Biochemistry: An Evolving Science

Chapter Introduction

ABOUT THE AUTHORS

PREFACE

MEDIA AND ASSESSMENT

MOLECULAR EVOLUTION

CLINICAL APPLICATIONS

ACKNOWLEDGMENTS

BRIEF CONTENTS

CONTENTS

Biochemistry: An Evolving Science

Chapter Introduction

1.1: Biochemical Unity Underlies Biological Diversity

1.2: DNA Illustrates the Interplay Between Form and Function

1.3: Concepts from Chemistry Explain the Properties of Biological Molecules

1.4: The Genomic Revolution Is Transforming Biochemistry, Medicine, and Other Fields

APPENDIX: Visualizing Molecular Structures I: Small Molecules

KEY TERMS

PROBLEMS

Protein Composition and Structure

Chapter Introduction

2.1: Proteins Are Built from a Repertoire of 20 Amino Acids

2.2: Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains

2.3: Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops

2.4: Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores

2.5: Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures

2.6: The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure

SUMMARY

APPENDIX: Visualizing Molecular Structures II: Proteins

KEY TERMS

PROBLEMS

Exploring Proteins and Proteomes

Chapter Introduction

3.1: The Purification of Proteins Is an Essential First Step in Understanding Their Function

3.2: Immunology Provides Important Techniques with Which to Investigate Proteins

3.3: Mass Spectrometry is a Powerful Technique for the Identification of Peptides and Proteins

3.4: Peptides Can Be Synthesized by Automated Solid-Phase Methods

3.5: Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography and NMR Spectroscopy

SUMMARY

KEY TERMS

PROBLEMS

DNA, RNA, and the Flow of Genetic Information

Chapter Introduction

4.1: A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar-Phosphate Backbone

4.2: A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure

4.3: The Double Helix Facilitates the Accurate Transmission of Hereditary Information

4.4: DNA Is Replicated by Polymerases That Take Instructions from Templates

4.5: Gene Expression Is the Transformation of DNA Information into Functional Molecules

4.6: Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point

4.7: Most Eukaryotic Genes Are Mosaics of Introns and Exons

SUMMARY

KEY TERMS

PROBLEMS

Exploring Genes and Genomes

Chapter Introduction

5.1: The Exploration of Genes Relies on Key Tools

5.2: Recombinant DNA Technology Has Revolutionized All Aspects of Biology

5.3: Complete Genomes Have Been Sequenced and Analyzed

5.4: Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision

SUMMARY

KEY TERMS

PROBLEMS

Exploring Evolution and Bioinformatics

Chapter Introduction

6.1: Homologs Are Descended from a Common Ancestor

6.2: Statistical Analysis of Sequence Alignments Can Detect Homology

6.3: Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships

6.4: Evolutionary Trees Can Be Constructed on the Basis of Sequence Information

6.5: Modern Techniques Make the Experimental Exploration of Evolution Possible

SUMMARY

KEY TERMS

PROBLEMS

Hemoglobin: Portrait of a Protein in Action

Chapter Introduction

7.1: Myoglobin and Hemoglobin Bind Oxygen at Iron Atoms in Heme

7.2: Hemoglobin Binds Oxygen Cooperatively

7.3: Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen: The Bohr Effect

7.4: Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease

SUMMARY

APPENDIX: Binding Models Can Be Formulated in Quantitative Terms: The Hill Plot and the Concerted Model

KEY TERMS

PROBLEMS

Enzymes: Basic Concepts and Kinetics

Chapter Introduction

8.1: Enzymes Are Powerful and Highly Specific Catalysts

8.2: Gibbs Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes

8.3: Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State

8.4: The Michaelis-Menten Model Accounts for the Kinetic Properties of Many Enzymes

