Fundamentals of Biochemistry: Life at the Molecular Level

Front Cover
Title Page
Dedication
Copyright
About the Authors
Brief Contents
CONTENTS (with direct page links)
	PART I INTRODUCTION
	PART I I BIOMOLECULES
	PART I I I ENZYMES
	PART IV METABOLISM
	PART V GENE EXPRESSION AND REPLICATION
Preface
PART I - INTRODUCTION [1-2]
	1. Introduction to the Chemistry of Life
		1 The Origin of Life
			A. Biological Molecules Arose from Inanimate Substances
			B. Complex Self-Replicating Systems Evolved from Simple Molecules
		2 Cellular Architecture
			A. Cells 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 Reactant and Product Concentrations
			E. Life Achieves Homeostasis While Obeying the Laws of Thermodynamics
		Summary & Problems
		BOX 1-1 Pathways of Discovery Lynn Margulis and the Theory of Endosymbiosis
		BOX 1-2 Perspectives in Biochemistry Biochemical Conventions
	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
		Summary & Problems
		BOX 2-1 Perspectives in Biochemistry The Consequences of Ocean Acidification
		BOX 2-2 Biochemistry in Health and Disease The Blood Buffering System
PART II - BIOMOLECULES [3-10]
	3. Nucleotides, Nucleic Acids, and Genetic Information
		1 Nucleotides
		2 Introduction to Nucleic Acid Structure
			A. Nucleic Acids Are Polymers of Nucleotides
			B. 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. Traditional DNA Sequencing Uses the Chain-Terminator Method
			D. Next-Generation Sequencing Technologies Are Massively Parallel
			E. Entire Genomes Have Been Sequenced
			F. 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
		Summary & Problems
		BOX 3-1 Pathways to 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
	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
		Summary & Problems
		BOX 4-1 Pathways to 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
	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
			E. Ultracentrifugation Separates Macromolecules by Mass
		3 Protein Sequencing
			A. The First Step Is to Separate Subunits
			B. The Polypeptide Chains Are Cleaved
			C. Edman Degradation Removes a Peptide’s N-Terminal Amino Acid Residue
			D. Peptides Can Be Sequenced by Mass Spectrometry
			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
		Summary & Problems
		BOX 5-1 Pathways of Discovery Frederick Sanger and Protein Sequencing
	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 α Helix and the β Sheet
			C. Fibrous Proteins Have Repeating Secondary Structures
			D. Most Proteins Include Nonrepetitive Structure
		2 Tertiary Structure
			A. Protein Structures Are Determined by X-Ray Crystallography, Nuclear Magnetic Resonance, and Cryo-Electron Microscopy
			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
			C. Proteins Are Dynamic
		5 Protein Folding
			A. Proteins Follow Folding Pathways
			B. Molecular Chaperones Assist Protein Folding
			C. Many Diseases Are Caused by Protein Misfolding
		Summary & Problems
		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
	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
		Summary & Problems
		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
	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
		Summary & Problems
		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
	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
		Summary & Problems
		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
	10. Membrane Transport
