| General note |
Table of Contents<br/>Part I THE MOLECULAR DESIGN OF LIFE<br/>Chapter 1 Biochemistry: An Evolving Science<br/>1.1 Biochemical Unity Underlies Biological Diversity <br/>1.2 DNA Illustrates the Interplay Between Form and Function <br/>DNA is constructed from four building blocks <br/>Two single strands of DNA combine to form a double helix <br/>DNA structure explains heredity and the storage of information <br/>1.3 Concepts from Chemistry Explain the Properties of Biological Molecules <br/>The formation of the DNA double helix as a key example <br/>The double helix can form from its component strands <br/>Covalent and noncovalent bonds are important for the structure and stability of biological molecules <br/>The double helix is an expression of the rules of chemistry <br/>The laws of thermodynamics govern the behavior of biochemical systems <br/>Heat is released in the formation of the double helix <br/>Acid–base reactions are central in many biochemical processes <br/>Acid–base reactions can disrupt the double helix<br/>Buffers regulate pH in organisms and in the laboratory <br/>1.4 The Genomic Revolution Is Transforming Biochemistry, Medicine, and Other Fields<br/>Genome sequencing has transformed biochemistry and other fields <br/>Environmental factors influence human biochemistry <br/>Genome sequences encode proteins and patterns of expression <br/>APPENDIX Visualizing Molecular Structures: Small Molecules<br/>APPENDIX Functional Groups<br/><br/>Chapter 2 Protein Composition and Structure<br/>2.1 Proteins Are Built from a Repertoire of 20 Amino Acids<br/>2.2 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains <br/>Proteins have unique amino acid sequences specified by genes <br/>Polypeptide chains are flexible yet conformationally restricted <br/>2.3 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops <br/>The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds <br/>Beta sheets are stabilized by hydrogen bonding between polypeptide strands <br/>Polypeptide chains can change direction by making reverse turns and loops <br/>2.4 Tertiary Structure: Proteins Can Fold into Globular or Fibrous Structures <br/>Fibrous proteins provide structural support for cells and tissues<br/>2.5 Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures <br/>2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure<br/>Amino acids have different propensities for forming 〈 helices, ® sheets, and turns <br/>Protein folding is a highly cooperative process <br/>Proteins fold by progressive stabilization of intermediates rather than by random search <br/>Prediction of three-dimensional structure from sequence remains a great challenge <br/>Some proteins are inherently unstructured and can exist in multiple conformations<br/>Protein misfolding and aggregation are associated with some neurological diseases<br/>Posttranslational modifications confer new capabilities to proteins <br/>APPENDIX Visualizing Molecular Structures: Proteins<br/><br/>Chapter 3 Exploring Proteins and Proteomes<br/>3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function <br/>The assay: How do we recognize the protein that we are looking for? <br/>Proteins must be released from the cell to be purified <br/>Proteins can be purified according to solubility, size, charge, and binding affinity <br/>Proteins can be separated by gel electrophoresis and displayed <br/>A protein purification scheme can be quantitatively evaluated <br/>Ultracentrifugation is valuable for separating biomolecules and determining their masses <br/>Protein purification can be made easier with the use of recombinant DNA technology <br/>3.2 Immunology Provides Important Techniques with Which to Investigate Proteins<br/>Antibodies to specific proteins can be generated <br/>Monoclonal antibodies with virtually any desired specificity can be readily prepared <br/>Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay <br/>Western blotting permits the detection of proteins separated by gel electrophoresis<br/>Co-immunoprecipitation enables the identification of binding partners of a protein <br/>Fluorescent markers make the visualization of proteins in the cell possible <br/>3.3 Mass Spectrometry Is a Powerful Technique for the Identification of Peptides and Proteins <br/>Peptides can be sequenced by mass spectrometry <br/>Proteins can be specifically cleaved into small peptides to facilitate analysis<br/>Genomic and proteomic methods are complementary <br/>The amino acid sequence of a protein provides valuable information <br/>Individual proteins can be identified by mass spectrometry <br/>3.4 Peptides Can Be Synthesized by Automated Solid-Phase Methods <br/>3.5 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography, NMR Spectroscopy, and Cryo-Electron Microscopy <br/>X-ray crystallography reveals three-dimensional structure in atomic detail <br/>Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution <br/>Cryo-electron microscopy is an emerging method of protein structure determination<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 4 DNA, RNA, and the Flow of Genetic Information<br/>4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar–Phosphate Backbone <br/>RNA and DNA differ in the sugar component and one of the bases <br/>Nucleotides are the monomeric units of nucleic acids <br/>DNA molecules are very long and have directionality <br/>4.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure <br/>The double helix is stabilized by hydrogen bonds and van der Waals interactions <br/>DNA can assume a variety of structural forms <br/>Some DNA molecules are circular and supercoiled <br/>Single-stranded nucleic acids can adopt elaborate structures <br/>4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information <br/>Differences in DNA density established the validity of the semiconservative replication hypothesis <br/>The double helix can be reversibly melted<br/>Unusual circular DNA exists in the eukaryotic nucleus <br/>4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates <br/>DNA polymerase catalyzes phosphodiester-bridge formation <br/>The genes of some viruses are made of RNA <br/>4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules <br/>Several kinds of RNA play key roles in gene expression <br/>All cellular RNA is synthesized by RNA polymerases <br/>RNA polymerases take instructions from DNA templates <br/>Transcription begins near promoter sites and ends at terminator sites <br/>Transfer RNAs are the adaptor molecules in protein synthesis <br/>4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point <br/>Major features of the genetic code <br/>Messenger RNA contains start and stop signals for protein synthesis <br/>The genetic code is nearly universal <br/>4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons <br/>RNA processing generates mature RNA <br/>Many exons encode protein domains<br/>APPENDIX Problem-Solving Strategies<br/> <br/>Chapter 5 Exploring Genes and Genomes <br/>5.1 The Exploration of Genes Relies on Key Tools<br/>Restriction enzymes split DNA into specific fragments <br/>Restriction fragments can be separated by gel electrophoresis and visualized <br/>DNA can be sequenced by controlled termination of replication <br/>DNA probes and genes can be synthesized by automated solid-phase methods <br/>Selected DNA sequences can be greatly amplified by the polymerase chain reaction <br/>PCR is a powerful technique in medical diagnostics, forensics, and studies of molecular evolution <br/>The tools for recombinant DNA technology have been used to identify disease-causing mutations <br/>5.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology <br/>Restriction enzymes and DNA ligase are key tools in forming recombinant DNA molecules <br/>Plasmids and ⎣ phage are choice vectors for DNA cloning in bacteria <br/>Bacterial and yeast artificial chromosomes <br/>Specific genes can be cloned from digests of genomic DNA <br/>Complementary DNA prepared from mRNA can be expressed in host cells <br/>Proteins with new functions can be created through directed changes in DNA <br/>Recombinant methods enable the exploration of the functional effects of disease-causing mutations <br/>5.3 Complete Genomes Have Been Sequenced and Analyzed <br/>The genomes of organisms ranging from bacteria to multicellular eukaryotes have been sequenced <br/>The sequence of the human genome has been completed <br/>Next-generation sequencing methods enable the rapid determination of a complete genome sequence <br/>Comparative genomics has become a powerful research tool <br/>5.