stages

Bacterial Replication Is Organized in Membrane-Bound Replication Factories

Replication in Eukaryotic Cells Is More Complex

25.2 DNA Repair

Mutations Are Linked to Cancer

All Cells Have Multiple DNA Repair Systems

Box 25-1 DNA Repair and Cancer

The Interaction of Replication Forks with DNA Damage Can Lead to Error-Prone Translesion DNA Synthesis

25.3 DNA Recombination

Homologous Genetic Recombination Has Several Functions

Recombination during Meiosis Is Initiated with Double-Strand Breaks

Recombination Requires a Host of Enzymes and Other Proteins

All Aspects of DNA Metabolism Come Together to Repair Stalled Replication Forks

Site-Specific Recombination Results in Precise DNA Rearrangements

Complete Chromosome Replication Can Require Site-Specific Recombination

Transposable Genetic Elements Move from One Locationto Another

Immunoglobulin Genes Assemble by Recombination

26 RNA Metabolism

26.1 DNA-Dependent Synthesis of RNA

RNA Is Synthesized by RNA Polymerases

RNA Synthesis Begins at Promoters

Transcription Is Regulated at Several Levels

Specific Sequences Signal Termination of RNA Synthesis

Box 26-1 RNA Polymerase Leaves Its Footprint on a Promoter

Eukaryotic Cells Have Three Kinds of Nuclear RNA Polymerases

RNA Polymerase Ⅱ Requires Many Other Protein Factors for Its Activity

DNA-Dependent RNA Polymerase Undergoes Selective Inhibition

26.2 RNA Processing

Eukaryotic mRNAs Are Capped at the 5’ End

Both Introns and Exons Are Transcribed from DNA into RNA

RNA Catalyzes the Splicing of Introns

Eukaryotic mRNAs Have a Distinctive 3’ End Structure

A Gene Can Give Rise to Multiple Products by Differential RNA Processing

Ribosomal RNAs and tRNAs Also Undergo Processing

RNA Enzymes Are the Catalysts of Some Events in RNA Metabolism

Cellular mRNAs Are Degraded at Different Rates

Polynucleotide Phosphorylase Makes Random RNA-like Polymers

26.3 RNA-Dependent Synthesis of RNA and DNA

Reverse Transcriptase Produces DNA from Viral RNA

Some Retroviruses Cause Cancer and AIDS

Many Transposons，Retroviruses，and Introns May Have a Common Evolutionary Origin

Box 26-2 Fighting AIDS with Inhibitors of HIV Reverse Transcriptase

Telomerase Is a Specialized Reverse Transcriptase

Some Viral RNAs Are Replicated by RNA-Dependent RNA Polymerase

RNA Synthesis Offers Important Clues to Biochemical Evolution

Box 26-3 The SELEX Method for Generating RNA Polymers with New Functions

27 Protein Metabolism

27.1 The Genetic Code

The Genetic Code Was Cracked Using Artificial mRNA Templates

Wobble Allows Some tRNAs to Recognize More than One Codon

Box 27-1 Changing Horses in Midstream：Translational Frameshifting and mRNA Editing

Box 27-2 Exceptions That Prove the Rule：Natural Variations in the Genetic Code

27.2 Protein Synthesis

Protein Biosynthesis Takes Place in Five Stages

The Ribosome Is a Complex Supramolecular Machine

Box 27-3 From an RNA World to a Protein World

Transfer RNAs Have Characteristic Structural Features

Stage 1：Aminoacyl-tRNA Synthetases Attach the Correct Amino Acids to Their tRNAs

Stage 2：A Specific Amino Acid Initiates Protein Synthesis

Stage 3：Peptide Bonds Are Formed in the Elongation Stage

Stage 4：Termination of Polypeptide Synthesis Requires a Special Signal

Stage 5：Newly Synthesized Polypeptide Chains Undergo Folding and Processing

Box 27-4 Induced Variation in the Genetic Code：Nonsense Suppression

Protein Synthesis Is Inhibited by Many Antibiotics and Toxins

27.3 Protein Targeting and Degradation

Posttranslational Modification of Many Eukaryotic Proteins Begins in the Endoplasmic Reticulum

Glycosylation Plays a Key Role in Protein Targeting

Signal Sequences for Nuclear Transport Are Not Cleaved

Bacteria Also Use Signal Sequences for Protein Targeting

Cells Import Proteins by Receptor-Mediated Endocytosis

Protein Degradation Is Mediated by Specialized Systems in All Cells

28 Regulation of Gene Expression

28.1 Principles of Gene Regulation

RNA Polymerase Binds to DNA at Promoters

Transcription Initiation Is Regulated by Proteins That Bind to or Near Promoters

Many Prokaryotic Genes Are Clustered and Regulated in Operons

The lac Operon Is Subject to Negative Regulation

Regulatory Proteins Have Discrete DNA-Binding Domains

Regulatory Proteins Also Have Protein-Protein Interaction Domains

28.2 Regulation of Gene Expression in Prokaryotes

The lac Operon Undergoes Positive Regulation

Many Genes for Amino Acid Biosynthetic Enzymes Are Regulated by Transcription Attenuation

Induction of the SOS Response Requires Destruction of Repressor Proteins

Synthesis of Ribosomal Proteins Is Coordinated with rRNA Synthesis

Some Genes Are Regulated by Genetic Recombination

28.3 Regulation of Gene Expression in Eukaryotes

Transcriptionally Active Chromatin Is Structurally Distinct from Inactive Chromatin

Chromatin Is Remodeled by Acetylation and Nucleosomal Displacements

Many Eukaryotic Promoters Are Positively Regulated

DNA-Binding Transactivators and Coactivators Facilitate Assembly of the General Transcription Factors

The Genes of Galactose Metabolism in Yeast Are Subject to Both Positive and Negative Regulation

DNA-Binding Transactivators Have a Modular Structure

Eukaryotic Gene Expression Can Be Regulated by Intercellular and Intracellular Signals

Regulation Can Result from Phosphorylation of Nuclear Transcription Factors

Many Eukaryotic mRNAs Are Subject to Translational Repression

Posttranscriptional Gene Silencing Is Mediated by RNA Interference

Development Is Controlled by Cascades of Regulatory Proteins