		1 Thermodynamics of Transport
		2 Passive-Mediated Transport
			A. Ionophores Carry Ions across Membranes
			B. Porins Contain β 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
		Summary & Problems
		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 [11-13]
	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. Active Site Residues Were Identified by Chemical Labeling
			B. X-Ray Structures Provide Information about Catalysis, Substrate Specificity, and Evolution
			C. Serine Proteases Use Several Catalytic Mechanisms
			D. Zymogens Are Inactive Enzyme Precursors
		Summary & Problems
		BOX 11-1 Perspectives in Biochemistry Drawing Reaction Mechanisms
		BOX 11-2 Perspectives in Biochemistry Effects of pH on Enzyme Activity
		BOX 11-3 Biochemistry in Health and Disease Nerve Poisons
		BOX 11-4 Biochemistry in Health and Disease The Blood Coagulation Cascade
	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 Usually 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
		Summary & Problems
		BOX 12-1 Pathways of Discovery J.B.S. Haldane and Enzyme Action
		BOX 12-2 Perspectives in Biochemistry Kinetics and Transition State Theory
		BOX 12-3 Biochemistry in Health and Disease HIV Enzyme Inhibitors
	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
		Summary & Problems
		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
PART IV - METABOLISM [14-22]
	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
		Summary & Problems
		BOX 14-1 Perspectives in Biochemistry Oxidation States of Carbon
		BOX 14-2 Pathways of Discovery Fritz Lipmann and “High-Energy” Compounds
		BOX 14-3 Perspectives in Biochemistry ATP and ΔG
	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 Fructose-6-Phosphate or Glyceraldehyde-3-Phosphate
			B. Galactose Is Converted to Glucose-6-Phosphate
			C. Mannose Is Converted to Fructose-6-Phosphate
		6 The Pentose Phosphate Pathway
			A. Oxidative Reactions Produce NADPH in Stage 1
			B. Isomerization and Epimerization of Ribulose-5-Phosphate Occur in Stage 2
			C. Stage 3 Involves Carbon–Carbon Bond Cleavage and Formation
			D. The Pentose Phosphate Pathway Must Be Regulated
		Summary & Problems
		BOX 15-1 Pathways of Discovery Otto Warburg and Studies of Metabolism
		BOX 15-2 Perspectives in Biochemistry Synthesis of 2,3-Bisphosphoglycerate in Erythrocytes and Its Effect on the Oxygen Carrying Capacity of the Blood
		BOX 15-3 Perspectives in Biochemistry Glycolytic ATP Production in Muscle
		BOX 15-4 Biochemistry in Health and Disease Glucose-6-Phosphate Dehydrogenase Deficiency
	16. Glycogen Metabolism and Gluconeogenesis
		1 Glycogen Breakdown
			A. Glycogen Phosphorylase Degrades Glycogen to Glucose-1-Phosphate
			B. Glycogen Debranching Enzyme Acts as a Glucosyltransferase
			C. Phosphoglucomutase Interconverts Glucose-1-Phosphate and Glucose-6-Phosphate
		2 Glycogen Synthesis
			A. UDP–Glucose Pyrophosphorylase Activates Glucosyl Units
			B. Glycogen Synthase Extends Glycogen Chains
			C. Glycogen Branching Enzyme Transfers Seven-Residue Glycogen Segments
		3 Control of Glycogen Metabolism
			A. Glycogen Phosphorylase and Glycogen Synthase Are under Allosteric Control
			B. Glycogen Phosphorylase and Glycogen Synthase Undergo Control by Covalent Modification
			C. Glycogen Metabolism Is Subject to Hormonal Control
		4 Gluconeogenesis
			A. Pyruvate Is Converted to Phosphoenolpyruvate in Two Steps
