Biochemistry

Cover
Title Page
Copyright Page
Dedication
About the Authors
Preface
Acknowledgments
Brief Contents
Contents
Part I THE MOLECULAR DESIGN OF LIFE
	CHAPTER 1 Biochemistry: An Evolving Science
		1.1 Biochemical Unity Underlies Biological Diversity
		1.2 DNA Illustrates the Interplay Between Form and Function
			DNA is constructed from four building blocks
			Two single strands of DNA combine to form a double helix
			DNA structure explains heredity and the storage of information
		1.3 Concepts from Chemistry Explain the Properties of Biological Molecules
			The formation of the DNA double helix as a key example
			The double helix can form from its component strands
			Covalent and noncovalent bonds are important for the structure and stability of biological molecules
			The double helix is an expression of the rules of chemistry
			The laws of thermodynamics govern the behavior of biochemical systems
			Heat is released in the formation of the double helix
			Acid–base reactions are central in many biochemical processes
			Acid–base reactions can disrupt the double helix
			Buffers regulate pH in organisms and in the laboratory
		1.4 The Genomic Revolution Is Transforming Biochemistry, Medicine, and Other Fields
			Genome sequencing has transformed biochemistry and other fields
			Environmental factors influence human biochemistry
			Genome sequences encode proteins and patterns of expression
		APPENDIX: Visualizing Molecular Structures I: Small Molecules
	CHAPTER 2 Protein Composition and Structure
		2.1 Proteins Are Built from a Repertoire of 20 Amino Acids
		2.2 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains
			Proteins have unique amino acid sequences specified by genes
			Polypeptide chains are flexible yet conformationally restricted
		2.3 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops
			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
		2.4 Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores
		2.5 Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures
		2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure
			Amino acids have different propensities for forming α helices, β sheets, and turns
			Protein folding is a highly cooperative process
			Proteins fold by progressive stabilization of intermediates rather than by random search
			Prediction of three-dimensional structure from sequence remains a great challenge
			Some proteins are inherently unstructured and can exist in multiple conformations
			Protein misfolding and aggregation are associated with some neurological diseases
			Protein modification and cleavage confer new capabilities
		APPENDIX: Visualizing Molecular Structures II: Proteins
	CHAPTER 3 Exploring Proteins and Proteomes
		The proteome is the functional representation of the genome
		3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function
			The assay: How do we recognize the protein that we are looking for?
			Proteins must be released 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 protein purification scheme can be quantitatively evaluated
			Ultracentrifugation is valuable for separating biomolecules and determining their masses
			Protein purification can be made easier with the use of recombinant DNA technology
		3.2 Immunology Provides Important Techniques with Which to Investigate Proteins
			Antibodies to specific proteins can be generated
			Monoclonal antibodies with virtually any desired specificity can be readily prepared
			Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay
			Western blotting permits the detection of proteins separated by gel electrophoresis
			Fluorescent markers make the visualization of proteins in the cell possible
		3.3 Mass Spectrometry is a Powerful Technique for the Identification of Peptides and Proteins
			Peptides can be sequenced by mass spectrometry
			Proteins can be specifically cleaved into small peptides to facilitate analysis
			Genomic and proteomic methods are complementary
			The amino acid sequence of a protein provides valuable information
			Individual proteins can be identified by mass spectrometry
		3.4 Peptides Can Be Synthesized by Automated Solid-Phase Methods
		3.5 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography and NMR Spectroscopy
			X-ray crystallography reveals three-dimensional structure in atomic detail
			Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution
	CHAPTER 4 DNA, RNA, and the Flow of Genetic Information
		4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar–Phosphate Backbone
			RNA and DNA 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
		4.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure
			The double helix is stabilized by hydrogen bonds and van der Waals interactions
			DNA can assume a variety of structural forms
			Z-DNA is a left-handed double helix in which backbone phosphates zigzag
			Some DNA molecules are circular and supercoiled
			Single-stranded nucleic acids can adopt elaborate structures
		4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information
			Differences in DNA density established the validity of the semiconservative replication hypothesis
			The double helix can be reversibly melted
		4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates
			DNA polymerase catalyzes phosphodiester-bridge formation
			The genes of some viruses are made of RNA
		4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules
			Several kinds of RNA play key roles in gene expression
			All cellular RNA is synthesized by RNA polymerases
			RNA polymerases take instructions from DNA templates
			Transcription begins near promoter sites and ends at terminator sites
			Transfer RNAs are the adaptor molecules in protein synthesis
		4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point
			Major features of the genetic code
			Messenger RNA contains start and stop signals for protein synthesis
			The genetic code is nearly universal
		4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons
			RNA processing generates mature RNA
			Many exons encode protein domains
	CHAPTER 5 Exploring Genes and Genomes
		5.1 The Exploration of Genes Relies on Key Tools
			Restriction enzymes split DNA into specific fragments
			Restriction fragments can be separated by gel electrophoresis and visualized
			DNA can be sequenced by controlled termination of replication
			DNA probes and genes can be synthesized by automated solid-phase methods
			Selected DNA sequences can be greatly amplified by the polymerase chain reaction
			PCR is a powerful technique in medical diagnostics, forensics, and studies of molecular evolution
			The tools for recombinant DNA technology have been used to identify disease-causing mutations
		5.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology
			Restriction enzymes and DNA ligase are key tools in forming recombinant DNA molecules
			Plasmids and λ phage are choice vectors for DNA cloning in bacteria
			Bacterial and yeast artificial chromosomes
			Specific genes can be cloned from digests of genomic DNA
			Complementary DNA prepared from mRNA can be expressed in host cells
			Proteins with new functions can be created through directed changes in DNA
			Recombinant methods enable the exploration of the functional effects of disease-causing mutations
		5.3 Complete Genomes Have Been Sequenced and Analyzed
			The genomes of organisms ranging from bacteria to multicellular eukaryotes have been sequenced
			The sequence of the human genome has been completed
