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PART I: INTRODUCTION. Chapter 1. Introduction to the Chemistry of Life. 1. The Origin of Life       A. Biological Molecules Arose from Inorganic Materials       B. Complex Self–replicating Systems Evolved from Simple Molecules 2. Cellular Architecture       A. Cells Evolved to Carry Out Metabolic Reactions       B. There Are Two Types of Cells: Prokaryotes and Eukaryotes       C. Molecular Data Reveal Three Evolutionary Domains of Organisms       D. Organisms Continue to Evolve 3. Thermodynamics       A. The First Law of Thermodynamics States that Energy Is Conserved       B. The Second Law of Thermodynamics States that Entropy Tends to Increase       C. The Free Energy Change Determines the Spontaneity of a Process       D. Free Energy Changes Can Be Calculated from Equilibrium Concentrations       E. Life Obeys the Laws of Thermodynamics Box 1–1 Pathways of Discovery Lynn Margulis and the Theory of Endosymbiosis Box 1–2 Perspectives in Biochemistry Biochemical Conventions Chapter 2. Water. 1. Physical Properties of Water    A. Water Is a Polar Molecule    B. Hydrophilic Substances Dissolve in Water    C. The Hydrophobic Effect Causes Nonpolar Substances to Aggregate in Water    D. Water Moves by Osmosis and Solutes Move by Diffusion 2. Chemical Properties of Water    A. Water Ionizes to Form H+ and OH–    B. Acids and Bases Alter the pH    C. Buffers Resist Changes in pH Box 2–1 Biochemistry in Health and Disease The Blood Buffering System PART II: BIOMOLECULES. Chapter 3. Nucleotides, Nucleic Acids, and Genetic Information. 1. Nucleotides 2. Introduction to Nucleic Acid Structure    A. Nucleic Acids Are Polymers of Nucleotides    B. The DNA Forms a Double Helix    C. RNA Is a Single–Stranded Nucleic Acid 3. Overview of Nucleic Acid Function    A. DNA Carries Genetic Information    B. Genes Direct Protein Synthesis 4. Nucleic Acid Sequencing    A. Restriction Endonucleases Cleave DNA at Specific Sequences    B. Electrophoresis Separates Nucleic Acids According to Size    C. DNA Is Sequenced by the Chain–Terminator Method    D. Entire Genomes Have Been Sequenced    E. Evolution Results from Sequence Mutations 5. Manipulating DNA    A. Cloned DNA Is an Amplified Copy    B. DNA Libraries Are Collections of Cloned DNA    C. DNA Is Amplified by the Polymerase Chain Reaction    D. Recombinant DNA Technology Has Numerous Practical Applications Box 3–1 Pathways of Discovery Francis Collins and the Gene for Cystic Fibrosis Box 3–2 Perspectives in Biochemistry DNA Fingerprinting Box 3–3 Perspectives in Biochemistry Ethical Aspects of Recombinant DNA Technology Chapter 4. Amino Acids. 1. Amino Acid Structure    A. Amino Acids Are Dipolar Ions    B. Peptide Bonds Link Amino Acids    C. Amino Acid Side Chains Are Nonpolar, Polar, or Charged    D. The pK Values of Ionizable Groups Depend on Nearby Groups    E. Amino Acid Names Are Abbreviated 2. Stereochemistry 3. Amino Acid Derivatives    A. Protein Side Chains May be Modified    B. Some Amino Acids Are Biologically Active Box 4–1 Pathways of Discovery William C. Rose and the Discovery of Threonine Box 4–2 Perspectives in Biochemistry The RS System Box 4–3 Perspectives in Biochemistry Green Fluorescent Protein Chapter 5. Proteins: Primary Structure. 1. Polypeptide Diversity 2. Protein Purification and Analysis    A. Purifying a Protein Requires a Strategy    B. Salting Out Separates Proteins by Their Solubility    C. Chromatography Involves Interaction with Mobile and Stationary Phases    D. Electrophoresis Separates Molecules According to Charge and Size 3. Protein Sequencing    A. The First Step Is to Separate Subunits    B.  The Polypeptide Chains Are Cleaved    C. Edman Degradation Removes a Peptide’s First Amino Acid Residue    D. Mass Spectrometry Determines the Molecular Masses of Peptides    E. Reconstructed Protein Sequences Are Stored in Databases 4. Protein Evolution    A. Protein Sequences Reveal Evolutionary Relationships    B. Proteins Evolve by the Duplication of Genes or Gene Segments Box 5–1 Pathways of Discovery Frederick Sanger and Protein Sequencing Chapter 6. Proteins: Three–Dimensional Structure. 