			B. Hydrolytic Reactions Bypass Irreversible Glycolytic Reactions
			C. Gluconeogenesis and Glycolysis Are Independently Regulated
		5 Other Carbohydrate Biosynthetic Pathways
		Summary & Problems
		BOX 16-1 Pathways of Discovery Carl and Gerty Cori and Glucose Metabolism
		BOX 16-2 Biochemistry in Health and Disease Glycogen Storage Diseases
		BOX 16-3 Perspectives in Biochemistry Optimizing Glycogen Structure
		BOX 16-4 Perspectives in Biochemistry Lactose Synthesis
	17. Citric Acid Cycle
		1 Overview of the Citric Acid Cycle
		2 Synthesis of Acetyl-Coenzyme A
			A. Pyruvate Dehydrogenase Is a Multienzyme Complex
			B. The Pyruvate Dehydrogenase Complex Catalyzes Five Reactions
		3 Enzymes of the Citric Acid Cycle
			A. Citrate Synthase Joins an Acetyl Group to Oxaloacetate
			B. Aconitase Interconverts Citrate and Isocitrate
			C. NAD+-Dependent Isocitrate Dehydrogenase Releases CO2
			D. α-Ketoglutarate Dehydrogenase Resembles Pyruvate Dehydrogenase
			E. Succinyl-CoA Synthetase Produces GTP
			F. Succinate Dehydrogenase Generates FADH2
			G. Fumarase Produces Malate
			H. Malate Dehydrogenase Regenerates Oxaloacetate
		4 Regulation of the Citric Acid Cycle
			A. Pyruvate Dehydrogenase Is Regulated by Product Inhibition and Covalent Modification
			B. Three Enzymes Control the Rate of the Citric Acid Cycle
		5 Reactions Related to the Citric Acid Cycle
			A. Other Pathways Use Citric Acid Cycle Intermediates
			B. Some Reactions Replenish Citric Acid Cycle Intermediates
			C. The Glyoxylate Cycle Shares Some Steps with the Citric Acid Cycle
		Summary & Problems
		BOX 17-1 Pathways of Discovery Hans Krebs and the Citric Acid Cycle
		BOX 17-2 Biochemistry in Health and Disease Arsenic Poisoning
		BOX 17-3 Perspectives in Biochemistry Evolution of the Citric Acid Cycle
	18. Electron Transport and Oxidative Phosphorylation
		1 The Mitochondrion
			A. Mitochondria Contain a Highly Folded Inner Membrane
			B. Ions and Metabolites Enter Mitochondria via Transporters
		2 Electron Transport
			A. Electron Transport Is an Exergonic Process
			B. Electron Carriers Operate in Sequence
			C. Complex I Accepts Electrons from NADH
			D. Complex II Contributes Electrons to Coenzyme Q
			E. Complex III Translocates Protons via the Q Cycle
			F. Complex IV Reduces Oxygen to Water
		3 Oxidative Phosphorylation
			A. The Chemiosmotic Theory Links Electron Transport to ATP Synthesis
			B. ATP Synthase Is Driven by the Flow of Protons
			C. The P/O Ratio Relates the Amount of ATP Synthesized to the Amount of Oxygen Reduced
			D. Oxidative Phosphorylation Can Be Uncoupled from Electron Transport
		4 Control of Oxidative Metabolism
			A. The Rate of Oxidative Phosphorylation Depends on the ATP and NADH Concentrations
			B. Aerobic Metabolism Has Some Disadvantages
		Summary & Problems
		BOX 18-1 Perspectives in Biochemistry Cytochromes Are Electron-Transport Heme Proteins
		BOX 18-2 Pathways of Discovery Peter Mitchell and the Chemiosmotic Theory
		BOX 18-3 Perspectives in Biochemistry Bacterial Electron Transport and Oxidative Phosphorylation
		BOX 18-4 Perspectives in Biochemistry Uncoupling in Brown Adipose Tissue Generates Heat
		BOX 18-5 Biochemistry in Health and Disease Oxygen Deprivation in Heart Attack and Stroke
	19. Photosynthesis
		1 Chloroplasts
			A. The Light Reactions Take Place in the Thylakoid Membrane
			B. Pigment Molecules Absorb Light
		2 The Light Reactions