			Next-generation sequencing methods enable the rapid determination of a complete genome sequence
			Comparative genomics has become a powerful research tool
		5.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision
			Gene-expression levels can be comprehensively examined
			New genes inserted into eukaryotic cells can be efficiently expressed
			Transgenic animals harbor and express genes introduced into their germ lines
			Gene disruption and genome editing provide clues to gene function and opportunities for new therapies
			RNA interference provides an additional tool for disrupting gene expression
			Tumor-inducing plasmids can be used to introduce new genes into plant cells
			Human gene therapy holds great promise for medicine
	CHAPTER 6 Exploring Evolution and Bioinformatics
		6.1 Homologs Are Descended from a Common Ancestor
		6.2 Statistical Analysis of Sequence Alignments Can Detect Homology
			The statistical significance of alignments can be estimated by shuffling
			Distant evolutionary relationships can be detected through the use of substitution matrices
			Databases can be searched to identify homologous sequences
		6.3 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships
			Tertiary structure is more conserved than primary structure
			Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments
			Repeated motifs can be detected by aligning sequences with themselves
			Convergent evolution illustrates common solutions to biochemical challenges
			Comparison of RNA sequences can be a source of insight into RNA secondary structures
		6.4 Evolutionary Trees Can Be Constructed on the Basis of Sequence Information
			Horizontal gene transfer events may explain unexpected branches of the evolutionary tree
		6.5 Modern Techniques Make the Experimental Exploration of Evolution Possible
			Ancient DNA can sometimes be amplified and sequenced
			Molecular evolution can be examined experimentally
	CHAPTER 7 Hemoglobin: Portrait of a Protein in Action
		7.1 Myoglobin and Hemoglobin Bind Oxygen at Iron Atoms in Heme
			Changes in heme electronic structure upon oxygen binding are the basis for functional imaging studies
			The structure of myoglobin prevents the release of reactive oxygen species
			Human hemoglobin is an assembly of four myoglobin-like subunits
		7.2 Hemoglobin Binds Oxygen Cooperatively
			Oxygen binding markedly changes the quaternary structure of hemoglobin
			Hemoglobin cooperativity can be potentially explained by several models
			Structural changes at the heme groups are transmitted to the α1β1–α2β2 interface
			2,3-Bisphosphoglycerate in red cells is crucial in determining the oxygen affinity of hemoglobin
			Carbon monoxide can disrupt oxygen transport by hemoglobin
		7.3 Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen: The Bohr Effect
		7.4 Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease
			Sickle-cell anemia results from the aggregation of mutated deoxyhemoglobin molecules
			Thalassemia is caused by an imbalanced production of hemoglobin chains
			The accumulation of free alpha-hemoglobin chains is prevented
			Additional globins are encoded in the human genome
		APPENDIX: Binding Models Can Be Formulated in Quantitative Terms: The Hill Plot and the Concerted Model
	CHAPTER 8 Enzymes: Basic Concepts and Kinetics
		8.1 Enzymes Are Powerful and Highly Specific Catalysts
			Many enzymes require cofactors for activity
			Enzymes can transform energy from one form into another
		8.2 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 only the reaction rate and not the reaction equilibrium
		8.3 Enzymes Accelerate Reactions by Facilitating 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
		8.4 The Michaelis–Menten Model Accounts for the Kinetic Properties of Many Enzymes
			Kinetics is the study of reaction rates
			The steady-state assumption facilitates a description of enzyme kinetics
			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
			Allosteric enzymes do not obey Michaelis–Menten kinetics
		8.5 Enzymes Can Be Inhibited by Specific Molecules
			The different types of reversible inhibitors are kinetically distinguishable
			Irreversible inhibitors can be used to map the active site
			Penicillin irreversibly inactivates a key enzyme in bacterial cell-wall synthesis
			Transition-state analogs are potent inhibitors of enzymes
			Catalytic antibodies demonstrate the importance of selective binding of the transition state to enzymatic activity
		8.6 Enzymes Can Be Studied One Molecule at a Time
		APPENDIX: Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze
	CHAPTER 9 Catalytic Strategies
		A few basic catalytic principles are used by many enzymes
		9.1 Proteases Facilitate a Fundamentally Difficult Reaction
			Chymotrypsin possesses a highly reactive serine residue
			Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate
			Serine is part of a catalytic triad that also includes histidine and aspartate
			Catalytic triads are found in other hydrolytic enzymes
			The catalytic triad has been dissected by site-directed mutagenesis
			Cysteine, aspartyl, and metalloproteases are other major classes of peptide-cleaving enzymes
			Protease inhibitors are important drugs
		9.2 Carbonic Anhydrases Make a Fast Reaction Faster
			Carbonic anhydrase contains a bound zinc ion essential for catalytic activity
			Catalysis entails zinc activation of a water molecule
			A proton shuttle facilitates rapid regeneration of the active form of the enzyme
		9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions
			Cleavage is by in-line displacement of 3\'-oxygen from phosphorus by magnesium-activated water
			Restriction enzymes require magnesium for catalytic activity
			The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules, ensuring specificity
			Host-cell DNA is protected by the addition of methyl groups to specific bases
			Type II restriction enzymes have a catalytic core in common and are probably related by horizontal gene transfer
		9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work
			ATP hydrolysis proceeds by the attack of water on the gamma-phosphoryl group
			Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change
			The altered conformation of myosin persists for a substantial period of time
			Scientists can watch single molecules of myosin move
			Myosins are a family of enzymes containing P-loop structures
	CHAPTER 10 Regulatory Strategies
		10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway
			Allosterically regulated enzymes do not follow Michaelis–Menten kinetics
			ATCase consists of separable catalytic and regulatory subunits
			Allosteric interactions in ATCase are mediated by large changes in quaternary structure
			Allosteric regulators modulate the T-to-R equilibrium
		10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages
		10.3 Covalent Modification Is a Means of Regulating Enzyme Activity
			Kinases and phosphatases control the extent of protein phosphorylation
			Phosphorylation is a highly effective means of regulating the activities of target proteins
			Cyclic AMP activates protein kinase A by altering the quaternary structure
			ATP and the target protein bind to a deep cleft in the catalytic subunit of protein kinase A
		10.4 Many Enzymes Are Activated by Specific Proteolytic Cleavage
			Chymotrypsinogen is activated by specific cleavage of a single peptide bond
			Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site
			The generation of trypsin from trypsinogen leads to the activation of other zymogens
			Some proteolytic enzymes have specific inhibitors