8.5: Enzymes Can Be Inhibited by Specific Molecules

8.6: Enzymes Can Be Studied One Molecule at a Time

SUMMARY

APPENDIX: Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze

KEY TERMS

PROBLEMS

Catalytic Strategies

Chapter Introduction

9.1 Proteases Facilitate a Fundamentally Difficult Reaction

9.2 Carbonic Anhydrases Make a Fast Reaction Faster

9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions

9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work

SUMMARY

KEY TERMS

PROBLEMS

Regulatory Strategies

Chapter Introduction

10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway

10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages

10.3 Covalent Modification Is a Means of Regulating Enzyme Activity

10.4 Many Enzymes are Activated by Specific Proteolytic Cleavage

SUMMARY

KEY TERMS

PROBLEMS

Carbohydrates

Chapter Introduction

11.1 Monosaccharides Are the Simplest Carbohydrates

11.2 Monosaccharides Are Linked to Form Complex Carbohydrates

11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins

11.4 Lectins Are Specific Carbohydrate-Binding Proteins

SUMMARY

KEY TERMS

PROBLEMS

Lipids and Cell Membranes

Chapter Introduction

12.1 Fatty Acids Are Key Constituents of Lipids

12.2 There Are Three Common Types of Membrane Lipids

12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media

12.4 Proteins Carry Out Most Membrane Processes

12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane

12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes

SUMMARY

KEY TERMS

PROBLEMS

Membrane Channels and Pumps

Chapter Introduction

13.1 The Transport of Molecules Across a Membrane May Be Active or Passive

13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes

13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another

13.4 Specific Channels Can Rapidly Transport Ions Across Membranes

13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells

13.6 Specific Channels Increase the Permeability of Some Membranes to Water

SUMMARY

KEY TERMS

PROBLEMS

Signal-Transduction Pathways

Chapter Introduction

14.1 Heterotrimeric G Proteins Transmit Signals and Reset Themselves

14.2 Insulin Signaling: Phosphorylation Cascades Are Central to Many Signal-Transduction Processes

14.3 EGF Signaling: Signal-Transduction Pathways Are Poised to Respond

14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways

14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases

SUMMARY

KEY TERMS

PROBLEMS

Metabolism: Basic Concepts and Design

Chapter Introduction

15.1 Metabolism Is Composed of Many Coupled, Interconnecting Reactions

15.2 ATP Is the Universal Currency of Free Energy in Biological Systems

15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy

15.4 Metabolic Pathways Contain Many Recurring Motifs

SUMMARY

KEY TERMS

PROBLEMS

Glycolysis and Gluconeogenesis

Chapter Introduction

16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms

16.2 The Glycolytic Pathway Is Tightly Controlled

16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors

16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated

SUMMARY

KEY TERMS

PROBLEMS

The Citric Acid Cycle

Chapter Introduction

17.1 The Pyruvate Dehydrogenase Complex Links Glycolysis to the Citric Acid Cycle

17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units

17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled

17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors

17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate

SUMMARY

KEY TERMS

PROBLEMS

Oxidative Phosphorylation

Chapter Introduction

18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria

18.2 Oxidative Phosphorylation Depends on Electron Transfer

18.3 The Respiratory Chain Consists of Four Complexes: Three Proton Pumps and a Physical Link to the Citric Acid Cycle

18.4 A Proton Gradient Powers the Synthesis of ATP

18.5 Many Shuttles Allow Movement Across Mitochondrial Membranes

18.6 The Regulation of Cellular Respiration Is Governed Primarily by the Need for ATP

SUMMARY

KEY TERMS

PROBLEMS

The Light Reactions of Photosynthesis