			A. Light Energy Is Transformed to Chemical Energy
			B. Electron Transport in Photosynthetic Bacteria Follows a Circular Path
			C. Two-Center Electron Transport Is a Linear Pathway That Produces O2 and NADPH
			D. The Proton Gradient Drives ATP Synthesis by Photophosphorylation
		3 The Dark Reactions
			A. The Calvin Cycle Fixes CO2
			B. Calvin Cycle Products Are Converted to Starch, Sucrose, and Cellulose
			C. The Calvin Cycle Is Controlled Indirectly by Light
			D. Photorespiration Competes with Photosynthesis
		Summary & Problems
		BOX 19-1 Perspectives in Biochemistry Segregation of PSI and PSII
	20. Lipid Metabolism
		1 Lipid Digestion, Absorption, and Transport
			A. Triacylglycerols Are Digested before They Are Absorbed
			B. Lipids Are Transported as Lipoproteins
		2 Fatty Acid Oxidation
			A. Fatty Acids Are Activated by Their Attachment to Coenzyme A
			B. Carnitine Carries Acyl Groups across the Mitochondrial Membrane
			C. β Oxidation Degrades Fatty Acids to Acetyl-CoA
			D. Oxidation of Unsaturated Fatty Acids Requires Additional Enzymes
			E. Oxidation of Odd-Chain Fatty Acids Yields Propionyl-CoA
			F. Peroxisomal β Oxidation Differs from Mitochondrial β Oxidation
		3 Ketone Bodies
		4 Fatty Acid Biosynthesis
			A. Mitochondrial Acetyl-CoA Must Be Transported into the Cytosol
			B. Acetyl-CoA Carboxylase Produces Malonyl-CoA
			C. Fatty Acid Synthase Catalyzes Seven Reactions
			D. Fatty Acids May Be Elongated and Desaturated
			E. Fatty Acids Are Esterified to Form Triacylglycerols
		5 Regulation of Fatty Acid Metabolism
		6 Synthesis of Other Lipids
			A. Glycerophospholipids Are Built from Intermediates of Triacylglycerol Synthesis
			B. Sphingolipids Are Built from Palmitoyl-CoA and Serine
			C. C20 Fatty Acids Are the Precursors of Prostaglandins
		7 Cholesterol Metabolism
			A. Cholesterol Is Synthesized from Acetyl-CoA
			B. HMG-CoA Reductase Controls the Rate of Cholesterol Synthesis
			C. Abnormal Cholesterol Transport Leads to Atherosclerosis
		Summary & Problems
		BOX 20-1 Biochemistry in Health and Disease Vitamin B12 Deficiency
		BOX 20-2 Pathways of Discovery Dorothy Crowfoot Hodgkin and the Structure of Vitamin B12
		BOX 20-3 Perspectives in Biochemistry Polyketide Synthesis
		BOX 20-4 Biochemistry in Health and Disease Sphingolipid Degradation and Lipid Storage Diseases
	21. Amino Acid Metabolism
		1 Protein Degradation
			A. Lysosomes Degrade Many Proteins
			B. Ubiquitin Marks Proteins for Degradation
			C. The Proteasome Unfolds and Hydrolyzes Ubiquitinated Polypeptides
		2 Amino Acid Deamination
			A. Transaminases Use PLP to Transfer Amino Groups
			B. Glutamate Can Be Oxidatively Deaminated
		3 The Urea Cycle
			A. Five Enzymes Carry Out the Urea Cycle
			B. The Urea Cycle Is Regulated by Substrate Availability
		4 Breakdown of Amino Acids
			A. Alanine, Cysteine, Glycine, Serine, and Threonine Are Degraded to Pyruvate
			B. Asparagine and Aspartate Are Degraded to Oxaloacetate
			C. Arginine, Glutamate, Glutamine, Histidine, and Proline Are Degraded to α-Ketoglutarate
			D. Methionine, Threonine, Isoleucine, and Valine Are Degraded to Succinyl-CoA
			E. Leucine and Lysine Are Degraded Only to Acetyl-CoA and/or Acetoacetate
			F. Tryptophan Is Degraded to Alanine and Acetoacetate
			G. Phenylalanine and Tyrosine Are Degraded to Fumarate and Acetoacetate
		5 Amino Acid Biosynthesis
			A. Nonessential Amino Acids Are Synthesized from Common Metabolites