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision <br/>Gene-expression levels can be comprehensively examined <br/>New genes inserted into eukaryotic cells can be efficiently expressed <br/>Transgenic animals harbor and express genes introduced into their germ lines <br/>Gene disruption and genome editing provide clues to gene function and opportunities for new therapies <br/>RNA interference provides an additional tool for disrupting gene expression <br/>Tumor-inducing plasmids can be used to introduce new genes into plant cells <br/>Human gene therapy holds great promise for medicine<br/>APPENDIX Biochemistry in Focus: Improved biofuel production from genetically-engineered algae<br/> <br/>Chapter 6 Exploring Evolution and Bioinformatics <br/>6.1 Homologs Are Descended from a Common Ancestor <br/>6.2 Statistical Analysis of Sequence Alignments Can Detect Homology <br/>The statistical significance of alignments can be estimated by shuffling <br/>Distant evolutionary relationships can be detected through the use of substitution matrices <br/>Databases can be searched to identify homologous sequences <br/>6.3 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships <br/>Tertiary structure is more conserved than primary structure <br/>Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments <br/>Repeated motifs can be detected by aligning sequences with themselves <br/>Convergent evolution illustrates common solutions to biochemical challenges <br/>Comparison of RNA sequences can be a source of insight into RNA secondary structures <br/>6.4 Evolutionary Trees Can Be Constructed on the Basis of Sequence Information <br/>Horizontal gene transfer events may explain unexpected branches of the evolutionary tree <br/>6.5 Modern Techniques Make the Experimental Exploration of Evolution Possible <br/>Ancient DNA can sometimes be amplified and sequenced <br/>Molecular evolution can be examined experimentally<br/>APPENDIX Biochemistry in Focus: Using sequence alignments to identify functionally important residues<br/>APPENDIX Problem-Solving Strategies<br/> <br/>Chapter 7 Hemoglobin: Portrait of a Protein in Action<br/>7.1 Binding of Oxygen by Heme Iron<br/>Changes in heme electronic structure upon oxygen binding are the basis for functional imaging studies <br/>The structure of myoglobin prevents the release of reactive oxygen species <br/>Human hemoglobin is an assembly of four myoglobin-like subunits <br/>7.2 Hemoglobin Binds Oxygen Cooperatively <br/>Oxygen binding markedly changes the quaternary structure of hemoglobin <br/>Hemoglobin cooperativity can be potentially explained by several models <br/>Structural changes at the heme groups are transmitted to the 〈1®1–〈2®2 interface <br/>2,3-Bisphosphoglycerate in red cells is crucial in determining the oxygen affinity of hemoglobin <br/>Carbon monoxide can disrupt oxygen transport by hemoglobin <br/>7.3 Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen: The Bohr Effect <br/>7.4 Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease <br/>Sickle-cell anemia results from the aggregation of mutated deoxyhemoglobin molecules <br/>Thalassemia is caused by an imbalanced production of hemoglobin chains <br/>The accumulation of free alpha-hemoglobin chains is prevented <br/>Additional globins are encoded in the human genome <br/>APPENDIX Binding Models Can Be Formulated in Quantitative Terms: The Hill Plot and the Concerted Model<br/>APPENDIX Biochemistry in Focus: A potential antidote for carbon monoxide poisoning?<br/> <br/>Chapter 8 Enzymes: Basic Concepts and Kinetics<br/>8.1 Enzymes are Powerful and Highly Specific Catalysts <br/>Many enzymes require cofactors for activity <br/>Enzymes can transform energy from one form into another <br/>8.2 Gibbs Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes <br/>The free-energy change provides information about the spontaneity but not the rate of a reaction <br/>The standard free-energy change of a reaction is related to the equilibrium constant <br/>Enzymes alter only the reaction rate and not the reaction equilibrium <br/>8.3 Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State <br/>The formation of an enzyme–substrate complex is the first step in enzymatic catalysis <br/>The active sites of enzymes have some common features <br/>The binding energy between enzyme and substrate is important for catalysis <br/>8.4 The Michaelis–Menten Model Accounts for the Kinetic Properties of Many Enzymes <br/>Kinetics is the study of reaction rates <br/>The steady-state assumption facilitates a description of enzyme kinetics <br/>Variations in KM can have physiological consequences <br/>KM and Vmax values can be determined by several means <br/>KM and Vmax values are important enzyme characteristics <br/>kcat/KM is a measure of catalytic efficiency <br/>Most biochemical reactions include multiple substrates <br/>Allosteric enzymes do not obey Michaelis–Menten kinetics <br/>8.5 Enzymes Can Be Inhibited by Specific Molecules <br/>The different types of reversible inhibitors are kinetically distinguishable <br/>Irreversible inhibitors can be used to map the active site <br/>Penicillin irreversibly inactivates a key enzyme in bacterial cell-wall synthesis <br/>Transition-state analogs are potent inhibitors of enzymes <br/>Enzymes have impact outside the laboratory or clinic <br/>8.6 Enzymes Can Be Studied One Molecule at a Time <br/>APPENDIX Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze<br/>APPENDIX Problem-Solving Strategies<br/>APPENDIX Biochemistry in Focus: The effect of temperature rate on enzyme-catalyzed reactions and the coloring of Siamese cats<br/><br/>Chapter 9 Catalytic Strategies<br/>9.1 Proteases Facilitate a Fundamentally Difficult Reaction <br/>Chymotrypsin possesses a highly reactive serine residue <br/>Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate <br/>Serine is part of a catalytic triad that also includes histidine and aspartate <br/>Catalytic triads are found in other hydrolytic enzymes <br/>The catalytic triad has been dissected by site-directed mutagenesis <br/>Cysteine, aspartyl, and metalloproteases are other major classes of peptide-cleaving enzymes <br/>Protease inhibitors are important drugs <br/>9.2 Carbonic Anhydrases Make a Fast Reaction Faster <br/>Carbonic anhydrase contains a bound zinc ion essential for catalytic activity<br/>Catalysis entails zinc activation of a water molecule <br/>A proton shuttle facilitates rapid regeneration of the active form of the enzyme <br/>9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions <br/>Cleavage is by in-line displacement of 3′-oxygen from phosphorus by magnesium-activated water <br/>Restriction enzymes require magnesium for catalytic activity <br/>The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules, ensuring specificity <br/>Host-cell DNA is protected by the addition of methyl groups to specific bases <br/>Type II restriction enzymes have a catalytic core in common and are probably related by horizontal gene transfer <br/>9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work <br/>ATP hydrolysis proceeds by the attack of water on the gamma phosphoryl group <br/>Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change <br/>The altered conformation of myosin persists for a substantial period of time <br/>Scientists can watch single molecules of myosin move <br/>Myosins are a family of enzymes containing P-loop structures<br/>APPENDIX Problem-Solving Strategies<br/> <br/>Chapter 10 Regulatory Strategies<br/>10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway <br/>Allosterically regulated enzymes do not follow Michaelis–Menten kinetics <br/>ATCase consists of separable catalytic and regulatory subunits <br/>Allosteric interactions in ATCase are mediated by large changes in quaternary structure <br/>Allosteric regulators modulate the T-to-R equilibrium <br/>10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages <br/>10.3 Covalent Modification Is a Means of Regulating Enzyme Activity <br/>Kinases and phosphatases control the extent of protein phosphorylation <br/>Phosphorylation is a highly effective means of regulating the activities of target proteins <br/>Cyclic AMP activates protein kinase A by altering the quaternary structure<br/>Mutations in protein kinase A can cause Cushing Syndrome <br/>Exercise modifies the phosphorylation of many proteins <br/>10.4 Many Enzymes Are Activated by Specific Proteolytic Cleavage <br/>Chymotrypsinogen is activated by specific cleavage of a single peptide bond <br/>Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site <br/>The generation of trypsin from trypsinogen leads to the activation of other zymogens <br/>Some proteolytic enzymes have specific inhibitors<br/>Serpins can be degraded by a unique enzyme <br/>Blood clotting is accomplished by a cascade of zymogen activations <br/>Prothrombin must bind to Ca2+ to be converted to thrombin <br/>Fibrinogen is converted by thrombin into a fibrin clot <br/>Vitamin K is required for the formation of ©-carboxyglutamate <br/>The clotting process must be precisely regulated <br/>Hemophilia revealed an early step in clotting<br/>APPENDIX Biochemistry in Focus: Phosphoribosylpyrophosphate synthetase-induced gout<br/>APPENDIX Problem-Solving Strategies<br/> <br/>Chapter 11 Carbohydrates <br/>11.1 Monosaccharides Are the Simplest Carbohydrates<br/>Many common sugars exist in cyclic forms <br/>Pyranose and furanose rings can assume