Chapter Introduction

19.1 Photosynthesis Takes Place in Chloroplasts

19.2 Light Absorption by Chlorophyll Induces Electron Transfer

19.3 Two Photosystems Generate a Proton Gradient and NADPH in Oxygenic Photosynthesis

19.4 A Proton Gradient across the Thylakoid Membrane Drives ATP Synthesis

19.5 Accessory Pigments Funnel Energy into Reaction Centers

19.6 The Ability to Convert Light into Chemical Energy Is Ancient

SUMMARY

KEY TERMS

PROBLEMS

The Calvin Cycle and the Pentose Phosphate Pathway

Chapter Introduction

20.1 The Calvin Cycle Synthesizes Hexoses from Carbon Dioxide and Water

20.2 The Activity of the Calvin Cycle Depends on Environmental Conditions

20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes Five-Carbon Sugars

20.4 The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis

20.5 Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species

SUMMARY

KEY TERMS

PROBLEMS

Glycogen Metabolism

Chapter Introduction

21.1 Glycogen Breakdown Requires the Interplay of Several Enzymes

21.2 Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation

21.3 Epinephrine and Glucagon Signal the Need for Glycogen Breakdown

21.4 Glycogen Is Synthesized and Degraded by Different Pathways

21.5 Glycogen Breakdown and Synthesis Are Reciprocally Regulated

SUMMARY

KEY TERMS

PROBLEMS

Fatty Acid Metabolism

Chapter Introduction

22.1 Triacylglycerols Are Highly Concentrated Energy Stores

22.2 The Use of Fatty Acids as Fuel Requires Three Stages of Processing

22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation

22.4 Fatty Acids Are Synthesized by Fatty Acid Synthase

22.5 The Elongation and Unsaturation of Fatty Acids Are Accomplished by Accessory Enzyme Systems

22.6 Acetyl CoA Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism

SUMMARY

KEY TERMS

PROBLEMS

Protein Turnover and Amino Acid Catabolism

Chapter Introduction

23.1 Proteins Are Degraded to Amino Acids

23.2 Protein Turnover Is Tightly Regulated

23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen

23.4 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates

23.5 Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates

23.6 Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation

SUMMARY

KEY TERMS

PROBLEMS

The Biosynthesis of Amino Acids

Chapter Introduction

24.1 Nitrogen Fixation: Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia

24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways

24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis

24.4 Amino Acids Are Precursors of Many Biomolecules

SUMMARY

KEY TERMS

PROBLEMS

Nucleotide Biosynthesis

Chapter Introduction

25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways

25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways

25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism

25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition

25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions

SUMMARY

KEY TERMS

PROBLEMS

The Biosynthesis of Membrane Lipids and Steroids

Chapter Introduction

26.1 Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols

26.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages

26.3 The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels

26.4 Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones

SUMMARY

KEY TERMS

PROBLEMS

The Integration of Metabolism

Chapter Introduction

27.1 Caloric Homeostasis Is a Means of Regulating Body Weight

27.2 The Brain Plays a Key Role in Caloric Homeostasis

27.3 Diabetes Is a Common Metabolic Disease Often Resulting from Obesity

27.4 Exercise Beneficially Alters the Biochemistry of Cells

27.5 Food Intake and Starvation Induce Metabolic Changes

27.6 Ethanol Alters Energy Metabolism in the Liver

SUMMARY

KEY TERMS

PROBLEMS

DNA Replication, Repair, and Recombination

Chapter Introduction

28.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template

28.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases

28.3 DNA Replication Is Highly Coordinated

28.4 Many Types of DNA Damage Can Be Repaired

28.5 DNA Recombination Plays Important Roles in Replication, Repair, and Other Processes