			B. Plants and Microorganisms Synthesize the Essential Amino Acids
		6 Other Products of Amino Acid Metabolism
			A. Heme Is Synthesized from Glycine and Succinyl-CoA
			B. Amino Acids Are Precursors of Physiologically Active Amines
			C. Nitric Oxide Is Derived from Arginine
		7 Nitrogen Fixation
			A. Nitrogenase Reduces N2 to NH3
			B. Fixed Nitrogen Is Assimilated into Biological Molecules
		Summary & Problems
		BOX 21-1 Biochemistry in Health and Disease Homocysteine, a Marker of Disease
		BOX 21-2 Biochemistry in Health and Disease Phenylketonuria and Alcaptonuria Result from Defects in Phenylalanine Degradation
		BOX 21-3 Biochemistry in Health and Disease The Porphyrias
	22. Mammalian Fuel Metabolism: Integration and Regulation
		1 Organ Specialization
			A. The Brain Requires a Steady Supply of Glucose
			B. Muscle Utilizes Glucose, Fatty Acids, and Ketone Bodies
			C. Adipose Tissue Stores and Releases Fatty Acids and Hormones
			D. Liver Is the Body’s Central Metabolic Clearinghouse
			E. Kidney Filters Wastes and Maintains Blood pH
			F. Blood Transports Metabolites in Interorgan Metabolic Pathways
		2 Hormonal Control of Fuel Metabolism
			A. Insulin Release Is Triggered by Glucose
			B. Glucagon and Catecholamines Counter the Effects of Insulin
		3 Metabolic Homeostasis: The Regulation of Energy Metabolism, Appetite, and Body Weight
			A. AMP-Dependent Protein Kinase Is the Cell’s Fuel Gauge
			B. Adipocytes and Other Tissues Help Regulate Fuel Metabolism and Appetite
			C. Energy Expenditure Can Be Controlled by Adaptive Thermogenesis
		4 Disturbances in Fuel Metabolism
			A. Starvation Leads to Metabolic Adjustments
			B. Diabetes Mellitus Is Characterized by High Blood Glucose Levels
			C. Obesity Is Usually Caused by Excessive Food Intake
			D. Cancer Metabolism
		Summary & Problems
		BOX 22-1 Biochemistry in Health and Disease The Intestinal Microbiome
		BOX 22-2 Pathways of Discovery Frederick Banting and Charles Best and the Discovery of Insulin
PART V - GENE EXPRESSION AND REPLICATION [23-28]
	23. Nucleotide Metabolism
		1 Synthesis of Purine Ribonucleotides
			A. Purine Synthesis Yields Inosine Monophosphate
			B. IMP Is Converted to Adenine and Guanine Ribonucleotides
			C. Purine Nucleotide Biosynthesis Is Regulated at Several Steps
			D. Purines Can Be Salvaged
		2 Synthesis of Pyrimidine Ribonucleotides
			A. UMP Is Synthesized in Six Steps
			B. UMP Is Converted to UTP and CTP
			C. Pyrimidine Nucleotide Biosynthesis Is Regulated at ATCase or Carbamoyl Phosphate Synthetase II
		3 Formation of Deoxyribonucleotides
			A. Ribonucleotide Reductase Converts Ribonucleotides to Deoxyribonucleotides
			B. dUMP Is Methylated to Form Thymine
		4 Nucleotide Degradation
			A. Purine Catabolism Yields Uric Acid
			B. Some Animals Degrade Uric Acid
			C. Pyrimidines Are Broken Down to Malonyl-CoA and Methylmalonyl-CoA
		Summary & Problems
		BOX 23-1 Biochemistry in Health and Disease Inhibition of Thymidylate Synthesis in Cancer Therapy
		BOX 23-2 Pathways of Discovery Gertrude Elion and Purine Derivatives
	24. Nucleic Acid Structure
		1 The DNA Helix
			A. DNA Can Adopt Different Conformations
			B. DNA Has Limited Flexibility
			C. DNA Can Be Supercoiled
			D. Topoisomerases Alter DNA Supercoiling
		2 Forces Stabilizing Nucleic Acid Structures
			A. Nucleic Acids Are Stabilized by Base Pairing, Stacking, and Ionic Interactions