1. Secondary Structure    A. The Planar Peptide Group Limits Polypeptide Conformations    B. The Most Common Regular Secondary Structures Are the a Helix and the ß Sheet    C. Fibrous Proteins Have Repeating Secondary Structures    D. Most Proteins Include Nonrepetitive Structure 2. Tertiary Structure    A. Most Protein Structures Have Been Determined by X–Ray Crystallography or Nuclear Magnetic Resonance    B. Side Chain Location Varies with Polarity    C. Tertiary Structures Contain Combinations of Secondary Structure    D. Structure Is Conserved More than Sequence    E. Structural Bioinformatics Provides Tools for Storing, Visualizing, and Comparing Protein Structural Information 3. Quaternary Structure and Symmetry 4. Protein Stability    A. Proteins Are Stabilized by Several Forces    B. Proteins Can Undergo Denaturation and Renaturation 5. Protein Folding    A. Proteins Follow Folding Pathways    B. Molecular Chaperones Assist Protein Folding    C. Some Diseases Are Caused by Protein Misfolding Box 6–1 Pathways of Discovery Linus Pauling and Structural Biochemistry Box 6–2 Biochemistry in Health and Disease Collagen Diseases Box 6–3 Perspectives in Biochemistry Thermostable Proteins Box 6–4 Perspectives in Biochemistry Protein Structure Prediction and Protein Design Chapter 7. Protein Function: Myoglobin and Hemoglobin, Muscle Contraction, and Antibodies 1. Oxygen Binding to Myoglobin and Hemoglobin    A. Myoglobin Is a Monomeric Oxygen–Binding Protein    B.  Hemoglobin Is a Tetramer with Two Conformations    C. Oxygen Binds Cooperatively to Hemoglobin    D.  Hemoglobin’s Two Conformations Exhibit Different Affinities for Oxygen    E. Mutations May Alter Hemoglobin’s Structure and Function 2. Muscle Contraction    A.  Muscle Consists of Interdigitated Thick and Thin Filaments    B.  Muscle Contraction Occurs When Myosin Heads Walk Up Thin Filaments    C.  Actin Forms Microfilaments in Nonmuscle Cells 3. Antibodies    A.  Antibodies Have Constant and Variable Regions    B.  Antibodies Recognize a Huge Variety of Antigens Box 7–1 Perspectives in Biochemistry Other Oxygen–Transport Proteins Box 7–2 Pathways of Discovery Max Perutz and the Structure and Function of Hemoglobin Box 7–3 Biochemistry in Health and Disease High–Altitude Adaptation Box 7–4 Pathways of Discovery Hugh Huxley and the Sliding Filament Model Box 7–5 Perspectives in Biochemistry Monoclonal Antibodies Chapter 8. Carbohydrates. 1. Monosaccharides    A. Monosaccharides Are Aldoses or Ketoses    B. Monosaccharides Vary in Configuration and Conformation    C. Sugars Can Be Modified and Covalently Linked 2. Polysaccharides    A. Lactose and Sucrose Are Disaccharides    B. Cellulose and Chitin Are Structural Polysaccharides    C. Starch and Glycogen Are Storage Polysaccharides    D. Glycosaminoglycans Form Highly Hydrated Gels 3. Glycoproteins    A. Proteoglycans Contain Glycosaminoglycans    B. Bacterial Cell Walls Are Made of Peptidoglycan    C. Many Eukaryotic Proteins Are Glycosylated    D. Oligosaccharides May Determine Glycoprotein Structure, Function, and Recognition Box 8–1 Biochemistry in Health and Disease Lactose Intolerance Box 8–2 Perspectives in Biochemistry Artificial Sweeteners Box 8–3 Biochemistry in Health and Disease Peptidoglycan–Specific Antibiotics Chapter 9. Lipids and Biological Membranes. 1. Lipid Classification    A. The Properties of Fatty Acids Depend on Their Hydrocarbon Chains    B. Triacylglycerols Contain Three Esterified Fatty Acids    C. Glycerophospholipids Are Amphiphilic    D. Sphingolipids Are Amino Alcohol Derivatives    E. Steroids Contain Four Fused Rings    F. Other Lipids Perform a Variety of Metabolic Roles 2. Lipid Bilayers    A. Bilayer Formation Is Driven by the Hydrophobic Effect    B. Lipid Bilayers Have Fluidlike Properties 3. Membrane Proteins    A. Integral Membrane Proteins Interact with Hydrophobic Lipids    B. Lipid–Linked Proteins Are Anchored to the Bilayer    C. Peripheral Proteins Associate Loosely with Membranes 4. Membrane Structure