different conformations <br/>Glucose is a reducing sugar <br/>Monosaccharides are joined to alcohols and amines through glycosidic bonds <br/>Phosphorylated sugars are key intermediates in energy generation and biosyntheses <br/>11.2 Monosaccharides Are Linked to Form Complex Carbohydrates<br/>Sucrose, lactose, and maltose are the common disaccharides <br/>Glycogen and starch are storage forms of glucose <br/>Cellulose, a structural component of plants, is made of chains of glucose<br/>Human milk oligosaccharides protect newborns from infection <br/>11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins <br/>Carbohydrates can be linked to proteins through asparagine (N-linked) or through serine or threonine (O-linked) residues <br/>The glycoprotein erythropoietin is a vital hormone <br/>Glycosylation functions in nutrient sensing <br/>Proteoglycans, composed of polysaccharides and protein, have important structural roles <br/>Proteoglycans are important components of cartilage <br/>Mucins are glycoprotein components of mucus<br/>Chitin can be processed to a molecule with a variety of uses <br/>Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex <br/>Specific enzymes are responsible for oligosaccharide assembly <br/>Blood groups are based on protein glycosylation patterns <br/>Errors in glycosylation can result in pathological conditions <br/>Oligosaccharides can be “sequenced” <br/>11.4 Lectins Are Specific Carbohydrate-Binding Proteins <br/>Lectins promote interactions between cells and within cells <br/>Lectins are organized into different classes <br/>Influenza virus binds to sialic acid residues<br/>APPENDIX Biochemistry in Focus: α-Glucosidase (maltase) inhibitors can help to maintain blood glucose homeostsis<br/> <br/>Chapter 12 Lipids and Cell Membranes<br/>12.1 Fatty Acids Are Key Constituents of Lipids <br/>Fatty acid names are based on their parent hydrocarbons <br/>Fatty acids vary in chain length and degree of unsaturation <br/>12.2 There Are Three Common Types of Membrane Lipids <br/>Phospholipids are the major class of membrane lipids <br/>Membrane lipids can include carbohydrate moieties <br/>Cholesterol is a lipid based on a steroid nucleus <br/>Archaeal membranes are built from ether lipids with branched chains <br/>A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety <br/>12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media <br/>Lipid vesicles can be formed from phospholipids <br/>Lipid bilayers are highly impermeable to ions and most polar molecules <br/>12.4 Proteins Carry Out Most Membrane Processes <br/>Proteins associate with the lipid bilayer in a variety of ways <br/>Proteins interact with membranes in a variety of ways <br/>Some proteins associate with membranes through covalently attached hydrophobic groups<br/>Transmembrane helices can be accurately predicted from amino acid sequences <br/>12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane <br/>The fluid mosaic model allows lateral movement but not rotation through the membrane <br/>Membrane fluidity is controlled by fatty acid composition and cholesterol content <br/>Lipid rafts are highly dynamic complexes formed between cholesterol and specific lipids <br/>All biological membranes are asymmetric <br/>12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes<br/>APPENDIX Biochemistry in Focus: The curious case of cardiolipin<br/><br/>Chapter 13 Membrane Channels and Pumps<br/>13.1 The Transport of Molecules Across a Membrane May Be Active or Passive <br/>Many molecules require protein transporters to cross membranes <br/>Free energy stored in concentration gradients can be quantified <br/>13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes <br/>P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes <br/>Digitalis specifically inhibits the Na+–K+ pump by blocking its dephosphorylation <br/>P-type ATPases are evolutionarily conserved and play a wide range of roles <br/>Multidrug resistance highlights a family of membrane pumps with ATP-binding cassette domains <br/>13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another <br/>13.4 Specific Channels Can Rapidly Transport Ions Across Membranes <br/>Action potentials are mediated by transient changes in Na+ and K+ permeability <br/>Patch-clamp conductance measurements reveal the activities of single channels <br/>The structure of a potassium ion channel is an archetype for many ion-channel structures <br/>The structure of the potassium ion channel reveals the basis of ion specificity <br/>The structure of the potassium ion channel explains its rapid rate of transport <br/>Voltage gating requires substantial conformational changes in specific ion-channel domains <br/>A channel can be inactivated by occlusion of the pore: the ball-and-chain model <br/>The acetylcholine receptor is an archetype for ligand-gated ion channels <br/>Action potentials integrate the activities of several ion channels working in concert <br/>Disruption of ion channels by mutations or chemicals can be potentially life-threatening <br/>13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells <br/>13.6 Specific Channels Increase the Permeability of Some Membranes to Water<br/>APPENDIX Biochemistry in Focus: Setting the pace is more than funny business<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 14 Signal-Transduction Pathways<br/>14.1 Epinephrine and Angiotensin II Signaling: Heterotrimeric G Proteins Transmit Signals and Reset Themselves <br/>Ligand binding to 7TM receptors leads to the activation of heterotrimeric G proteins <br/>Activated G proteins transmit signals by binding to other proteins <br/>Cyclic AMP stimulates the phosphorylation of many target proteins by activating protein kinase A<br/>G proteins spontaneously reset themselves through GTP hydrolysis <br/>Some 7TM receptors activate the phosphoinositide cascade <br/>Calcium ion is a widely used second messenger <br/>Calcium ion often activates the regulatory protein calmodulin <br/>14.2 Insulin Signaling: Phosphorylation Cascades Are Central to Many Signal-Transduction Processes <br/>The insulin receptor is a dimer that closes around a bound insulin molecule <br/>Insulin binding results in the cross-phosphorylation and activation of the insulin receptor <br/>The activated insulin-receptor kinase initiates a kinase cascade <br/>Insulin signaling is terminated by the action of phosphatases <br/>14.3 EGF Signaling: Signal-Transduction Pathways Are Poised to Respond <br/>EGF binding results in the dimerization of the EGF receptor <br/>The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail <br/>EGF signaling leads to the activation of Ras, a small G protein <br/>Activated Ras initiates a protein kinase cascade <br/>EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras <br/>14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways <br/>14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases <br/>Monoclonal antibodies can be used to inhibit signal-transduction pathways activated in tumors <br/>Protein kinase inhibitors can be effective anticancer drugs <br/>Cholera and whooping cough are the result of altered G-protein activity <br/>APPENDIX Biochemistry in Focus: Gases get in on the signaling game<br/><br/><br/>Part II TRANSDUCING AND STORING ENERGY<br/>Chapter 15 Metabolism: Basic Concepts and Design<br/>15.1 Metabolism Is Composed of Many Coupled, Interconnecting Reactions <br/>Metabolism consists of energy-yielding and energy-requiring reactions <br/>A thermodynamically unfavorable reaction can be driven by a favorable reaction <br/>15.2 ATP Is the Universal Currency of Free Energy in Biological Systems <br/>ATP hydrolysis is exergonic <br/>ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions <br/>The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products <br/>Phosphoryl-transfer potential is an important form of cellular energy transformation <br/>15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy <br/>Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis <br/>Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis <br/>Phosphates play a prominent role in biochemical processes <br/>Energy from foodstuffs is extracted in three stages <br/>15.4 Metabolic Pathways Contain Many Recurring Motifs <br/>Activated carriers exemplify the modular design and economy of metabolism <br/>Many activated carriers are derived from vitamins <br/>Key reactions are reiterated throughout metabolism <br/>Metabolic processes are regulated in three principal ways <br/>Aspects of metabolism may have evolved from an RNA world <br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 16 Glycolysis and Gluconeogenesis<br/>16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms <br/>The enzymes of glycolysis are associated with one another<br/>Glycolysis can be divided into two parts<br/>Hexokinase traps glucose in the cell and begins glycolysis <br/>Fructose 1,6-bisphosphate is generated from glucose 6-phosphate <br/>The six-carbon sugar is cleaved into two three-carbon