Biochemistry

About this Book
	Cover Page
	Title Page
	Copyright Page
	Dedication
	About the Authors
	Preface
	Molecular Evolution
	Clinical Applications
	Industrial Applications
	Biochemistry in Focus
	Acknowledgments
	Brief Contents
	Contents
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: Small Molecules
	Appendix: Functional Groups
	Key Terms
	Problems
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
	2.4 Tertiary Structure: Proteins Can Fold into Globular or Fibrous Structures
		Fibrous proteins provide structural support for cells and tissues
	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
		Posttranslational modifications confer new capabilities to proteins
	Summary
	Appendix: Visualizing Molecular Structures: Proteins
	Key Terms
	Problems
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 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
		Co-immunoprecipitation enables the identification of binding partners of a protein
		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, NMR Spectroscopy, and Cryo-Electron Microscopy
		X-ray crystallography reveals three-dimensional structure in atomic detail
		Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution
		Cryo-electron microscopy is an emerging method of protein structure determination
	Summary
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		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
		Unusual circular DNA exists in the eukaryotic nucleus
	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
	Summary
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
Chapter 7 Hemoglobin: Portrait of a Protein in Action
	7.1 Binding of Oxygen by Heme Iron
		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 α-hemoglobin chains is prevented
		Additional globins are encoded in the human genome
	Summary
	Appendix: Binding Models Can Be Formulated in Quantitative Terms: The Hill Plot and the Concerted Model
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
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
		Enzymes have impact outside the laboratory or clinic
	8.6 Enzymes Can Be Studied One Molecule at a Time
	Summary
	Appendix: Enzymes Are Classified on the Basis of the Types of Reactions That They Catalyze
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
	Summary
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		Mutations in Protein Kinase A Can Cause Cushing Syndrome
		Exercise modifies the phosphorylation of many proteins
	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
		Serpins can be degraded by a unique enzyme
		Blood clotting is accomplished by a cascade of zymogen activations
		Prothrombin must bind to Ca2+ to be converted to thrombin
		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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		Human milk oligosaccharides protect newborns from infection
	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
		Chitin can be processed to a molecule with a variety of uses
		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 and within cells
		Lectins are organized into different classes
		Influenza virus binds to sialic acid residues
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
Chapter 14 Signal-Transduction Pathways
	Signal transduction depends on molecular circuits
	14.1 Epinephrine and Angiotensin II Signaling: 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 Systems 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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
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
		ATP may have roles other than in energy and signal transduction
	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
	Summary
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		The enzymes of glycolysis are associated with one another
		Glycolysis can be divided into two parts
		Hexokinase traps glucose in the cell and begins glycolysis
		Fructose 1,6-bisphosphate is generated from glucose 6-phosphate
		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
		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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Biochemistry in Focus 1
	Appendix: Biochemistry in Focus 2
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		An enzyme in lipid metabolism is hijacked to inhibit pyruvate dehydrogenase activity
	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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Biochemistry in Focus 1
	Appendix: Biochemistry in Focus 2
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		Electron flow from NADH to molecular oxygen powers 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
		Most of the electron-transport chain is organized into a complex called the respirasome
		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
		Reintroduction of UCP-1 into pigs may be economically valuable
		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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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 oxidative phase 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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Biochemistry in Focus 1
	Appendix: Biochemistry in Focus 2
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		An isozymic form of glycogen phosphorylase exists in the brain
	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 concentration
		A biochemical understanding of glycogen-storage diseases is possible
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		Some fatty acids may contribute to the development of pathological conditions
	22.4 Ketone Bodies Are a Fuel Source Derived from Fats
		Ketone bodies are a major fuel in some tissues
		Animals cannot convert fatty acids into glucose
	22.5 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
		Triacylglycerols may become an important renewal energy source
	22.6 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
	22.7 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
		AMP-activated protein kinase is a key regulator of metabolism