and Assembly    A. The Fluid Mosaic Model Accounts for Lateral Diffusion    B. The Membrane Skeleton Helps Define Cell Shape    C. Membrane Lipids Are Distributed Asymmetrically    D. The Secretory Pathway Generates Secreted and Transmembrane Proteins    E. Intracellular Vesicles Transport Proteins    F. Proteins Mediate Vesicle Fusion Box 9–1 Biochemistry in Health and Disease Lung Surfactant Box 9–2 Pathways of Discovery Richard Henderson and the Structure of Bacteriorhodopsin Box 9–3 Biochemistry in Health and Disease Tetanus and Botulinum Toxins Specifically Cleave SNAREs Chapter 10. Membrane Transport. 1. Thermodynamics of Transport 2. Passive–Mediated Transport    A. Ionophores Carry Ions across Membranes    B. Porins Contain ? Barrels    C. Ion Channels Are Highly Selective    D. Aquaporins Mediate the Transmembrane Movement of Water    E. Transport Proteins Alternate between Two Conformations 3. Active Transport    A. The (Na+–K+)–ATPase Transports Ions in Opposite Directions    B. The Ca2+–ATPase Pumps Ca2+ out of the Cytosol    C. ABC Transporters Are Responsible for Drug Resistance    D. Active Transport May Be Driven by Ion Gradients Box 10–1 Perspectives in Biochemistry Gap Junctions Box 10–2 Perspectives in Biochemistry Differentiating Mediated and Nonmediated Transport Box 10–3 Biochemistry in Health and Disease The Action of Cardiac Glycosides PART III: ENZYMES. Chapter 11. Enzymatic Catalysis. 1. General Properties of Enzymes    A. Enzymes Are Classified by the Type of Reaction They Catalyze    B. Enzymes Act on Specific Substrates    C. Some Enzymes Require Cofactors 2. Activation Energy and the Reaction Coordinate 3. Catalytic Mechanisms    A. Acid–Base Catalysis Occurs by Proton Transfer    B. Covalent Catalysis Usually Requires a Nucleophile    C. Metal Ion Cofactors Act as Catalysts    D. Catalysis Can Occur through Proximity and Orientation Effects    E. Enzymes Catalyze Reactions by Preferentially Binding the Transition State 4. Lysozyme    A. Lysozyme’s Catalytic Site Was Identified through Model Building    B. The Lysozyme Reaction Proceeds via a Covalent Intermediate 5. Serine Proteases    A. The Active Site Residues Were Identified by Chemical Labeling    B. X–Ray Structures Provided Information about Catalysis, Substrate Specificity, and Evolution    C. Serine Proteases Use Several Catalytic Mechanisms    D. Zymogens Are Inactive Enzyme Precursors Box 11–1 Perspectives in Biochemistry Effects of pH on Enzyme Activity Box 11–2 Perspectives in Biochemistry Observing Enzyme Action by X–Ray Crystallography Box 11–3 Biochemistry in Health and Disease Nerve Poisons Box 11–4 Biochemistry in Health and Disease The Blood Coagulation Cascade Chapter 12. Enzyme Kinetics, Inhibition, and Control. 1. Reaction Kinetics    A. Chemical Kinetics Is Described by Rate Equations    B. Enzyme Kinetics Often Follows the Michaelis–Menten Equation    C. Kinetic Data Can Provide Values of Vmax and KM    D. Bisubstrate Reactions Follow One of Several Rate Equations 2. Enzyme Inhibition    A. Competitive Inhibition Involves Inhibitor Binding at an Enzyme’s Substrate Binding Site    B. Uncompetitive Inhibition Involves Inhibitor Binding to the Enzyme–Substrate Complex    C. Mixed Inhibition Involves Inhibitor Binding to Both the Free Enzyme and the Enzyme–Substrate Complex 3. Control of Enzyme Activity    A.  Allosteric Control Involves Binding at a Site Other Than the Active Site    B.  Control by Covalent Modification Often Involves Protein Phosphorylation 4. Drug Design    A. Drug Discovery Employs a Variety of Techniques    B. A Drug’s Bioavailability Depends on How It Is Absorbed and Transported in the Body    C. Clinical Trials Test for Efficacy and Safety    D. Cytochromes P450 Are Often Implicated in Adverse Drug Reactions Box 12–1 Perspectives in Biochemistry Isotopic Labeling Box 12–2 Pathways of Discovery J.B.S. Haldane and Enzyme Action Box 12–3 Perspectives in Biochemistry Kinetics and Transition State Theory Box 12–4 Biochemistry in Health and Disease HIV Enzyme Inhibitors Chapter 13. Biochemical Signaling 1. Hormones    A.  