			B. DNA Can Undergo Denaturation and Renaturation
			C. RNA Structures Are Highly Variable
		3 Fractionation of Nucleic Acids
			A. Nucleic Acids Can Be Purified by Chromatography
			B. Electrophoresis Separates Nucleic Acids by Size
		4 DNA–Protein Interactions
			A. Restriction Endonucleases Distort DNA on Binding
			B. Prokaryotic Repressors Often Include a DNA-Binding Helix
			C. Eukaryotic Transcription Factors May Include Zinc Fingers or Leucine Zippers
		5 Eukaryotic Chromosome Structure
			A. DNA Coils around Histones to Form Nucleosomes
			B. Chromatin Forms Higher-Order Structures
		Summary & Problems
		BOX 24-1 Pathways of Discovery Rosalind Franklin and the Structure of DNA
		BOX 24-2 Biochemistry in Health and Disease Inhibitors of Topoisomerases as Antibiotics and Anticancer Chemotherapeutic Agents
		BOX 24-3 Perspectives in Biochemistry The RNA World
	25. DNA Replication, Repair, and Recombination
		1 Overview of DNA Replication
		2 Prokaryotic DNA Replication
			A. DNA Polymerases Add the Correctly Paired Nucleotides
			B. Replication Initiation Requires Helicase and Primase
			C. The Leading and Lagging Strands Are Synthesized Simultaneously
			D. Replication Terminates at Specific Sites
			E. DNA Is Replicated with High Fidelity
		3 Eukaryotic DNA Replication
			A. Eukaryotes Use Several DNA Polymerases
			B. Eukaryotic DNA Is Replicated from Multiple Origins
			C. Telomerase Extends Chromosome Ends
		4 DNA Damage
			A. Environmental and Chemical Agents Generate Mutations
			B. Many Mutagens Are Carcinogens
		5 DNA Repair
			A. Some Damage Can Be Directly Reversed
			B. Base Excision Repair Requires a Glycosylase
			C. Nucleotide Excision Repair Removes a Segment of a DNA Strand
			D. Mismatch Repair Corrects Replication Errors
			E. Some DNA Repair Mechanisms Introduce Errors
		6 Recombination
			A. Homologous Recombination Involves Several Protein Complexes
			B. DNA Can Be Repaired by Recombination
			C. CRISPR–Cas9, a System for Editing and Regulating Genomes
			D. Transposition Rearranges Segments of DNA
		Summary & Problems
		BOX 25-1 Pathways of Discovery Arthur Kornberg and DNA Polymerase I
		BOX 25-2 Perspectives in Biochemistry Reverse Transcriptase
		BOX 25-3 Biochemistry in Health and Disease Telomerase, Aging, and Cancer
		BOX 25-4 Perspectives in Biochemistry DNA Methylation
		BOX 25-5 Perspectives in Biochemistry Why Doesn’t DNA Contain Uracil?
	26. Transcription and RNA Processing
		1 Prokaryotic RNA Transcription
			A. RNA Polymerase Resembles Other Polymerases
			B. Transcription Is Initiated at a Promoter
			C. The RNA Chain Grows from the 5\' to 3\' End
			D. Transcription Terminates at Specific Sites
		2 Transcription in Eukaryotes
			A. Eukaryotes Have Several RNA Polymerases
			B. Each Polymerase Recognizes a Different Type of Promoter
			C. Transcription Factors Are Required to Initiate Transcription
		3 Posttranscriptional Processing
			A. Messenger RNAs Undergo 5\' Capping and Addition of a 3\' Tail
			B. Splicing Removes Introns from Eukaryotic Genes
			C. Ribosomal RNA Precursors May Be Cleaved, Modified, and Spliced
			D. Transfer RNAs Are Processed by Nucleotide Removal, Addition, and Modification
			Summary & Problems
		BOX 26-1 Perspectives in Biochemistry Collisions between DNA Polymerase and RNA Polymerase
		BOX 26-2 Biochemistry in Health and Disease Inhibitors of Transcription