fragments <br/>Mechanism: Triose phosphate isomerase salvages a three-carbon fragment <br/>The oxidation of an aldehyde to an acid powers the formation of a compound with high phosphoryl-transfer potential <br/>Mechanism: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate <br/>ATP is formed by phosphoryl transfer from 1,3-bisphosphoglycerate <br/>Additional ATP is generated with the formation of pyruvate <br/>Two ATP molecules are formed in the conversion of glucose into pyruvate <br/>NAD+ is regenerated from the metabolism of pyruvate <br/>Fermentations provide usable energy in the absence of oxygen <br/>Fructose is converted into glycolytic intermediates by fructokinase <br/>Excessive fructose consumption can lead to pathological conditions <br/>Galactose is converted into glucose 6-phosphate <br/>Many adults are intolerant of milk because they are deficient in lactase <br/>Galactose is highly toxic if the transferase is missing <br/>16.2 The Glycolytic Pathway Is Tightly Controlled <br/>Glycolysis in muscle is regulated to meet the need for ATP <br/>The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver <br/>A family of transporters enables glucose to enter and leave animal cells <br/>Aerobic glycolysis is a property of rapidly growing cells<br/>Cancer and endurance training affect glycolysis in a similar fashion<br/>16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors <br/>Gluconeogenesis is not a reversal of glycolysis <br/>The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate<br/>Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate <br/>The conversion of fructose 1,6-bisphosphate into fructose 6-phosphate and orthophosphate is an irreversible step <br/>The generation of free glucose is an important control point<br/>Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate <br/>16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated <br/>Energy charge determines whether glycolysis or gluconeogenesis will be most active <br/>The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration <br/>Substrate cycles amplify metabolic signals and produce heat<br/>Lactate and alanine formed by contracting muscle are used by other organs <br/>Glycolysis and gluconeogenesis are evolutionarily intertwined <br/>APPENDIX Biochemistry in Focus: Triose phosphate isomerase deficiency (TPID)<br/>APPENDIX Biochemistry in Focus: Pyruvate carboxylase deficiency (PCD)<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 17 The Citric Acid Cycle<br/>17.1 The Pyruvate Dehydrogenase Complex Links Glycolysis to the Citric Acid Cycle <br/>Mechanism: The synthesis of acetyl coenzyme A from pyruvate requires three enzymes and five coenzymes <br/>Flexible linkages allow lipoamide to move between different active sites <br/>17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units <br/>Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A <br/>Mechanism: The mechanism of citrate synthase prevents undesirable reactions <br/>Citrate is isomerized into isocitrate <br/>Isocitrate is oxidized and decarboxylated to alpha-ketoglutarate <br/>Succinyl coenzyme A is formed by the oxidative decarboxylation of alpha-ketoglutarate <br/>A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A <br/>Mechanism: Succinyl coenzyme A synthetase transforms types of biochemical energy <br/>Oxaloacetate is regenerated by the oxidation of succinate <br/>The citric acid cycle produces high-transfer-potential electrons, ATP, and CO2 <br/>17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled <br/>The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation <br/>The citric acid cycle is controlled at several points<br/>Defects in the citric acid cycle contribute to the development of cancer<br/>An enzyme in lipid metabolism is hijacked to inhibit pyruvate dehydrogenase activity<br/>17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors <br/>The citric acid cycle must be capable of being rapidly replenished <br/>The disruption of pyruvate metabolism is the cause of beriberi and poisoning by mercury and arsenic <br/>The citric acid cycle may have evolved from preexisting pathways <br/>17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate<br/>APPENDIX Biochemistry in Focus: New treatments for tuberculosis may be on the horizon<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 18 Oxidative Phosphorylation<br/>18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria <br/>Mitochondria are bounded by a double membrane <br/>Mitochondria are the result of an endosymbiotic event <br/>18.2 Oxidative Phosphorylation Depends on Electron Transfer <br/>The electron-transfer potential of an electron is measured as redox potential <br/>Electron flow from NADH to molecular oxygen powers the formation of a proton gradient <br/>18.3 The Respiratory Chain Consists of Four Complexes: Three Proton Pumps and a Physical Link to the Citric Acid Cycle <br/>Iron–sulfur clusters are common components of the electron-transport chain <br/>The high-potential electrons of NADH enter the respiratory chain at NADH-Q oxidoreductase <br/>Ubiquinol is the entry point for electrons from FADH2 of flavoproteins <br/>Electrons flow from ubiquinol to cytochrome c through Q-cytochrome c oxidoreductase <br/>The Q cycle funnels electrons from a two-electron carrier to a one-electron carrier and pumps protons <br/>Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water<br/>Much of the electron-transport chain is organized into a complex called the respirasome <br/>Toxic derivatives of molecular oxygen such as superoxide radicals are scavenged by protective enzymes <br/>Electrons can be transferred between groups that are not in contact <br/>The conformation of cytochrome c has remained essentially constant for more than a billion years <br/>18.4 A Proton Gradient Powers the Synthesis of ATP <br/>ATP synthase is composed of a proton-conducting unit and a catalytic unit <br/>Proton flow through ATP synthase leads to the release of tightly bound ATP: The binding-change mechanism <br/>Rotational catalysis is the world’s smallest molecular motor <br/>Proton flow around the c ring powers ATP synthesis <br/>ATP synthase and G proteins have several common features <br/>18.5 Many Shuttles Allow Movement Across Mitochondrial Membranes <br/>Electrons from cytoplasmic NADH enter mitochondria by shuttles <br/>The entry of ADP into mitochondria is coupled to the exit of ATP by ATP-ADP translocase <br/>Mitochondrial transporters for metabolites have a common tripartite structure <br/>18.6 The Regulation of Cellular Respiration Is Governed Primarily by the Need for ATP <br/>The complete oxidation of glucose yields about 30 molecules of ATP <br/>The rate of oxidative phosphorylation is determined by the need for ATP <br/>ATP synthase can be regulated <br/>Regulated uncoupling leads to the generation of heat<br/>Reintroduction of UCP-1 into pigs may be economically valuable <br/>Oxidative phosphorylation can be inhibited at many stages <br/>Mitochondrial diseases are being discovered <br/>Mitochondria play a key role in apoptosis <br/>Power transmission by proton gradients is a central motif of bioenergetics<br/>APPENDIX Biochemistry in Focus: Leber hereditary optic neuropathy can result from defects in Complex I <br/><br/>Chapter 19 The Light Reactions of Photosynthesis<br/>19.1 Photosynthesis Takes Place in Chloroplasts <br/>The primary events of photosynthesis take place in thylakoid membranes <br/>Chloroplasts arose from an endosymbiotic event <br/>19.2 Light Absorption by Chlorophyll Induces Electron Transfer <br/>A special pair of chlorophylls initiate charge separation <br/>Cyclic electron flow reduces the cytochrome of the reaction center <br/>19.3 Two Photosystems Generate a Proton Gradient and NADPH in Oxygenic Photosynthesis <br/>Photosystem II transfers electrons from water to plastoquinone and generates a proton gradient <br/>Cytochrome bf links photosystem II to photosystem I <br/>Photosystem I uses light energy to generate reduced ferredoxin, a powerful reductant <br/>Ferredoxin–NADP+ reductase converts NADP+ into NADPH <br/>19.4 A Proton Gradient across the Thylakoid Membrane Drives ATP Synthesis <br/>The ATP synthase of chloroplasts closely resembles those of mitochondria and prokaryotes <br/>The activity of chloroplast ATP synthase is regulated <br/>Cyclic electron flow through photosystem I leads to the production of ATP instead of NADPH <br/>The absorption of eight photons yields one O2, two NADPH, and three ATP molecules <br/>19.5 Accessory Pigments Funnel Energy into Reaction Centers <br/>Resonance energy transfer allows energy to move from the site of initial absorbance to the reaction center <br/>The components of photosynthesis are highly organized <br/>Many herbicides inhibit the light reactions of photosynthesis <br/>19.6 The Ability to Convert Light into Chemical Energy Is Ancient <br/>Artificial photosynthetic systems may provide clean, renewable energy <br/>APPENDIX Biochemistry in Focus: Increasing the efficiency