Pancreatic Islet Hormones Control Fuel Metabolism    B.  Epinephrine and Norepinephrine Prepare the Body for Action    C.  Steroid Hormones Regulate a Wide Variety of Metabolic and Sexual Processes    D.  Growth Hormone Binds to Receptors in Muscle, Bone, and Cartilage 2. Receptor Tyrosine Kinases    A.  Receptor Tyrosine Kinases Transmit Signals across the Cell Membrane    B.  Kinase Cascades Relay Signals to the Nucleus    C.  Some Receptors Are Associated with Nonreceptor Tyrosine Kinases    D.  Protein Phosphatases Are Signaling Proteins in Their Own Right 3. Heterotrimeric G Proteins    A.  G Protein–Coupled Receptors Contain Seven Transmembrane Helices    B.  Heterotrimeric G Proteins Dissociate on Activation    C.  Adenylate Cyclase Synthesizes cAMP to Activate Protein Kinase A    D.  Phosphodiesterases Limit Second Messenger Activity 4. The Phosphoinositide Pathway    A.  Ligand Binding Results in the Cytoplasmic Release of the Second Messengers IP3 and Ca2+    B.  Calmodulin Is a Ca2+–Activated Switch    C.  DAG Is a Lipid–Soluble Second Messenger that Activates Protein Kinase C    D.  Epilog: Complex Systems Have Emergent Properties Box 13–1 Pathways of Discovery Rosalyn Yalow and the Radioimmunoassay (RIA) Box 13–2 Perspectives in Biochemistry Receptor–Ligand Binding Can Be Quantitated Box 13–3 Biochemistry in Health and Disease Oncogenes and Cancer Box 13–4 Biochemistry in Health and Disease Drugs and Toxins That Affect Cell Signaling Box 13–5 Biochemistry in Health and Disease Anthrax PART IV: METABOLISM. Chapter 14. Introduction to Metabolism. 1. Overview of Metabolism    A.  Nutrition Involves Food Intake and Use    B.  Vitamins and Minerals Assist Metabolic Reactions    C. Metabolic Pathways Consist of Series of Enzymatic Reactions    D. Thermodynamics Dictates the Direction and Regulatory Capacity of Metabolic Pathways    E. Metabolic Flux Must Be Controlled 2. “High–Energy” Compounds    A. ATP Has a High Phosphoryl Group–Transfer Potential    B. Coupled Reactions Drive Endergonic Processes    C. Some Other Phosphorylated Compounds Have High Phosphoryl Group–Transfer Potentials    D. Thioesters Are Energy–Rich Compounds 3. Oxidation–Reduction Reactions    A. NAD+ and FAD Are Electron Carriers    B. The Nernst Equation Describes Oxidation–Reduction Reactions    C. Spontaneity Can Be Determined by Measuring Reduction Potential Differences 4. Experimental Approaches to the Study of Metabolism    A. Labeled Metabolites Can Be Traced    B. Studying Metabolic Pathways Often Involves Perturbing the System    C.  Systems Biology Has Entered the Study of Metabolism Box 14–1 Perspectives in Biochemistry Oxidation States of Carbon Box 14–2 Perspectives in Biochemistry Mapping Metabolic Pathways Box 14–3 Pathways of Discovery Fritz Lipmann and “High–energy” Compounds Box 14–4 Perspectives in Biochemistry ATP and DG Chapter 15. Glucose Catabolism. 1. Overview of Glycolysis 2. The Reactions of Glycolysis    A. Hexokinase Uses the First ATP    B. Phosphoglucose Isomerase Converts Glucose–6–Phosphate to Fructose–6–Phosphate    C. Phosphofructokinase Uses the Second ATP    D. Aldolase Converts a 6–Carbon Compound to Two 3–Carbon Compounds    E. Triose Phosphate Isomerase Interconverts Dihydroxyacetone Phosphate and Glyceraldehyde–3–Phosphate    F. Glyceraldehyde–3–Phosphate Dehydrogenase Forms the First “High–Energy” Intermediate    G. Phosphoglycerate Kinase Generates the First ATP    H. Phosphoglycerate Mutase Interconverts 3–Phosphoglycerate and 2–Phosphoglycerate    I. Enolase Forms the Second “High–Energy” Intermediate    J. Pyruvate Kinase Generates the Second ATP 3. Fermentation: The Anaerobic Fate of Pyruvate    A. Homolactic Fermentation Converts Pyruvate to Lactate    B. Alcoholic Fermentation Converts Pyruvate to Ethanol and CO2    C. Fermentation is Energetically Favorable 4. Regulation of Glycolysis    A.     Phosphofructokinase is The Major Flux–Controlling Enzyme of Glycolysis in Muscle    B. Substrate Cycling Fine–Tunes Flux Control 5. Metabolism of Hexoses Other than Glucose    A. Fructose Is Converted to F