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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 amino acids
		Methionine degradation requires the formation of a key methyl donor, S-adenosylmethionine
		Threonine deaminase initiates the degradation of threonine
		The branched-chain amino acids yield acetyl CoA, acetoacetate, or propionyl CoA
		Oxygenases are required for the degradation of aromatic amino acids
		Protein metabolism helps to power the flight of migratory birds
	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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		Amino acids are precursors for a number of neurotransmitters
		Porphyrins are synthesized from glycine and succinyl coenzyme A
		Porphyrins accumulate in some inherited disorders of porphyrin metabolism
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
		Inability to transport cholesterol from the lysosome causes Niemann-Pick disease
		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 Biochemicals Are Synthesized from Cholesterol and Isoprene
		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 ring-splitting activity of light
		Five-carbon units are joined to form a wide variety of biomolecules
		Some isoprenoids have industrial applications
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Biochemistry in Focus 1
	Appendix: Biochemistry in Focus 2
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
Chapter 28 Drug Development
	28.1 Compounds Must Meet Stringent Criteria to Be Developed into Drugs
		Drugs must be potent and selective
		Drugs must have suitable properties to reach their targets
		Toxicity can limit drug effectiveness
	28.2 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
	28.3 Genomic Analyses Can Aid 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
	28.4 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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 29 DNA Replication, Repair, and Recombination
	29.1 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
	29.2 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
	29.3 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 and proceeds through initiation, elongation, and termination
		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
	29.4 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
	29.5 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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 30 RNA Synthesis and Processing
	RNA synthesis comprises three stages: Initiation, elongation, and termination
	30.1 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
	30.2 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
	30.3 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
	30.4 The Discovery of Catalytic RNA Was Revealing in Regard to Both Mechanism and Evolution
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 31 Protein Synthesis
	31.1 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
	31.2 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
	31.3 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
	31.4 Eukaryotic Protein Synthesis Differs from Bacterial Protein Synthesis Primarily in Translation Initiation
		Mutations in initiation factor 2 cause a curious pathological condition
	31.5 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
		Some toxins modifiy 28S ribosomal RNA
	31.6 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
	Summary
	Appendix: Biochemistry in Focus
	Appendix: Problem-Solving Strategies
	Key Terms
	Problems
Chapter 32 The Control of Gene Expression in Prokaryotes
	32.1 Many DNA-Binding Proteins Recognize Specific DNA Sequences
		The helix-turn-helix motif is common to many prokaryotic DNA-binding proteins
	32.2 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
	32.3 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
	32.4 Gene Expression Can Be Controlled at Posttranscriptional Levels
		Attenuation is a prokaryotic mechanism for regulating transcription through the modulation of nascent RNA secondary structure
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 33 The Control of Gene Expression in Eukaryotes
	33.1 Eukaryotic DNA Is Organized into Chromatin
		Nucleosomes are complexes of DNA and histones
		DNA wraps around histone octamers to form nucleosomes
	33.2 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
	33.3 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
		Transcriptional repression can be achieved through histone deacetylation and other modifications
	33.4 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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 34 Sensory Systems
	34.1 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
	34.2 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
	34.3 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”
	34.4 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
	34.5 Touch Includes the Sensing of Pressure, Temperature, and Other Factors
		Studies of capsaicin reveal a receptor for sensing high temperatures and other painful stimuli
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 35 The Immune System
	Innate immunity is an evolutionarily ancient defense system
	The adaptive immune system responds by using the principles of evolution
	35.1 Antibodies Possess Distinct Antigen-Binding and Effector Units
	35.2 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
	35.3 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
	35.4 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
	35.5 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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Chapter 36 Molecular Motors
	36.1 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
	36.2 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
	36.3 Kinesin and Dynein Move Along Microtubules
		Microtubules are hollow cylindrical polymers
		Kinesin motion is highly processive
	36.4 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
	Summary
	Appendix: Biochemistry in Focus
	Key Terms
	Problems
Answers to Problems
Selected Readings
Index
Acidity Constants
Standard Bond Lengths
Backcover
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