of photosynthesis will increase crop yields<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 20 The Calvin Cycle and the Pentose Phosphate Pathway<br/>20.1 The Calvin Cycle Synthesizes Hexoses from Carbon Dioxide and Water <br/>Carbon dioxide reacts with ribulose 1,5-bisphosphate to form two molecules of 3-phosphoglycerate <br/>Rubisco activity depends on magnesium and carbamate <br/>Rubisco activase is essential for rubisco activity <br/>Rubisco also catalyzes a wasteful oxygenase reaction: Catalytic imperfection <br/>Hexose phosphates are made from phosphoglycerate, and ribulose 1,5-bisphosphate is regenerated <br/>Three ATP and two NADPH molecules are used to bring carbon dioxide to the level of a hexose <br/>Starch and sucrose are the major carbohydrate stores in plants <br/>20.2 The Activity of the Calvin Cycle Depends on Environmental Conditions <br/>Rubisco is activated by light-driven changes in proton and magnesium ion concentrations <br/>Thioredoxin plays a key role in regulating the Calvin cycle <br/>The C4 pathway of tropical plants accelerates photosynthesis by concentrating carbon dioxide <br/>Crassulacean acid metabolism permits growth in arid ecosystems <br/>20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes Five-Carbon Sugars <br/>Two molecules of NADPH are generated in the conversion of glucose 6-phosphate into ribulose 5-phosphate <br/>The pentose phosphate pathway and glycolysis are linked by transketolase and transaldolase <br/>Mechanism: Transketolase and transaldolase stabilize carbanionic intermediates by different mechanisms<br/>20.4 The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis <br/>The rate of the oxidative phase of the pentose phosphate pathway is controlled by the level of NADP+ <br/>The flow of glucose 6-phosphate depends on the need for NADPH, ribose 5-phosphate, and ATP <br/>The pentose phosphate pathway is required for rapid cell growth <br/>Through the looking-glass: The Calvin cycle and the pentose phosphate pathway are mirror images <br/>20.5 Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species <br/>Glucose 6-phosphate dehydrogenase deficiency causes a drug-induced hemolytic anemia <br/>A deficiency of glucose 6-phosphate dehydrogenase confers an evolutionary advantage in some circumstances<br/>APPENDIX Biochemistry in Focus<br/>APPENDIX Biochemistry in Focus: Hummingbirds and the pentose phosphate pathway<br/>APPENDIX Problem-Solving Strategies<br/> <br/>Chapter 21 Glycogen Metabolism<br/>21.1 Glycogen Breakdown Requires the Interplay of Several Enzymes <br/>Phosphorylase catalyzes the phosphorolytic cleavage of glycogen to release glucose 1-phosphate <br/>Mechanism: Pyridoxal phosphate participates in the phosphorolytic cleavage of glycogen <br/>A debranching enzyme also is needed for the breakdown of glycogen <br/>Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate <br/>The liver contains glucose 6-phosphatase, a hydrolytic enzyme absent from muscle <br/>21.2 Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation <br/>Liver phosphorylase produces glucose for use by other tissues <br/>Muscle phosphorylase is regulated by the intracellular energy charge <br/>Biochemical characteristics of muscle fiber types differ <br/>Phosphorylation promotes the conversion of phosphorylase b to phosphorylase a <br/>Phosphorylase kinase is activated by phosphorylation and calcium ions<br/>An isomeric form of glycogen phosphorylase exists in the brain <br/>21.3 Epinephrine and Glucagon Signal the Need for Glycogen Breakdown <br/>G proteins transmit the signal for the initiation of glycogen breakdown <br/>Glycogen breakdown must be rapidly turned off when necessary <br/>The regulation of glycogen phosphorylase became more sophisticated as the enzyme evolved<br/>21.4 Glycogen Is Synthesized and Degraded by Different Pathways <br/>UDP-glucose is an activated form of glucose <br/>Glycogen synthase catalyzes the transfer of glucose from UDP-glucose to a growing chain <br/>A branching enzyme forms 〈-1,6 linkages <br/>Glycogen synthase is the key regulatory enzyme in glycogen synthesis <br/>Glycogen is an efficient storage form of glucose <br/>21.5 Glycogen Breakdown and Synthesis Are Reciprocally Regulated <br/>Protein phosphatase 1 reverses the regulatory effects of kinases on glycogen metabolism <br/>Insulin stimulates glycogen synthesis by inactivating glycogen synthase kinase <br/>Glycogen metabolism in the liver regulates the blood-glucose concentration <br/>A biochemical understanding of glycogen-storage diseases is possible<br/>APPENDIX Biochemistry in Focus: McArdle disease results from a lack of skeletal muscle glycogen phosphorylase<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 22 Fatty Acid Metabolism<br/>22.1 Triacylglycerols Are Highly Concentrated Energy Stores <br/>Dietary lipids are digested by pancreatic lipases <br/>Dietary lipids are transported in chylomicrons <br/>22.2 The Use of Fatty Acids as Fuel Requires Three Stages of Processing <br/>Triacylglycerols are hydrolyzed by hormone-stimulated lipases <br/>Free fatty acids and glycerol are released into the blood <br/>Fatty acids are linked to coenzyme A before they are oxidized <br/>Carnitine carries long-chain activated fatty acids into the mitochondrial matrix <br/>Acetyl CoA, NADH, and FADH2 are generated in each round of fatty acid oxidation <br/>The complete oxidation of palmitate yields 106 molecules of ATP <br/>22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation<br/>An isomerase and a reductase are required for the oxidation of unsaturated fatty acids <br/>Odd-chain fatty acids yield propionyl CoA in the final thiolysis step <br/>Vitamin B12 contains a corrin ring and a cobalt atom <br/>Mechanism: Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA <br/>Fatty acids are also oxidized in peroxisomes <br/>Some fatty acids may contribute to the development of pathological conditions <br/>22.4 Ketone Bodies Are a Fuel Source Derived from Fats<br/>Ketone bodies are a major fuel in some tissues <br/>Animals cannot convert fatty acids into glucose<br/>22.5 Fatty Acids Are Synthesized by Fatty Acid Synthase <br/>Fatty acids are synthesized and degraded by different pathways <br/>The formation of malonyl CoA is the committed step in fatty acid synthesis <br/>Intermediates in fatty acid synthesis are attached to an acyl carrier protein <br/>Fatty acid synthesis consists of a series of condensation, reduction, dehydration, and reduction reactions <br/>Fatty acids are synthesized by a multifunctional enzyme complex in animals <br/>The synthesis of palmitate requires 8 molecules of acetyl CoA, 14 molecules of NADPH, and 7 molecules of ATP <br/>Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis <br/>Several sources supply NADPH for fatty acid synthesis <br/>Fatty acid metabolism is altered in tumor cells<br/>Triacylglycerols may become an important renewable energy source <br/>22.6 The Elongation and Unsaturation of Fatty Acids are Accomplished by Accessory Enzyme Systems <br/>Membrane-bound enzymes generate unsaturated fatty acids <br/>Eicosanoid hormones are derived from polyunsaturated fatty acids <br/>Variations on a theme: Polyketide and nonribosomal peptide synthetases resemble fatty acid synthase <br/>22.7 Acetyl CoA Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism<br/>Acetyl CoA carboxylase is regulated by conditions in the cell <br/>Acetyl CoA carboxylase is regulated by a variety of hormones <br/>AMP-activated protein kinase is a key regulator of metabolism<br/>APPENDIX Biochemistry in Focus: Ethanol consumption results in triacylglycerol accumulation in the liver<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 23 Protein Turnover and Amino Acid Catabolism<br/>23.1 Proteins are Degraded to Amino Acids <br/>The digestion of dietary proteins begins in the stomach and is completed in the intestine <br/>Cellular proteins are degraded at different rates <br/>23.2 Protein Turnover Is Tightly Regulated <br/>Ubiquitin tags proteins for destruction <br/>The proteasome digests the ubiquitin-tagged proteins <br/>The ubiquitin pathway and the proteasome have prokaryotic counterparts <br/>Protein degradation can be used to regulate biological function <br/>23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen <br/>Alpha-amino groups are converted into ammonium ions by the oxidative deamination of glutamate <br/>Mechanism: Pyridoxal phosphate forms Schiff-base intermediates in aminotransferases <br/>Aspartate aminotransferase is an archetypal pyridoxal-dependent transaminase <br/>Blood levels of aminotransferases serve a diagnostic function <br/>Pyridoxal phosphate enzymes catalyze a wide array of reactions <br/>Serine and threonine can be directly deaminated <br/>Peripheral tissues transport nitrogen to the liver <br/>23.4 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates <br/>The urea cycle begins with the formation of carbamoyl phosphate <br/>Carbamoyl phosphate synthetase is the key regulatory enzyme for urea synthesis <br/>Carbamoyl phosphate reacts with ornithine to begin the urea cycle <br/>The urea cycle is linked to gluconeogenesis <br/>Urea-cycle enzymes are evolutionarily related to enzymes in other metabolic pathways <br/>Inherited defects of the urea cycle cause hyperammonemia and can lead to brain damage <br/>Urea is not the only means of disposing of excess nitrogen <br/>23.5 Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates<br/>Pyruvate is an entry point into metabolism for a number of amino acids <br/>Oxaloacetate is an entry point into metabolism for aspartate and asparagine <br/>Alpha-ketoglutarate is an entry point into metabolism for five-carbon amino acids <br/>Succinyl coenzyme A is a point of entry for several amino acids <br/>Methionine degradation requires the formation of a key methyl donor, S-adenosylmethionine<br/>Threonine deaminase initiates the degradation of threonine<br/>The branched-chain amino acids yield acetyl CoA, acetoacetate, or propionyl CoA <br/>Oxygenases are required for the degradation of aromatic amino acids<br/>Protein metabolism helps to power the flight of migratory birds <br/>23.6 Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation <br/>Phenylketonuria is one of the most common metabolic disorders <br/>Determining the basis of the neurological symptoms of phenylketonuria is an active area of research<br/>APPENDIX Biochemistry in Focus: Methylmalonic acidemia results from an inborn error of metabolism<br/>APPENDIX Problem-Solving Strategies <br/><br/>Part III SYNTHESIZING THE MOLECULES OF LIFE<br/>Chapter 24 The Biosynthesis of Amino Acids<br/>24.1 Nitrogen Fixation: Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia <br/>The iron–molybdenum cofactor of nitrogenase binds and reduces atmospheric nitrogen <br/>Ammonium ion is assimilated into an amino acid through glutamate and glutamine <br/>24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways <br/>Human beings can synthesize some amino acids but must obtain others from their diet <br/>Aspartate, alanine, and glutamate are formed by the addition of an amino group to an alpha-ketoacid <br/>A common step determines the chirality of all amino acids <br/>The formation of asparagine from aspartate requires an adenylated intermediate <br/>Glutamate is the precursor of glutamine, proline, and arginine <br/>3-Phosphoglycerate is the precursor of serine, cysteine, and glycine <br/>Tetrahydrofolate carries activated one-carbon units at several oxidation levels <br/>S-Adenosylmethionine is the major donor of methyl groups <br/>Cysteine is synthesized from serine and homocysteine <br/>High homocysteine levels correlate with vascular disease <br/>Shikimate and chorismate are intermediates in the biosynthesis of aromatic amino acids <br/>Tryptophan synthase illustrates substrate channeling in enzymatic catalysis <br/>24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis <br/>Branched pathways require sophisticated regulation <br/>The sensitivity of glutamine synthetase to allosteric regulation is altered by covalent modification <br/>24.4 Amino Acids Are Precursors of Many Biomolecules <br/>Glutathione, a gamma-glutamyl peptide, serves as a sulfhydryl buffer and an antioxidant <br/>Nitric oxide, a short-lived signal molecule, is formed from arginine<br/>Amino acids are precursors for a number of neurotransmitters <br/>Porphyrins are synthesized from glycine and succinyl coenzyme A <br/>Porphyrins accumulate in some inherited disorders of porphyrin metabolism<br/>APPENDIX Biochemistry in Focus: Tyrosine is a precursor for human pigments<br/>APPENDIX Problem-Solving Strategies <br/><br/>Chapter 25 Nucleotide Biosynthesis<br/>25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways <br/>Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation <br/>The side chain of glutamine can be hydrolyzed to generate ammonia <br/>Intermediates can move between active sites by channeling <br/>Orotate acquires a ribose ring from PRPP to form a pyrimidine nucleotide and is converted into uridylate <br/>Nucleotide mono-, di-, and triphosphates are interconvertible <br/>CTP is formed by amination of UTP <br/>Salvage pathways recycle pyrimidine bases <br/>25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways <br/>The purine ring system is assembled on ribose phosphate <br/>The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement <br/>AMP and GMP are formed from IMP <br/>Enzymes of the purine synthesis pathway associate with one another in vivo <br/>Salvage pathways economize intracellular energy expenditure <br/>25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism <br/>Mechanism: A tyrosyl radical is critical to the action of ribonucleotide reductase <br/>Stable radicals other than tyrosyl radical are employed by other ribonucleotide reductases <br/>Thymidylate is formed by the methylation of deoxyuridylate <br/>Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate, a one-carbon carrier <br/>Several valuable anticancer drugs block the synthesis of thymidylate <br/>25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition <br/>Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase <br/>The synthesis of purine nucleotides is controlled by feedback inhibition at several sites <br/>The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase <br/>25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions <br/>The loss of adenosine deaminase activity results in severe combined immunodeficiency <br/>Gout is induced by high serum levels of urate <br/>Lesch–Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme <br/>Folic acid deficiency promotes birth defects such as spina bifida<br/>APPENDIX Biochemistry in Focus: Uridine plays a role in caloric homeostasis<br/>APPENDIX Problem-Solving Strategies <br/><br/>Chapter 26 The Biosynthesis of Membrane Lipids and Steroids<br/>26.1 Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols <br/>The synthesis of phospholipids requires an activated intermediate <br/>Some phospholipids are synthesized from an activated alcohol <br/>Phosphatidylcholine is an abundant phospholipid <br/>Excess choline is implicated in the development of heart disease <br/>Base-exchange reactions can generate phospholipids <br/>Sphingolipids are synthesized from ceramide <br/>Gangliosides are carbohydrate-rich sphingolipids that contain acidic sugars <br/>Sphingolipids confer diversity on lipid structure and function <br/>Respiratory distress syndrome and Tay–Sachs disease result from the disruption of lipid metabolism <br/>Ceramide metabolism stimulates tumor growth <br/>Phosphatidic acid phosphatase is a key regulatory enzyme in lipid metabolism <br/>26.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages <br/>The synthesis of mevalonate, which is activated as isopentenyl pyrophosphate, initiates the synthesis of cholesterol <br/>Squalene (C30) is synthesized from six molecules of isopentenyl pyrophosphate (C5) <br/>Squalene cyclizes to form cholesterol <br/>26.3 The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels <br/>Lipoproteins transport cholesterol and triacylglycerols throughout the organism <br/>Low-density lipoproteins play a central role in cholesterol metabolism <br/>The absence of the LDL receptor leads to hypercholesterolemia and atherosclerosis <br/>Mutations in the LDL receptor prevent LDL release and result in receptor destruction <br/>Inability to transport cholesterol from the lysosome causes Niemann-Pick disease<br/>Cycling of the LDL receptor is regulated <br/>HDL appears to protect against atherosclerosis <br/>The clinical management of cholesterol levels can be understood at a biochemical level <br/>26.4 Important Biochemicals Are Synthesized from Cholesterol and Isoprene <br/>Letters identify the steroid rings and numbers identify the carbon atoms <br/>Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2<br/>The cytochrome P450 system is widespread and performs a protective function <br/>Pregnenolone, a precursor of many other steroids, is formed from cholesterol by cleavage of its side chain <br/>Progesterone and corticosteroids are synthesized from pregnenolone <br/>Androgens and estrogens are synthesized from pregnenolone <br/>Vitamin D is derived from cholesterol by the ring- splitting activity of light<br/>Five-carbon units are joined to form a wide variety of biomolecules<br/>Some isoprenoids have industrial applications<br/>APPENDIX Biochemistry in Focus: Excess ceramides may cause insulin insensitivity<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 27 The Integration of Metabolism<br/>27.1 Caloric Homeostasis Is a Means of Regulating Body Weight <br/>27.2 The Brain Plays a Key Role in Caloric Homeostasis <br/>Signals from the gastrointestinal tract induce feelings of satiety <br/>Leptin and insulin regulate long-term control over caloric homeostasis <br/>Leptin is one of several hormones secreted by adipose tissue <br/>Leptin resistance may be a contributing factor to obesity <br/>Dieting is used to combat obesity <br/>27.3 