Biochemistry

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: Small Molecules
APPENDIX  Functional Groups

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 〈 helices, ® 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 
APPENDIX  Visualizing Molecular Structures: Proteins

Chapter 3 Exploring Proteins and Proteomes
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
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
APPENDIX  Problem-Solving Strategies

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
APPENDIX  Problem-Solving Strategies
 
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 ⎣ 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
APPENDIX  Biochemistry in Focus: Improved biofuel production from genetically-engineered algae
 
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
APPENDIX  Biochemistry in Focus: Using sequence alignments to identify functionally important residues
APPENDIX  Problem-Solving Strategies
 
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 〈1®1–〈2®2 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
APPENDIX  Biochemistry in Focus: A potential antidote for carbon monoxide poisoning?
 
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 
APPENDIX  Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze
APPENDIX  Problem-Solving Strategies
APPENDIX  Biochemistry in Focus: The effect of temperature rate on enzyme-catalyzed reactions and the coloring of Siamese cats

Chapter 9 Catalytic Strategies
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
APPENDIX  Problem-Solving Strategies
 
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 ©-carboxyglutamate 
The clotting process must be precisely regulated 
Hemophilia revealed an early step in clotting
APPENDIX  Biochemistry in Focus: Phosphoribosylpyrophosphate synthetase-induced gout
APPENDIX  Problem-Solving Strategies
 
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
APPENDIX  Biochemistry in Focus: α-Glucosidase (maltase) inhibitors can help to maintain blood glucose homeostsis
 
Chapter 12 Lipids and Cell 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
APPENDIX  Biochemistry in Focus: The curious case of cardiolipin

Chapter 13 Membrane Channels and Pumps
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
APPENDIX  Biochemistry in Focus: Setting the pace is more than funny business
APPENDIX  Problem-Solving Strategies

Chapter 14 Signal-Transduction Pathways
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 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 
APPENDIX  Biochemistry in Focus: Gases get in on the signaling game

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 
APPENDIX  Problem-Solving Strategies

Chapter 16 Glycolysis and Gluconeogenesis
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 
APPENDIX  Biochemistry in Focus: Triose phosphate isomerase deficiency (TPID)
APPENDIX  Biochemistry in Focus: Pyruvate carboxylase deficiency (PCD)
APPENDIX  Problem-Solving Strategies

Chapter 17 The Citric Acid Cycle
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
APPENDIX  Biochemistry in Focus: New treatments for tuberculosis may be on the horizon
APPENDIX  Problem-Solving Strategies

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
Much 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
APPENDIX  Biochemistry in Focus: Leber hereditary optic neuropathy can result from defects in Complex I 

Chapter 19 The Light Reactions of Photosynthesis
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 
APPENDIX  Biochemistry in Focus: Increasing the efficiency of photosynthesis will increase crop yields
APPENDIX  Problem-Solving Strategies

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
APPENDIX  Biochemistry in Focus
APPENDIX  Biochemistry in Focus: Hummingbirds and the pentose phosphate pathway
APPENDIX  Problem-Solving Strategies
 
Chapter 21 Glycogen Metabolism
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 isomeric 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 〈-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
APPENDIX  Biochemistry in Focus: McArdle disease results from a lack of skeletal muscle glycogen phosphorylase
APPENDIX  Problem-Solving Strategies

Chapter 22 Fatty Acid Metabolism
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 renewable 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
APPENDIX  Biochemistry in Focus: Ethanol consumption results in triacylglycerol accumulation in the liver
APPENDIX  Problem-Solving Strategies

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
APPENDIX  Biochemistry in Focus: Methylmalonic acidemia results from an inborn error of metabolism
APPENDIX  Problem-Solving Strategies 

Part III SYNTHESIZING THE MOLECULES OF LIFE
Chapter 24 The Biosynthesis of Amino Acids
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
APPENDIX  Biochemistry in Focus: Tyrosine is a precursor for human pigments
APPENDIX  Problem-Solving Strategies 

Chapter 25 Nucleotide Biosynthesis
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
APPENDIX  Biochemistry in Focus: Uridine plays a role in caloric homeostasis
APPENDIX  Problem-Solving Strategies 

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
APPENDIX  Biochemistry in Focus: Excess ceramides may cause insulin insensitivity
APPENDIX  Problem-Solving Strategies

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
APPENDIX  Biochemistry in Focus: Adipokines help to regulate metabolism in the liver
APPENDIX  Biochemistry in Focus: Exercise alters muscle and whole-body metabolism
APPENDIX  Problem-Solving Strategies

Chapter 28 Drug Development
28.1 Compounds Must Meet Stringent Criteria to be Developed Into Drugs 
Drug 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
APPENDIX  Biochemistry in Focus: Monoclonal antibodies: Expanding the drug developer’s toolbox

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
APPENDIX  Biochemistry in Focus: Identifying amino acids crucial for DNA replication fidelity 

Chapter 30 RNA Synthesis and Processing 
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
APPENDIX  Biochemistry in Focus: Discovering enzymes made of RNA 

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 modify 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
APPENDIX  Biochemistry in Focus: Selective control of gene expression by ribosomes
APPENDIX  Problem-Solving Strategies 

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 ⎣ repressor regulates its own expression 
A circuit based on the ⎣ 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
APPENDIX  Biochemistry in Focus: Regulating gene expression through proteolysis 

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
APPENDIX  Biochemistry in Focus: A mechanism for consolidating epigenetic modifications 

Part IV RESPONDING TO ENVIRONMENTAL CHANGES (Online Only)
Chapter 34 Sensory Systems (Online Only)
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
APPENDIX  Biochemistry in Focus: Binding many palatable tastants with a single receptor

Chapter 35 The Immune System (Online Only)
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
APPENDIX  Biochemistry in Focus 

Chapter 36 Molecular Motors (Online Only)
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
 
Back Matter
Answers to Problems 
Selected Readings 
Index