SUMMARY

KEY TERMS

PROBLEMS

RNA Synthesis and Processing

Chapter Introduction

29.1 RNA Polymerases Catalyze Transcription

29.2 Transcription in Eukaryotes Is Highly Regulated

29.3 The Transcription Products of Eukaryotic Polymerases Are Processed

29.4 The Discovery of Catalytic RNA Was Revealing in Regard to Both Mechanism and Evolution

SUMMARY

KEY TERMS

PROBLEMS

Protein Synthesis

Chapter Introduction

30.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences

30.2 Aminoacyl Transfer RNA Synthetases Read the Genetic Code

30.3 The Ribosome Is the Site of Protein Synthesis

30.4 Eukaryotic Protein Synthesis Differs from Bacterial Protein Synthesis Primarily in Translation Initiation

30.5 A Variety of Antibiotics and Toxins Can Inhibit Protein Synthesis

30.6 Ribosomes Bound to the Endoplasmic Reticulum Manufacture Secretory and Membrane Proteins

SUMMARY

KEY TERMS

PROBLEMS

The Control of Gene Expression in Prokaryotes

Chapter Introduction

31.1 Many DNA-Binding Proteins Recognize Specific DNA Sequences

31.2 Prokaryotic DNA-Binding Proteins Bind Specifically to Regulatory Sites in Operons

31.3 Regulatory Circuits Can Result in Switching Between Patterns of Gene Expression

31.4 Gene Expression Can Be Controlled at Posttranscriptional Levels

SUMMARY

KEY TERMS

PROBLEMS

The Control of Gene Expression in Eukaryotes

Chapter Introduction

32.1 Eukaryotic DNA Is Organized into Chromatin

32.2 Transcription Factors Bind DNA and Regulate Transcription Initiation

32.3 The Control of Gene Expression Can Require Chromatin Remodeling

32.4 Eukaryotic Gene Expression Can Be Controlled at Posttranscriptional Levels

SUMMARY

KEY TERMS

PROBLEMS

Sensory Systems

Chapter Introduction

33.1 A Wide Variety of Organic Compounds Are Detected by Olfaction

33.2 Taste Is a Combination of Senses That Function by Different Mechanisms

33.3 Photoreceptor Molecules in the Eye Detect Visible Light

33.4 Hearing Depends on the Speedy Detection of Mechanical Stimuli

33.5 Touch Includes the Sensing of Pressure, Temperature, and Other Factors

SUMMARY

KEY TERMS

PROBLEMS

The Immune System

Chapter Introduction

34.1 Antibodies Possess Distinct Antigen-Binding and Effector Units

34.2 Antibodies Bind Specific Molecules Through Hypervariable Loops

34.3 Diversity Is Generated by Gene Rearrangements

34.4 Major-Histocompatibility-Complex Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors

34.5 The Immune System Contributes to the Prevention and the Development of Human Diseases

SUMMARY

KEY TERMS

PROBLEMS

Molecular Motors

Chapter Introduction

35.1 Most Molecular-Motor Proteins Are Members of the P-Loop NTPase Superfamily

35.2 Myosins Move Along Actin Filaments

35.3 Kinesin and Dynein Move Along Microtubules

35.4 A Rotary Motor Drives Bacterial Motion

SUMMARY

KEY TERMS

PROBLEMS

Drug Development

Chapter Introduction

36.1 The Development of Drugs Presents Huge Challenges

36.2 Drug Candidates Can Be Discovered by Serendipity, Screening, or Design

36.3 Analyses of Genomes Hold Great Promise for Drug Discovery

36.4 The Clinical Development of Drugs Proceeds Through Several Phases

SUMMARY

KEY TERMS

PROBLEMS

Answer To Problems

Chapter 1

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7

Chapter 8

Chapter 9

Chapter 10

Chapter 11

Chapter 12

Chapter 13

Chapter 14

Chapter 15

Chapter 16

Chapter 17

Chapter 18

Chapter 19

Chapter 20

Chapter 21

Chapter 22

Chapter 23

Chapter 24

Chapter 25

Chapter 26

Chapter 27

Chapter 28

Chapter 29

Chapter 30

Chapter 31

Chapter 32

Chapter 33

Chapter 34

Chapter 35

Chapter 36

SELECTED READINGS

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7

Chapter 8

Chapter 9

Chapter 10

Chapter 11

Chapter 12

Chapter 13

Chapter 14

Chapter 15

Chapter 16

Chapter 17

Chapter 18

Chapter 19

Chapter 20

Chapter 21

Chapter 22

Chapter 23

Chapter 24

Chapter 25

Chapter 26

Chapter 27

Chapter 28

Chapter 29

Chapter 30

Chapter 31

Chapter 32

Chapter 33

Chapter 34

Chapter 35

Chapter 36

INDEX

Index

Endpaper

ACIDITY CONSTANTS

STANDARD BOND LENGTHS