Diabetes Is a Common Metabolic Disease Often Resulting from Obesity <br/>Insulin initiates a complex signal-transduction pathway in muscle <br/>Metabolic syndrome often precedes type 2 diabetes <br/>Excess fatty acids in muscle modify metabolism <br/>Insulin resistance in muscle facilitates pancreatic failure <br/>Metabolic derangements in type 1 diabetes result from insulin insufficiency and glucagon excess <br/>27.4 Exercise Beneficially Alters the Biochemistry of Cells <br/>Mitochondrial biogenesis is stimulated by muscular activity <br/>Fuel choice during exercise is determined by the intensity and duration of activity <br/>27.5 Food Intake and Starvation Induce Metabolic Changes <br/>The starved–fed cycle is the physiological response to a fast <br/>Metabolic adaptations in prolonged starvation minimize protein degradation <br/>27.6 Ethanol Alters Energy Metabolism in the Liver <br/>Ethanol metabolism leads to an excess of NADH <br/>Excess ethanol consumption disrupts vitamin metabolism<br/>APPENDIX Biochemistry in Focus: Adipokines help to regulate metabolism in the liver<br/>APPENDIX Biochemistry in Focus: Exercise alters muscle and whole-body metabolism<br/>APPENDIX Problem-Solving Strategies<br/><br/>Chapter 28 Drug Development<br/>28.1 Compounds Must Meet Stringent Criteria to be Developed Into Drugs <br/>Drug must be potent and selective <br/>Drugs must have suitable properties to reach their targets <br/>Toxicity can limit drug effectiveness <br/>28.2 Drug Candidates Can Be Discovered by Serendipity, Screening, or Design <br/>Serendipitous observations can drive drug development <br/>Natural products are a valuable source of drugs and drug leads <br/>Screening libraries of synthetic compounds expands the opportunity for identification of drug leads <br/>Drugs can be designed on the basis of three-dimensional structural information about their targets <br/>28.3 Genomic Analyses Can Aid Drug Discovery <br/>Potential targets can be identified in the human proteome <br/>Animal models can be developed to test the validity of potential drug targets <br/>Potential targets can be identified in the genomes of pathogens <br/>Genetic differences influence individual responses to drugs <br/>28.4 The Clinical Development of Drugs Proceeds Through Several Phases <br/>Clinical trials are time consuming and expensive <br/>The evolution of drug resistance can limit the utility of drugs for infectious agents and cancer<br/>APPENDIX Biochemistry in Focus: Monoclonal antibodies: Expanding the drug developer’s toolbox<br/><br/>Chapter 29 DNA Replication, Repair, and Recombination<br/>29.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template <br/>DNA polymerases require a template and a primer <br/>All DNA polymerases have structural features in common <br/>Two bound metal ions participate in the polymerase reaction <br/>The specificity of replication is dictated by complementarity of shape between bases <br/>An RNA primer synthesized by primase enables DNA synthesis to begin <br/>One strand of DNA is made continuously, whereas the other strand is synthesized in fragments <br/>DNA ligase joins ends of DNA in duplex regions <br/>The separation of DNA strands requires specific helicases and ATP hydrolysis <br/>29.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases <br/>The linking number of DNA, a topological property, determines the degree of supercoiling <br/>Topoisomerases prepare the double helix for unwinding <br/>Type I topoisomerases relax supercoiled structures <br/>Type II topoisomerases can introduce negative supercoils through coupling to ATP hydrolysis <br/>29.3 DNA Replication Is Highly Coordinated <br/>DNA replication requires highly processive polymerases <br/>The leading and lagging strands are synthesized in a coordinated fashion <br/>DNA replication in Escherichia coli begins at a unique site and proceeds through initiation, elongation, and termination <br/>DNA synthesis in eukaryotes is initiated at multiple sites <br/>Telomeres are unique structures at the ends of linear chromosomes <br/>Telomeres are replicated by telomerase, a specialized polymerase that carries its own RNA template <br/>29.4 Many Types of DNA Damage Can Be Repaired <br/>Errors can arise in DNA replication <br/>Bases can be damaged by oxidizing agents, alkylating agents, and light <br/>DNA damage can be detected and repaired by a variety of systems <br/>The presence of thymine instead of uracil in DNA permits the repair of deaminated cytosine <br/>Some genetic diseases are caused by the expansion of repeats of three nucleotides <br/>Many cancers are caused by the defective repair of DNA <br/>Many potential carcinogens can be detected by their mutagenic action on bacteria <br/>29.5 DNA Recombination Plays Important Roles in Replication, Repair, and Other Processes <br/>RecA can initiate recombination by promoting strand invasion <br/>Some recombination reactions proceed through Holliday-junction intermediates<br/>APPENDIX Biochemistry in Focus: Identifying amino acids crucial for DNA replication fidelity <br/><br/>Chapter 30 RNA Synthesis and Processing <br/>30.1 RNA Polymerases Catalyze Transcription <br/>RNA chains are formed de novo and grow in the 5′-to-3′ direction <br/>RNA polymerases backtrack and correct errors <br/>RNA polymerase binds to promoter sites on the DNA template to initiate transcription <br/>Sigma subunits of RNA polymerase recognize promoter sites <br/>RNA polymerases must unwind the template double helix for transcription to take place <br/>Elongation takes place at transcription bubbles that move along the DNA template <br/>Sequences within the newly transcribed RNA signal termination <br/>Some messenger RNAs directly sense metabolite concentrations <br/>The rho protein helps to terminate the transcription of some genes <br/>Some antibiotics inhibit transcription <br/>Precursors of transfer and ribosomal RNA are cleaved and chemically modified after transcription in prokaryotes <br/>30.2 Transcription in Eukaryotes Is Highly Regulated <br/>Three types of RNA polymerase synthesize RNA in eukaryotic cells <br/>Three common elements can be found in the RNA polymerase II promoter region <br/>The TFIID protein complex initiates the assembly of the active transcription complex <br/>Multiple transcription factors interact with eukaryotic promoters <br/>Enhancer sequences can stimulate transcription at start sites thousands of bases away <br/>30.3 The Transcription Products of Eukaryotic Polymerases Are Processed <br/>RNA polymerase I produces three ribosomal RNAs <br/>RNA polymerase III produces transfer RNA <br/>The product of RNA polymerase II, the pre-mRNA transcript, acquires a 5′ cap and a 3′ poly(A) tail <br/>Small regulatory RNAs are cleaved from larger precursors <br/>RNA editing changes the proteins encoded by mRNA <br/>Sequences at the ends of introns specify splice sites in mRNA precursors <br/>Splicing consists of two sequential transesterification reactions <br/>Small nuclear RNAs in spliceosomes catalyze the splicing of mRNA precursors <br/>Transcription and processing of mRNA are coupled <br/>Mutations that affect pre-mRNA splicing cause disease <br/>Most human pre-mRNAs can be spliced in alternative ways to yield different proteins <br/>30.4 The Discovery of Catalytic RNA was Revealing in Regard to Both Mechanism and Evolution<br/>APPENDIX Biochemistry in Focus: Discovering enzymes made of RNA <br/><br/>Chapter 31 Protein Synthesis<br/>31.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences <br/>The synthesis of long proteins requires a low error frequency <br/>Transfer RNA molecules have a common design <br/>Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing <br/>31.2 Aminoacyl Transfer RNA Synthetases Read the Genetic Code <br/>Amino acids are first activated by adenylation <br/>Aminoacyl-tRNA synthetases have highly discriminating amino acid activation sites <br/>Proofreading by aminoacyl-tRNA synthetases increases the fidelity of protein synthesis <br/>Synthetases recognize various features of transfer RNA molecules <br/>Aminoacyl-tRNA synthetases can be divided into two classes <br/>31.3 The Ribosome Is the Site of Protein Synthesis <br/>Ribosomal RNAs (5S, 16S, and 23S rRNA) play a central role in protein synthesis <br/>Ribosomes have three tRNA-binding sites that bridge the 30S and 50S subunits <br/>The start signal is usually AUG preceded by several bases that pair with 16S rRNA <br/>Bacterial protein synthesis is initiated by formylmethionyl transfer RNA <br/>Formylmethionyl-tRNAf is placed in the P site of the ribosome in the formation of the 70S initiation complex <br/>Elongation factors deliver aminoacyl-tRNA to the ribosome <br/>Peptidyl transferase catalyzes peptide-bond synthesis <br/>The formation of a peptide bond is followed by the GTP-driven translocation of tRNAs and mRNA <br/>Protein synthesis is terminated by release factors that read stop codons <br/>31.4 Eukaryotic Protein Synthesis Differs from Bacterial Protein Synthesis