			Blood clotting is accomplished by a cascade of zymogen activations
			Prothrombin requires a vitamin K-dependent modification for activation
			Fibrinogen is converted by thrombin into a fibrin clot
			Vitamin K is required for the formation of γ-carboxyglutamate
			The clotting process must be precisely regulated
			Hemophilia revealed an early step in clotting
	CHAPTER 11 Carbohydrates
		11.1 Monosaccharides Are the Simplest Carbohydrates
			Many common sugars exist in cyclic forms
			Pyranose and furanose rings can assume different conformations
			Glucose is a reducing sugar
			Monosaccharides are joined to alcohols and amines through glycosidic bonds
			Phosphorylated sugars are key intermediates in energy generation and biosyntheses
		11.2 Monosaccharides Are Linked to Form Complex Carbohydrates
			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
		11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins
			Carbohydrates can be linked to proteins through asparagine (N-linked) or through serine or threonine (O-linked) residues
			The glycoprotein erythropoietin is a vital hormone
			Glycosylation functions in nutrient sensing
			Proteoglycans, composed of polysaccharides and protein, have important structural roles
			Proteoglycans are important components of cartilage
			Mucins are glycoprotein components of mucus
			Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex
			Specific enzymes are responsible for oligosaccharide assembly
			Blood groups are based on protein glycosylation patterns
			Errors in glycosylation can result in pathological conditions
			Oligosaccharides can be “sequenced”
		11.4 Lectins Are Specific Carbohydrate-Binding Proteins
			Lectins promote interactions between cells
			Lectins are organized into different classes
			Influenza virus binds to sialic acid residues
	CHAPTER 12 Lipids and Cell Membranes
		Many common features underlie the diversity of biological membranes
		12.1 Fatty Acids Are Key Constituents of Lipids
			Fatty acid names are based on their parent hydrocarbons
			Fatty acids vary in chain length and degree of unsaturation
		12.2 There Are Three Common Types of Membrane Lipids
			Phospholipids are the major class of membrane lipids
			Membrane lipids can include carbohydrate moieties
			Cholesterol is a lipid based on a steroid nucleus
			Archaeal membranes are built from ether lipids with branched chains
			A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety
		12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media
			Lipid vesicles can be formed from phospholipids
			Lipid bilayers are highly impermeable to ions and most polar molecules
		12.4 Proteins Carry Out Most Membrane Processes
			Proteins associate with the lipid bilayer in a variety of ways
			Proteins interact with membranes in a variety of ways
			Some proteins associate with membranes through covalently attached hydrophobic groups
			Transmembrane helices can be accurately predicted from amino acid sequences
		12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane
			The fluid mosaic model allows lateral movement but not rotation through the membrane
			Membrane fluidity is controlled by fatty acid composition and cholesterol content
			Lipid rafts are highly dynamic complexes formed between cholesterol and specific lipids
			All biological membranes are asymmetric
		12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes
	CHAPTER 13 Membrane Channels and Pumps
		The expression of transporters largely defines the metabolic activities of a given cell type
		13.1 The Transport of Molecules Across a Membrane May Be Active or Passive
			Many molecules require protein transporters to cross membranes
			Free energy stored in concentration gradients can be quantified
		13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes
			P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes
			Digitalis specifically inhibits the Na+–K+ pump by blocking its dephosphorylation
			P-type ATPases are evolutionarily conserved and play a wide range of roles
			Multidrug resistance highlights a family of membrane pumps with ATP-binding cassette domains
		13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another
		13.4 Specific Channels Can Rapidly Transport Ions Across Membranes
			Action potentials are mediated by transient changes in Na+ and K+ permeability
			Patch-clamp conductance measurements reveal the activities of single channels
			The structure of a potassium ion channel is an archetype for many ion-channel structures
			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
			Voltage gating requires substantial conformational changes in specific ion-channel domains
			A channel can be inactivated by occlusion of the pore: the ball-and-chain model
			The acetylcholine receptor is an archetype for ligand-gated ion channels
			Action potentials integrate the activities of several ion channels working in concert
			Disruption of ion channels by mutations or chemicals can be potentially life-threatening
		13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells
		13.6 Specific Channels Increase the Permeability of Some Membranes to Water
	CHAPTER 14 Signal-Transduction Pathways
		Signal transduction depends on molecular circuits
		14.1 Heterotrimeric G Proteins Transmit Signals and Reset Themselves
			Ligand binding to 7TM receptors leads to the activation of heterotrimeric 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
			G proteins spontaneously reset themselves through GTP hydrolysis
			Some 7TM receptors activate the phosphoinositide cascade
			Calcium ion is a widely used second messenger
			Calcium ion often activates the regulatory protein calmodulin
		14.2 Insulin Signaling: Phosphorylation Cascades Are Central to Many Signal-Transduction Processes
			The insulin receptor is a dimer that closes around a bound insulin molecule
			Insulin binding results in the cross-phosphorylation and activation of the insulin receptor
			The activated insulin-receptor kinase initiates a kinase cascade
			Insulin signaling is terminated by the action of phosphatases
		14.3 EGF Signaling: Signal-Transduction Pathways Are Poised to Respond
			EGF binding results in the dimerization of the EGF receptor
			The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail
			EGF signaling leads to the activation of Ras, a small G protein
			Activated Ras initiates a protein kinase cascade
			EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras
		14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways
		14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases
			Monoclonal antibodies can be used to inhibit signal-transduction pathways activated in tumors
			Protein kinase inhibitors can be effective anticancer drugs
			Cholera and whooping cough are the result of altered G-protein activity
Part II TRANSDUCING AND STORING ENERGY
	CHAPTER 15 Metabolism: Basic Concepts and Design
		15.1 Metabolism Is Composed of Many Coupled, Interconnecting Reactions
			Metabolism consists of energy-yielding and energy-requiring reactions
			A thermodynamically unfavorable reaction can be driven by a favorable reaction
		15.2 ATP Is the Universal Currency of Free Energy in Biological Systems
			ATP hydrolysis is exergonic
			ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions
			The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products
			Phosphoryl-transfer potential is an important form of cellular energy transformation
		15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
			Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis
			Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis
			Phosphates play a prominent role in biochemical processes
			Energy from foodstuffs is extracted in three stages
		15.4 Metabolic Pathways Contain Many Recurring Motifs
			Activated carriers exemplify the modular design and economy of metabolism
			Many activated carriers are derived from vitamins
			Key reactions are reiterated throughout metabolism
			Metabolic processes are regulated in three principal ways
			Aspects of metabolism may have evolved from an RNA world
	CHAPTER 16 Glycolysis and Gluconeogenesis
		Glucose is generated from dietary carbohydrates
		Glucose is an important fuel for most organisms
		16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms
			Hexokinase traps glucose in the cell and begins glycolysis
			Fructose 1,6-bisphosphate is generated from glucose 6-phosphate
			The six-carbon sugar is cleaved into two three-carbon fragments
			Mechanism: Triose phosphate isomerase salvages a three-carbon fragment
			The oxidation of an aldehyde to an acid powers the formation of a compound with high phosphoryl-transfer potential
			Mechanism: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate
			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
			NAD+ is regenerated from the metabolism of pyruvate
			Fermentations provide usable energy in the absence of oxygen
			The binding site for NAD+ is similar in many dehydrogenases
			Fructose is converted into glycolytic intermediates by fructokinase
			Excessive fructose consumption can lead to pathological conditions
			Galactose is converted into glucose 6-phosphate
			Many adults are intolerant of milk because they are deficient in lactase
			Galactose is highly toxic if the transferase is missing
		16.2 The Glycolytic Pathway Is Tightly Controlled
			Glycolysis in muscle is regulated to meet the need for ATP
			The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver
			A family of transporters enables glucose to enter and leave animal cells
			Aerobic glycolysis is a property of rapidly growing cells
			Cancer and endurance training affect glycolysis in a similar fashion
		16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors
			Gluconeogenesis is not a 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
		16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated
			Energy charge determines whether glycolysis or gluconeogenesis will be most active
			The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration
			Substrate cycles amplify metabolic signals and produce heat
			Lactate and alanine formed by contracting muscle are used by other organs
			Glycolysis and gluconeogenesis are evolutionarily intertwined
	CHAPTER 17 The Citric Acid Cycle
		The citric acid cycle harvests high-energy electrons
		17.1 The Pyruvate Dehydrogenase Complex Links Glycolysis to the Citric Acid Cycle
			Mechanism: The synthesis of acetyl coenzyme A from pyruvate requires three enzymes and five coenzymes
			Flexible linkages allow lipoamide to move between different active sites
		17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units
			Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A
			Mechanism: 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
			A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A
			Mechanism: 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, ATP, and CO2
		17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled
			The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation
			The citric acid cycle is controlled at several points
			Defects in the citric acid cycle contribute to the development of cancer
		17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors
			The citric acid cycle must be capable of being rapidly replenished
			The disruption of pyruvate metabolism is the cause of beriberi and poisoning by mercury and arsenic
			The citric acid cycle may have evolved from preexisting pathways
		17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate
	CHAPTER 18 Oxidative Phosphorylation
		18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria
			Mitochondria are bounded by a double membrane
			Mitochondria are the result of an endosymbiotic event
		18.2 Oxidative Phosphorylation Depends on Electron Transfer
			The electron-transfer potential of an electron is measured as redox potential
			A 1.14-volt potential difference between NADH and molecular oxygen drives electron transport through the chain and favors the formation of a proton gradient
		18.3 The Respiratory Chain Consists of Four Complexes: Three Proton Pumps and a Physical Link to the Citric Acid Cycle
			Iron–sulfur clusters are common components of the electron transport chain
			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
			Toxic derivatives of molecular oxygen such as superoxide radicals are scavenged by protective enzymes
			Electrons can be transferred between groups that are not in contact
			The conformation of cytochrome c has remained essentially constant for more than a billion years
		18.4 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: The binding-change mechanism
			Rotational catalysis is the world’s smallest molecular motor
			Proton flow around the c ring powers ATP synthesis
			ATP synthase and G proteins have several common features
		18.5 Many 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 by ATP-ADP translocase
			Mitochondrial transporters for metabolites have a common tripartite structure
		18.6 The Regulation of Cellular Respiration Is Governed Primarily 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
			ATP synthase can be regulated
			Regulated uncoupling leads to the generation of heat
			Oxidative phosphorylation can be inhibited at many stages
			Mitochondrial diseases are being discovered
			Mitochondria play a key role in apoptosis
			Power transmission by proton gradients is a central motif of bioenergetics
	CHAPTER 19 The Light Reactions of Photosynthesis
		Photosynthesis converts light energy into chemical energy
		19.1 Photosynthesis Takes Place in Chloroplasts
			The primary events of photosynthesis take place in thylakoid membranes
			Chloroplasts arose from an endosymbiotic event
		19.2 Light Absorption by Chlorophyll Induces Electron Transfer
			A special pair of chlorophylls initiate charge separation
			Cyclic electron flow reduces the cytochrome of the reaction center
		19.3 Two Photosystems Generate a Proton Gradient and NADPH in Oxygenic Photosynthesis
			Photosystem II transfers electrons from water to plastoquinone and generates a proton gradient
			Cytochrome bf links photosystem II to photosystem I
			Photosystem I uses light energy to generate reduced ferredoxin, a powerful reductant
			Ferredoxin–NADP+ reductase converts NADP+ into NADPH
		19.4 A Proton Gradient across the Thylakoid Membrane Drives ATP Synthesis
			The ATP synthase of chloroplasts closely resembles those of mitochondria and prokaryotes
			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
		19.5 Accessory Pigments Funnel Energy into Reaction Centers
			Resonance energy transfer allows energy to move from the site of initial absorbance to the reaction center
			The components of photosynthesis are highly organized
			Many herbicides inhibit the light reactions of photosynthesis
		19.6 The Ability to Convert Light into Chemical Energy Is Ancient
			Artificial photosynthetic systems may provide clean, renewable energy
	CHAPTER 20 The Calvin Cycle and the Pentose Phosphate Pathway