		BOX 26-3 Pathways of Discovery Richard Roberts and Phillip Sharp and the Discovery of Introns
	27. Protein Synthesis
		1 The Genetic Code
			A. Codons Are Triplets That Are Read Sequentially
			B. The Genetic Code Was Systematically Deciphered
			C. The Genetic Code Is Degenerate and Nonrandom
		2 Transfer RNA and Its Aminoacylation
			A. All tRNAs Have Similar Structures
			B. Aminoacyl–tRNA Synthetases Attach Amino Acids to tRNAs
			C. Most tRNAs Recognize More than One Codon
		3 Ribosomes
			A. The Prokaryotic Ribosome Consists of Two Subunits
			B. The Eukaryotic Ribosome Contains a Buried Prokaryotic Ribosome
		4 Translation
			A. Chain Initiation Requires an Initiator tRNA and Initiation Factors
			B. The Ribosome Decodes the mRNA, Catalyzes Peptide Bond Formation, Then Moves to the Next Codon
			C. Release Factors Terminate Translation
		5 Posttranslational Processing
			A. Ribosome-Associated Chaperones Help Proteins Fold
			B. Newly Synthesized Proteins May Be Covalently Modified
		Summary & Problems
		BOX 27-1 Perspectives in Biochemistry Evolution of the Genetic Code
		BOX 27-2 Perspectives in Biochemistry Expanding the Genetic Code
		BOX 27-3 Biochemistry in Health and Disease The Effects of Antibiotics on Protein Synthesis
	28. Regulation of Gene Expression
		1 Genome Organization
			A. Gene Number Varies among Organisms
			B. Some Genes Occur in Clusters
			C. Eukaryotic Genomes Contain Repetitive DNA Sequences
		2 Regulation of Prokaryotic Gene Expression
			A. The lac Operon Is Controlled by a Repressor
			B. Catabolite-Repressed Operons Can Be Activated
			C. Attenuation Regulates Transcription Termination
			D. Riboswitches Are Metabolite-Sensing RNAs
		3 Regulation of Eukaryotic Gene Expression
			A. Chromatin Structure Influences Gene Expression
			B. Eukaryotes Contain Multiple Transcriptional Activators
			C. Posttranscriptional Control Mechanisms
			D. Antibody Diversity Results from Somatic Recombination and Hypermutation
		4 The Cell Cycle, Cancer, Apoptosis, and Development
			A. Progress through the Cell Cycle Is Tightly Regulated
			B. Tumor Suppressors Prevent Cancer
			C. Apoptosis Is an Orderly Process
			D. Development Has a Molecular Basis
		Summary & Problems
		BOX 28-1 Biochemistry in Health and Disease Trinucleotide Repeat Diseases
		BOX 28-2 Perspectives in Biochemistry X Chromosome Inactivation
		BOX 28-3 Perspectives in Biochemistry Nonsense-Mediated Decay
SOLUTIONS to Odd-Numbered Problems
	01
	02
	03
	04
	05
	06
	07
	08
	09
	10
	11
	12
	13
	14
	15
	16
	17
	18
	19
	20
	21
	22
	23
	24
	25
	26
	27
	28
Glossary
	A
	B
	C
	D
	E
	F - G
	H
	I
	J - K
	L
	M
	N
	O - P
	Q - R
	S
	T
	U
	V
	W
	X - Y - Z
INDEX
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J - K
	L
	M
	N
	O
	P
	Q - R
	S
	T
	U
	V - W - X
	Y - Z
Applications Index
Some Common Biochemical Abbreviations
Amino Acids
Thermodynamic Constants and Conversion Factors
Standard Genetic Code
Copyright
Title Page
Dedication
Contents
Chapter 1: ‘I’m thinking’ – Oh, but are you?
Chapter 2: Renegade perception
Chapter 3: The Pushbacker sting
Chapter 4: ‘Covid’: The calculated catastrophe
Chapter 5: There is no ‘virus’
Chapter 6: Sequence of deceit
Chapter 7: War on your mind
Chapter 8: ‘Reframing’ insanity
Chapter 9: We must have it? So what is it?
Chapter 10: Human 2.0
Chapter 11: Who controls the Cult?
Chapter 12: Escaping Wetiko
Postscript
Appendix: Cowan-Kaufman-Morell Statement on Virus Isolation
Bibliography
Index