Primarily in Translation Initiation <br/>Mutations in initiation factor 2 cause a curious pathological condition <br/>31.5 A Variety of Antibiotics and Toxins Can Inhibit Protein Synthesis <br/>Some antibiotics inhibit protein synthesis <br/>Diphtheria toxin blocks protein synthesis in eukaryotes by inhibiting translocation <br/>Some toxins modify 28S ribosomal RNA <br/>31.6 Ribosomes Bound to the Endoplasmic Reticulum Manufacture Secretory and Membrane Proteins <br/>Protein synthesis begins on ribosomes that are free in the cytoplasm <br/>Signal sequences mark proteins for translocation across the endoplasmic reticulum membrane <br/>Transport vesicles carry cargo proteins to their final destination<br/>APPENDIX Biochemistry in Focus: Selective control of gene expression by ribosomes<br/>APPENDIX Problem-Solving Strategies <br/><br/>Chapter 32 The Control of Gene Expression in Prokaryotes<br/>32.1 Many DNA-Binding Proteins Recognize Specific DNA Sequences <br/>The helix-turn-helix motif is common to many prokaryotic DNA-binding proteins <br/>32.2 Prokaryotic DNA-Binding Proteins Bind Specifically to Regulatory Sites in Operons <br/>An operon consists of regulatory elements and protein-encoding genes <br/>The lac repressor protein in the absence of lactose binds to the operator and blocks transcription <br/>Ligand binding can induce structural changes in regulatory proteins <br/>The operon is a common regulatory unit in prokaryotes <br/>Transcription can be stimulated by proteins that contact RNA polymerase <br/>32.3 Regulatory Circuits Can Result in Switching Between Patterns of Gene Expression <br/>The ⎣ repressor regulates its own expression <br/>A circuit based on the ⎣ repressor and Cro forms a genetic switch <br/>Many prokaryotic cells release chemical signals that regulate gene expression in other cells <br/>Biofilms are complex communities of prokaryotes <br/>32.4 Gene Expression Can Be Controlled at Posttranscriptional Levels <br/>Attenuation is a prokaryotic mechanism for regulating transcription through the modulation of nascent RNA secondary structure<br/>APPENDIX Biochemistry in Focus: Regulating gene expression through proteolysis <br/><br/>Chapter 33 The Control of Gene Expression in Eukaryotes<br/>33.1 Eukaryotic DNA Is Organized into Chromatin <br/>Nucleosomes are complexes of DNA and histones <br/>DNA wraps around histone octamers to form nucleosomes <br/>33.2 Transcription Factors Bind DNA and Regulate Transcription Initiation <br/>A range of DNA-binding structures are employed by eukaryotic DNA-binding proteins <br/>Activation domains interact with other proteins <br/>Multiple transcription factors interact with eukaryotic regulatory regions <br/>Enhancers can stimulate transcription in specific cell types <br/>Induced pluripotent stem cells can be generated by introducing four transcription factors into differentiated cells <br/>33.3 The Control of Gene Expression Can Require Chromatin Remodeling <br/>The methylation of DNA can alter patterns of gene expression <br/>Steroids and related hydrophobic molecules pass through membranes and bind to DNA-binding receptors <br/>Nuclear hormone receptors regulate transcription by recruiting coactivators to the transcription complex <br/>Steroid-hormone receptors are targets for drugs <br/>Chromatin structure is modulated through covalent modifications of histone tails <br/>Transcriptional repression can be achieved through histone deacetylation and other modifications <br/>33.4 Eukaryotic Gene Expression Can Be Controlled at Posttranscriptional Levels <br/>Genes associated with iron metabolism are translationally regulated in animals <br/>Small RNAs regulate the expression of many eukaryotic genes<br/>APPENDIX Biochemistry in Focus: A mechanism for consolidating epigenetic modifications <br/><br/>Part IV RESPONDING TO ENVIRONMENTAL CHANGES (Online Only)<br/>Chapter 34 Sensory Systems (Online Only)<br/>34.1 A Wide Variety of Organic Compounds Are Detected by Olfaction <br/>Olfaction is mediated by an enormous family of seven-transmembrane-helix receptors <br/>Odorants are decoded by a combinatorial mechanism <br/>34.2 Taste Is a Combination of Senses That Function by Different Mechanisms <br/>Sequencing of the human genome led to the discovery of a large family of 7TM bitter receptors<br/>A heterodimeric 7TM receptor responds to sweet compounds <br/>Umami, the taste of glutamate and aspartate, is mediated by a heterodimeric receptor related to the sweet receptor <br/>Salty tastes are detected primarily by the passage of sodium ions through channels <br/>Sour tastes arise from the effects of hydrogen ions (acids) on channels <br/>34.3 Photoreceptor Molecules in the Eye Detect Visible Light <br/>Rhodopsin, a specialized 7TM receptor, absorbs visible light <br/>Light absorption induces a specific isomerization of bound 11-cis-retinal <br/>Light-induced lowering of the calcium level coordinates recovery <br/>Color vision is mediated by three cone receptors that are homologs of rhodopsin <br/>Rearrangements in the genes for the green and red pigments lead to “color blindness”<br/>34.4 Hearing Depends on the Speedy Detection of Mechanical Stimuli <br/>Hair cells use a connected bundle of stereocilia to detect tiny motions<br/>Mechanosensory channels have been identified in Drosophila and vertebrates <br/>34.5 Touch Includes the Sensing of Pressure, Temperature, and Other Factors <br/>Studies of capsaicin reveal a receptor for sensing high temperatures and other painful stimuli<br/>APPENDIX Biochemistry in Focus: Binding many palatable tastants with a single receptor<br/><br/>Chapter 35 The Immune System (Online Only)<br/>35.1 Antibodies Possess Distinct Antigen-Binding and Effector Units <br/>35.2 Antibodies Bind Specific Molecules Through Hypervariable Loops <br/>The immunoglobulin fold consists of a beta-sandwich framework with hypervariable loops<br/>X-ray analyses have revealed how antibodies bind antigens <br/>Large antigens bind antibodies with numerous interactions <br/>35.3 Diversity Is Generated by Gene Rearrangements <br/>J (joining) genes and D (diversity) genes increase antibody diversity <br/>More than 108 antibodies can be formed by combinatorial association and somatic mutation<br/>The oligomerization of antibodies expressed on the surfaces of immature B cells triggers antibody secretion <br/>Different classes of antibodies are formed by the hopping of VH genes <br/>35.4 Major-Histocompatibility-Complex Proteins Present Peptide Antigens on Cell Surfaces for Recognition by T-Cell Receptors <br/>Peptides presented by MHC proteins occupy a deep groove flanked by alpha helices <br/>T-cell receptors are antibody-like proteins containing variable and constant regions <br/>CD8 on cytotoxic T cells acts in concert with T-cell receptors <br/>Helper T cells stimulate cells that display foreign peptides bound to class II MHC proteins <br/>Helper T cells rely on the T-cell receptor and CD4 to recognize foreign peptides on antigen-presenting cells <br/>MHC proteins are highly diverse <br/>Human immunodeficiency viruses subvert the immune system by destroying helper T cells <br/>35.5 The Immune System Contributes to the Prevention and the Development of Human Diseases <br/>T cells are subjected to positive and negative selection in the thymus <br/>Autoimmune diseases result from the generation of immune responses against self-antigens<br/>The immune system plays a role in cancer prevention <br/>Vaccines are a powerful means to prevent and eradicate disease<br/>APPENDIX Biochemistry in Focus <br/><br/>Chapter 36 Molecular Motors (Online Only)<br/>36.1 Most Molecular-Motor Proteins Are Members of the P-Loop NTPase Superfamily <br/>Molecular motors are generally oligomeric proteins with an ATPase core and an extended structure <br/>ATP binding and hydrolysis induce changes in the conformation and binding affinity of motor proteins <br/>36.2 Myosins Move Along Actin Filaments <br/>Actin is a polar, self-assembling, dynamic polymer <br/>Myosin head domains bind to actin filaments <br/>Motions of single motor proteins can be directly observed <br/>Phosphate release triggers the myosin power stroke <br/>Muscle is a complex of myosin and actin <br/>The length of the lever arm determines motor velocity <br/>36.3 Kinesin and Dynein Move Along Microtubules <br/>Microtubules are hollow cylindrical polymers <br/>Kinesin motion is highly processive <br/>36.4 A Rotary Motor Drives Bacterial Motion <br/>Bacteria swim by rotating their flagella <br/>Proton flow drives bacterial flagellar rotation <br/>Bacterial chemotaxis depends on reversal of the direction of flagellar rotation<br/> <br/>Back Matter<br/>Answers to Problems <br/>Selected Readings <br/>Index<br/><br/>Privacy Notice // Ads & Cookies // Terms of Use // Piracy // Accessibility // Code of Conduct // Site Map // Customer Support<br/>Macmillan Learning Facebook iconMacmillan Learning Twitter iconMacmillan Learning Youtube iconMacmillan Learning Linkedin iconMacmillan Learning Instagram icon |