		20.1 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
			Rubisco activity depends on magnesium and carbamate
			Rubisco activase is essential for rubisco activity
			Rubisco also catalyzes a wasteful oxygenase reaction: Catalytic imperfection
			Hexose phosphates are made from phosphoglycerate, and ribulose 1,5-bisphosphate is regenerated
			Three ATP and two NADPH molecules are used to bring carbon dioxide to the level of a hexose
			Starch and sucrose are the major carbohydrate stores in plants
		20.2 The Activity of the Calvin Cycle Depends on Environmental Conditions
			Rubisco is activated by light-driven changes in proton and magnesium ion concentrations
			Thioredoxin plays a key role in regulating the Calvin cycle
			The C4 pathway of tropical plants accelerates photosynthesis by concentrating carbon dioxide
			Crassulacean acid metabolism permits growth in arid ecosystems
		20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes 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
			Mechanism: Transketolase and transaldolase stabilize carbanionic intermediates by different mechanisms
		20.4 The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis
			The rate of the pentose phosphate pathway is controlled by the level of NADP+
			The flow of glucose 6-phosphate depends on the need for NADPH, ribose 5-phosphate, and ATP
			The pentose phosphate pathway is required for rapid cell growth
			Through the looking-glass: The Calvin cycle and the pentose phosphate pathway are mirror images
		20.5 Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species
			Glucose 6-phosphate dehydrogenase deficiency causes a drug-induced hemolytic anemia
			A deficiency of glucose 6-phosphate dehydrogenase confers an evolutionary advantage in some circumstances
	CHAPTER 21 Glycogen Metabolism
		Glycogen metabolism is the regulated release and storage of glucose
		21.1 Glycogen Breakdown Requires the Interplay of Several Enzymes
			Phosphorylase catalyzes the phosphorolytic cleavage of glycogen to release glucose 1-phosphate
			Mechanism: Pyridoxal phosphate participates in the phosphorolytic cleavage of glycogen
			A debranching enzyme also is needed for the breakdown of glycogen
			Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate
			The liver contains glucose 6-phosphatase, a hydrolytic enzyme absent from muscle
		21.2 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
		21.3 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
			The regulation of glycogen phosphorylase became more sophisticated as the enzyme evolved
		21.4 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 α-1,6 linkages
			Glycogen synthase is the key regulatory enzyme in glycogen synthesis
			Glycogen is an efficient storage form of glucose
		21.5 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 level
			A biochemical understanding of glycogen-storage diseases is possible
	CHAPTER 22 Fatty Acid Metabolism
		Fatty acid degradation and synthesis mirror each other in their chemical reactions
		22.1 Triacylglycerols Are Highly Concentrated Energy Stores
			Dietary lipids are digested by pancreatic lipases
			Dietary lipids are transported in chylomicrons
		22.2 The Use of Fatty Acids as Fuel Requires Three Stages of Processing
			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
			Carnitine carries long-chain activated fatty acids into the mitochondrial matrix
			Acetyl CoA, NADH, and FADH2 are generated in each round of fatty acid oxidation
			The complete oxidation of palmitate yields 106 molecules of ATP
		22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation
			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
			Vitamin B12 contains a corrin ring and a cobalt atom
			Mechanism: Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA
			Fatty acids are also oxidized in peroxisomes
			Ketone bodies are formed from acetyl CoA when fat breakdown predominates
			Ketone bodies are a major fuel in some tissues
			Animals cannot convert fatty acids into glucose
			Some fatty acids may contribute to the development of pathological conditions
		22.4 Fatty Acids Are Synthesized by Fatty Acid Synthase
			Fatty acids are synthesized and degraded by different pathways
			The formation of malonyl CoA is the committed step in fatty acid synthesis
			Intermediates in fatty acid synthesis are attached to an acyl carrier protein
			Fatty acid synthesis consists of a series of condensation, reduction, dehydration, and reduction reactions
			Fatty acids are synthesized by a multifunctional enzyme complex in animals
			The synthesis of palmitate requires 8 molecules of acetyl CoA, 14 molecules of NADPH, and 7 molecules of ATP
			Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis
			Several sources supply NADPH for fatty acid synthesis
			Fatty acid metabolism is altered in tumor cells
		22.5 The Elongation and Unsaturation of Fatty Acids are Accomplished by Accessory Enzyme Systems
			Membrane-bound enzymes generate unsaturated fatty acids
			Eicosanoid hormones are derived from polyunsaturated fatty acids
			Variations on a theme: Polyketide and nonribosomal peptide synthetases resemble fatty acid synthase
		22.6 Acetyl CoA Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism
			Acetyl CoA carboxylase is regulated by conditions in the cell
			Acetyl CoA carboxylase is regulated by a variety of hormones
	CHAPTER 23 Protein Turnover and Amino Acid Catabolism
		23.1 Proteins are Degraded to Amino Acids
			The digestion of dietary proteins begins in the stomach and is completed in the intestine
			Cellular proteins are degraded at different rates
		23.2 Protein Turnover Is Tightly Regulated
			Ubiquitin tags proteins for destruction
			The proteasome digests the ubiquitin-tagged proteins
			The ubiquitin pathway and the proteasome have prokaryotic counterparts
			Protein degradation can be used to regulate biological function
		23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen
			Alpha-amino groups are converted into ammonium ions by the oxidative deamination of glutamate
			Mechanism: Pyridoxal phosphate forms Schiff-base intermediates in aminotransferases
			Aspartate aminotransferase is an archetypal pyridoxal-dependent transaminase
			Blood levels of aminotransferases serve a diagnostic function
			Pyridoxal phosphate enzymes catalyze a wide array of reactions
			Serine and threonine can be directly deaminated
			Peripheral tissues transport nitrogen to the liver
		23.4 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates
			The urea cycle begins with the formation of carbamoyl phosphate
			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
			Urea-cycle enzymes are evolutionarily related to enzymes in other metabolic pathways
			Inherited defects of the urea cycle cause hyperammonemia and can lead to brain damage
			Urea is not the only means of disposing of excess nitrogen
		23.5 Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates
			Pyruvate is an entry point into metabolism for a number of amino acids
			Oxaloacetate is an entry point into metabolism for aspartate and asparagine
			Alpha-ketoglutarate is an entry point into metabolism for five-carbon amino acids
			Succinyl coenzyme A is a point of entry for several nonpolar amino acids
			Methionine degradation requires the formation of a key methyl donor, S-adenosylmethionine
			The branched-chain amino acids yield acetyl CoA, acetoacetate, or propionyl CoA
			Oxygenases are required for the degradation of aromatic amino acids
		23.6 Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation
			Phenylketonuria is one of the most common metabolic disorders
			Determining the basis of the neurological symptoms of phenylketonuria is an active area of research
Part III SYNTHESIZING THE MOLECULES OF LIFE
	CHAPTER 24 The Biosynthesis of Amino Acids
		Amino acid synthesis requires solutions to three key biochemical problems
		24.1 Nitrogen Fixation: Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia
			The iron–molybdenum cofactor of nitrogenase binds and reduces atmospheric nitrogen
			Ammonium ion is assimilated into an amino acid through glutamate and glutamine
		24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways
			Human beings can synthesize some amino acids but must obtain others from their diet
			Aspartate, alanine, and glutamate are formed by the addition of an amino group to an alpha-ketoacid
			A common step determines the chirality of all amino acids
			The formation of asparagine from aspartate requires an adenylated intermediate
			Glutamate is the precursor of glutamine, proline, and arginine
			3-Phosphoglycerate is the precursor of serine, cysteine, and glycine
			Tetrahydrofolate carries activated one-carbon units at several oxidation levels
			S-Adenosylmethionine is the major donor of methyl groups
			Cysteine is synthesized from serine and homocysteine
			High homocysteine levels correlate with vascular disease
			Shikimate and chorismate are intermediates in the biosynthesis of aromatic amino acids
			Tryptophan synthase illustrates substrate channeling in enzymatic catalysis
		24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis
			Branched pathways require sophisticated regulation
			The sensitivity of glutamine synthetase to allosteric regulation is altered by covalent modification
		24.4 Amino Acids Are Precursors of Many Biomolecules
			Glutathione, a gamma-glutamyl peptide, serves as a sulfhydryl buffer and an antioxidant
			Nitric oxide, a short-lived signal molecule, is formed from arginine
			Porphyrins are synthesized from glycine and succinyl coenzyme A
			Porphyrins accumulate in some inherited disorders of porphyrin metabolism
	CHAPTER 25 Nucleotide Biosynthesis
		Nucleotides can be synthesized by de novo or salvage pathways
		25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways
			Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation
			The side chain of glutamine can be hydrolyzed to generate ammonia
			Intermediates can move between active sites by channeling
			Orotate acquires a ribose ring from PRPP to form a pyrimidine nucleotide and is converted into uridylate
			Nucleotide mono-, di-, and triphosphates are interconvertible
			CTP is formed by amination of UTP
			Salvage pathways recycle pyrimidine bases
		25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways
			The purine ring system is assembled on ribose phosphate
			The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement
			AMP and GMP are formed from IMP
			Enzymes of the purine synthesis pathway associate with one another in vivo
			Salvage pathways economize intracellular energy expenditure
		25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism
			Mechanism: A tyrosyl radical is critical to the action of ribonucleotide reductase
			Stable radicals other than tyrosyl radical are employed by other ribonucleotide reductases
			Thymidylate is formed by the methylation of deoxyuridylate
			Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate, a one-carbon carrier
			Several valuable anticancer drugs block the synthesis of thymidylate
		25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition
			Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase
			The synthesis of purine nucleotides is controlled by feedback inhibition at several sites
			The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase
		25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions
			The loss of adenosine deaminase activity results in severe combined immunodeficiency
			Gout is induced by high serum levels of urate
			Lesch–Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme
			Folic acid deficiency promotes birth defects such as spina bifida
	CHAPTER 26 The Biosynthesis of Membrane Lipids and Steroids
		26.1 Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols
			The synthesis of phospholipids requires an activated intermediate
			Some phospholipids are synthesized from an activated alcohol
			Phosphatidylcholine is an abundant phospholipid
			Excess choline is implicated in the development of heart disease
			Base-exchange reactions can generate phospholipids
			Sphingolipids are synthesized from ceramide
			Gangliosides are carbohydrate-rich sphingolipids that contain acidic sugars
			Sphingolipids confer diversity on lipid structure and function
			Respiratory distress syndrome and Tay–Sachs disease result from the disruption of lipid metabolism
			Ceramide metabolism stimulates tumor growth
			Phosphatidic acid phosphatase is a key regulatory enzyme in lipid metabolism
		26.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages
			The synthesis of mevalonate, which is activated as isopentenyl pyrophosphate, initiates the synthesis of cholesterol
			Squalene (C30) is synthesized from six molecules of isopentenyl pyrophosphate (C5)
			Squalene cyclizes to form cholesterol
		26.3 The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels
			Lipoproteins transport cholesterol and triacylglycerols throughout the organism
			Low-density lipoproteins play a central role in cholesterol metabolism
			The absence of the LDL receptor leads to hypercholesterolemia and atherosclerosis
			Mutations in the LDL receptor prevent LDL release and result in receptor destruction
			Cycling of the LDL receptor is regulated
			HDL appears to protect against atherosclerosis
			The clinical management of cholesterol levels can be understood at a biochemical level
		26.4 Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones
			Letters identify the steroid rings and numbers identify the carbon atoms
			Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2
			The cytochrome P450 system is widespread and performs a protective function
			Pregnenolone, a precursor of many other steroids, is formed from cholesterol by cleavage of its side chain
			Progesterone and corticosteroids are synthesized from pregnenolone
			Androgens and estrogens are synthesized from pregnenolone
			Vitamin D is derived from cholesterol by the ringsplitting activity of light
	CHAPTER 27 The Integration of Metabolism
		27.1 Caloric Homeostasis Is a Means of Regulating Body Weight
		27.2 The Brain Plays a Key Role in Caloric Homeostasis
			Signals from the gastrointestinal tract induce feelings of satiety
			Leptin and insulin regulate long-term control over caloric homeostasis
			Leptin is one of several hormones secreted by adipose tissue
			Leptin resistance may be a contributing factor to obesity
			Dieting is used to combat obesity
		27.3 Diabetes Is a Common Metabolic Disease Often Resulting from Obesity
			Insulin initiates a complex signal-transduction pathway in muscle
			Metabolic syndrome often precedes type 2 diabetes
			Excess fatty acids in muscle modify metabolism
			Insulin resistance in muscle facilitates pancreatic failure
			Metabolic derangements in type 1 diabetes result from insulin insufficiency and glucagon excess
		27.4 Exercise Beneficially Alters the Biochemistry of Cells
			Mitochondrial biogenesis is stimulated by muscular activity
