Biochemistry: A Short Course

by Tymoczko, John L.; Berg, Jeremy M.; Gatto, Jr., Gregory J.; Stryer, Lubert

• ISBN13: 9781319114633
• ISBN10: 1319114636
• eBook ISBN(s): 9781319234379
• Additional ISBN(s): 9781464126130
• Edition: 4th
• Format: Paperback
• Copyright: 2018-12-28
• Publisher: W. H. Freeman
• More Book Details

Summary

Derived from the classic text originated by Lubert Stryer and continued by John Tymoczko and Jeremy Berg, Biochemistry: A Short Course focuses on the major topics taught in a one-semester biochemistry course. With its brief chapters and relevant examples, this thoroughly updated new fourth edition helps students see the connections between the biochemistry they are studying and their own lives. This edition introduces an integrated multimedia program and tools and resources for active learning, in addition to extensive problem solving tools.

Biochemistry: A Short Course is now supported in Achieve, Macmillan’s new online learning platform. Achieve is the culmination of years of development work put toward creating the most powerful online learning tool for chemistry students. Achieve includes an interactive eBook as well as our renowned assessments and innovative, interactive Metabolic Map. Students will be able to focus their study with adaptive quizzing and more clearly see the relevance of chemistry through case studies. Instructor resources, including tools for active learning are all housed in this exciting new platform.

Achieve features a flexible suite of resources to support learning core concepts, visualization, problem-solving, and assessment. This powerful platform houses all student and instructor resources. You can assign what you want or download resources as you need. Powerful analytics and quick insights in Achieve pair with exceptional content to provide an unrivaled learning and teaching experience.

Table of Contents

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