			Fuel choice during exercise is determined by the intensity and duration of activity
		27.5 Food Intake and Starvation Induce Metabolic Changes
			The starved–fed cycle is the physiological response to a fast
			Metabolic adaptations in prolonged starvation minimize protein degradation
		27.6 Ethanol Alters Energy Metabolism in the Liver
			Ethanol metabolism leads to an excess of NADH
			Excess ethanol consumption disrupts vitamin metabolism
	CHAPTER 28 DNA Replication, Repair, and Recombination
		28.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template
			DNA polymerases require a template and a primer
			All DNA polymerases have structural features in common
			Two bound metal ions participate in the polymerase reaction
			The specificity of replication is dictated by complementarity of shape between bases
			An RNA primer synthesized by primase enables DNA synthesis to begin
			One strand of DNA is made continuously, whereas the other strand is synthesized in fragments
			DNA ligase joins ends of DNA in duplex regions
			The separation of DNA strands requires specific helicases and ATP hydrolysis
		28.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases
			The linking number of DNA, a topological property, determines the degree of supercoiling
			Topoisomerases prepare the double helix for unwinding
			Type I topoisomerases relax supercoiled structures
			Type II topoisomerases can introduce negative supercoils through coupling to ATP hydrolysis
		28.3 DNA Replication Is Highly Coordinated
			DNA replication requires highly processive polymerases
			The leading and lagging strands are synthesized in a coordinated fashion
			DNA replication in Escherichia coli begins at a unique site
			DNA synthesis in eukaryotes is initiated at multiple sites
			Telomeres are unique structures at the ends of linear chromosomes
			Telomeres are replicated by telomerase, a specialized polymerase that carries its own RNA template
		28.4 Many Types of DNA Damage Can Be Repaired
			Errors can arise in DNA replication
			Bases can be damaged by oxidizing agents, alkylating agents, and light
			DNA damage can be detected and repaired by a variety of systems
			The presence of thymine instead of uracil in DNA permits the repair of deaminated cytosine
			Some genetic diseases are caused by the expansion of repeats of three nucleotides
			Many cancers are caused by the defective repair of DNA
			Many potential carcinogens can be detected by their mutagenic action on bacteria
		28.5 DNA Recombination Plays Important Roles in Replication, Repair, and Other Processes
			RecA can initiate recombination by promoting strand invasion
			Some recombination reactions proceed through Holliday-junction intermediates
	CHAPTER 29 RNA Synthesis and Processing
		RNA synthesis comprises three stages: Initiation, elongation, and termination
		29.1 RNA Polymerases Catalyze Transcription
			RNA chains are formed de novo and grow in the 5\'-to-3\' direction
			RNA polymerases backtrack and correct errors
			RNA polymerase binds to promoter sites on the DNA template to initiate transcription
			Sigma subunits of RNA polymerase recognize promoter sites
			RNA polymerases must unwind the template double helix for transcription to take place
			Elongation takes place at transcription bubbles that move along the DNA template
			Sequences within the newly transcribed RNA signal termination
			Some messenger RNAs directly sense metabolite concentrations
			The rho protein helps to terminate the transcription of some genes
			Some antibiotics inhibit transcription
			Precursors of transfer and ribosomal RNA are cleaved and chemically modified after transcription in prokaryotes
		29.2 Transcription in Eukaryotes Is Highly Regulated
			Three types of RNA polymerase synthesize RNA in eukaryotic cells
			Three common elements can be found in the RNA polymerase II promoter region
			The TFIID protein complex initiates the assembly of the active transcription complex
			Multiple transcription factors interact with eukaryotic promoters
			Enhancer sequences can stimulate transcription at start sites thousands of bases away
		29.3 The Transcription Products of Eukaryotic Polymerases Are Processed
			RNA polymerase I produces three ribosomal RNAs
			RNA polymerase III produces transfer RNA
			The product of RNA polymerase II, the pre-mRNA transcript, acquires a 5\' cap and a 3\' poly(A) tail
			Small regulatory RNAs are cleaved from larger precursors
			RNA editing changes the proteins encoded by mRNA
			Sequences at the ends of introns specify splice sites in mRNA precursors
			Splicing consists of two sequential transesterification reactions
			Small nuclear RNAs in spliceosomes catalyze the splicing of mRNA precursors
			Transcription and processing of mRNA are coupled
			Mutations that affect pre-mRNA splicing cause disease
			Most human pre-mRNAS can be spliced in alternative ways to yield different proteins
		29.4 The Discovery of Catalytic RNA was Revealing in Regard to Both Mechanism and Evolution
	CHAPTER 30 Protein Synthesis
		30.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences
			The synthesis of long proteins requires a low error frequency
			Transfer RNA molecules have a common design
			Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing
		30.2 Aminoacyl Transfer RNA Synthetases Read the Genetic Code
			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 various features of transfer RNA molecules
			Aminoacyl-tRNA synthetases can be divided into two classes
		30.3 The Ribosome Is the Site of Protein Synthesis
			Ribosomal RNAs (5S, 16S, and 23S rRNA) play a central role in protein synthesis
			Ribosomes have three tRNA-binding sites that bridge the 30S and 50S subunits
			The start signal is usually AUG preceded by several bases that pair with 16S rRNA
			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
			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
		30.4 Eukaryotic Protein Synthesis Differs from Bacterial Protein Synthesis Primarily in Translation Initiation
			Mutations in initiation factor 2 cause a curious pathological condition
		30.5 A Variety of Antibiotics and Toxins Can Inhibit Protein Synthesis
			Some antibiotics inhibit protein synthesis
			Diphtheria toxin blocks protein synthesis in eukaryotes by inhibiting translocation
			Ricin fatally modifies 28S ribosomal RNA
		30.6 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
			Transport vesicles carry cargo proteins to their final destination
	CHAPTER 31 The Control of Gene Expression in Prokaryotes
		31.1 Many DNA-Binding Proteins Recognize Specific DNA Sequences
			The helix-turn-helix motif is common to many prokaryotic DNA-binding proteins
		31.2 Prokaryotic DNA-Binding Proteins Bind Specifically to Regulatory Sites in Operons
			An operon consists of regulatory elements and protein-encoding genes
			The lac repressor protein in the absence of lactose binds to the operator and blocks transcription
			Ligand binding can induce structural changes in regulatory proteins
			The operon is a common regulatory unit in prokaryotes
			Transcription can be stimulated by proteins that contact RNA polymerase
		31.3 Regulatory Circuits Can Result in Switching Between Patterns of Gene Expression
			The λ repressor regulates its own expression
			A circuit based on the λ repressor and Cro forms a genetic switch
			Many prokaryotic cells release chemical signals that regulate gene expression in other cells
			Biofilms are complex communities of prokaryotes
		31.4 Gene Expression Can Be Controlled at Posttranscriptional Levels
			Attenuation is a prokaryotic mechanism for regulating transcription through the modulation of nascent RNA secondary structure
	CHAPTER 32 The Control of Gene Expression in Eukaryotes
		32.1 Eukaryotic DNA Is Organized into Chromatin
			Nucleosomes are complexes of DNA and histones
			DNA wraps around histone octamers to form nucleosomes
		32.2 Transcription Factors Bind DNA and Regulate Transcription Initiation
			A range of DNA-binding structures are employed by eukaryotic DNA-binding proteins
			Activation domains interact with other proteins
			Multiple transcription factors interact with eukaryotic regulatory regions
			Enhancers can stimulate transcription in specific cell types
			Induced pluripotent stem cells can be generated by introducing four transcription factors into differentiated cells
		32.3 The Control of Gene Expression Can Require Chromatin Remodeling
			The methylation of DNA can alter patterns of gene expression
			Steroids and related hydrophobic molecules pass through membranes and bind to DNA-binding receptors
			Nuclear hormone receptors regulate transcription by recruiting coactivators to the transcription complex
			Steroid-hormone receptors are targets for drugs
			Chromatin structure is modulated through covalent modifications of histone tails
			Histone deacetylases contribute to transcriptional repression
		32.4 Eukaryotic Gene Expression Can Be Controlled at Posttranscriptional Levels
			Genes associated with iron metabolism are translationally regulated in animals
			Small RNAs regulate the expression of many eukaryotic genes
Part IV RESPONDING TO ENVIRONMENTAL CHANGES
	CHAPTER 33 Sensory Systems
		33.1 A Wide Variety of Organic Compounds Are Detected by Olfaction
			Olfaction is mediated by an enormous family of seven-transmembrane-helix receptors
			Odorants are decoded by a combinatorial mechanism
		33.2 Taste Is a Combination of Senses That Function by Different Mechanisms
			Sequencing of the human genome led to the discovery of a large family of 7TM bitter receptors
			A heterodimeric 7TM receptor responds to sweet compounds
			Umami, the taste of glutamate and aspartate, is mediated by a heterodimeric receptor related to the sweet receptor
			Salty tastes are detected primarily by the passage of sodium ions through channels
			Sour tastes arise from the effects of hydrogen ions (acids) on channels
		33.3 Photoreceptor Molecules in the Eye Detect Visible Light
			Rhodopsin, a specialized 7TM receptor, absorbs visible light
			Light absorption induces a specific isomerization of bound 11-cis-retinal
			Light-induced lowering of the calcium level coordinates recovery
			Color vision is mediated by three cone receptors that are homologs of rhodopsin
			Rearrangements in the genes for the green and red pigments lead to “color blindness”
		33.4 Hearing Depends on the Speedy Detection of Mechanical Stimuli
			Hair cells use a connected bundle of stereocilia to detect tiny motions
			Mechanosensory channels have been identified in Drosophila and vertebrates
		33.5 Touch Includes the Sensing of Pressure, Temperature, and Other Factors
			Studies of capsaicin reveal a receptor for sensing high temperatures and other painful stimuli
	CHAPTER 34 The Immune System
		Innate immunity is an evolutionarily ancient defense system
		The adaptive immune system responds by using the principles of evolution
		34.1 Antibodies Possess Distinct Antigen-Binding and Effector Units
		34.2 Antibodies Bind Specific Molecules Through Hypervariable Loops
			The immunoglobulin fold consists of a beta-sandwich framework with hypervariable loops
			X-ray analyses have revealed how antibodies bind antigens
			Large antigens bind antibodies with numerous interactions
		34.3 Diversity Is Generated by Gene Rearrangements
			J (joining) genes and D (diversity) genes increase antibody diversity
			More than 108 antibodies can be formed by combinatorial association and somatic mutation
			The oligomerization of antibodies expressed on the surfaces of immature B cells triggers antibody secretion
			Different classes of antibodies are formed by the hopping of VH genes
		34.4 Major-Histocompatibility-Complex Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors
			Peptides presented by MHC proteins occupy a deep groove flanked by alpha helices
			T-cell receptors are antibody-like proteins containing variable and constant regions
			CD8 on cytotoxic T cells acts in concert with T-cell receptors
			Helper T cells stimulate cells that display foreign peptides bound to class II MHC proteins
			Helper T cells rely on the T-cell receptor and CD4 to recognize foreign peptides on antigen-presenting cells
			MHC proteins are highly diverse
			Human immunodeficiency viruses subvert the immune system by destroying helper T cells
		34.5 The Immune System Contributes to the Prevention and the Development of Human Diseases
			T cells are subjected to positive and negative selection in the thymus
			Autoimmune diseases result from the generation of immune responses against self-antigens
			The immune system plays a role in cancer prevention
			Vaccines are a powerful means to prevent and eradicate disease
	CHAPTER 35 Molecular Motors
		35.1 Most Molecular-Motor Proteins Are Members of the P-Loop NTPase Superfamily
			Molecular motors are generally oligomeric proteins with an ATPase core and an extended structure
			ATP binding and hydrolysis induce changes in the conformation and binding affinity of motor proteins
		35.2 Myosins Move Along Actin Filaments
			Actin is a polar, self-assembling, dynamic polymer
			Myosin head domains bind to actin filaments
			Motions of single motor proteins can be directly observed
			Phosphate release triggers the myosin power stroke
			Muscle is a complex of myosin and actin
			The length of the lever arm determines motor velocity
		35.3 Kinesin and Dynein Move Along Microtubules
			Microtubules are hollow cylindrical polymers
			Kinesin motion is highly processive
		35.4 A Rotary Motor Drives Bacterial Motion
			Bacteria swim by rotating their flagella
			Proton flow drives bacterial flagellar rotation
			Bacterial chemotaxis depends on reversal of the direction of flagellar rotation
	CHAPTER 36 Drug Development
		36.1 The Development of Drugs Presents Huge Challenges
			Drug candidates must be potent and selective modulators of their targets
			Drugs must have suitable properties to reach their targets
			Toxicity can limit drug effectiveness
		36.2 Drug Candidates Can Be Discovered by Serendipity, Screening, or Design
			Serendipitous observations can drive drug development
			Natural products are a valuable source of drugs and drug leads
			Screening libraries of synthetic compounds expands the opportunity for identification of drug leads
			Drugs can be designed on the basis of three-dimensional structural information about their targets
		36.3 Analyses of Genomes Hold Great Promise for Drug Discovery
			Potential targets can be identified in the human proteome
			Animal models can be developed to test the validity of potential drug targets
			Potential targets can be identified in the genomes of pathogens
			Genetic differences influence individual responses to drugs
		36.4 The Clinical Development of Drugs Proceeds Through Several Phases
			Clinical trials are time consuming and expensive
			The evolution of drug resistance can limit the utility of drugs for infectious agents and cancer
Answers to Problems
Selected Readings
Index
Back End paper
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