[PDF] Biochemistry by Jeremy M. Berg John L. Tymoczko Gregory J. Gatto, Jr. Lubert Stryer 9th Jeremy M. Berg John L. Tymoczko Gregory J. Gatto, Jr. Lubert Stryer

Table of contents : About this Book Cover Page Title Page Copyright Page Dedication About the Authors Preface Molecular Evolution Clinical Applications Industrial Applications Biochemistry in Focus Acknowledgments Brief Contents Contents Chapter 1 Biochemistry: An Evolving Science 1.1 Biochemical Unity Underlies Biological Diversity 1.2 DNA Illustrates the Interplay Between Form and Function DNA is constructed from four building blocks Two single strands of DNA combine to form a double helix DNA structure explains heredity and the storage of information 1.3 Concepts from Chemistry Explain the Properties of Biological Molecules The formation of the DNA double helix as a key example The double helix can form from its component strands Covalent and noncovalent bonds are important for the structure and stability of biological molecules The double helix is an expression of the rules of chemistry The laws of thermodynamics govern the behavior of biochemical systems Heat is released in the formation of the double helix Acid?base reactions are central in many biochemical processes Acid?base reactions can disrupt the double helix Buffers regulate pH in organisms and in the laboratory 1.4 The Genomic Revolution Is Transforming Biochemistry, Medicine, and Other Fields Genome sequencing has transformed biochemistry and other fields Environmental factors influence human biochemistry Genome sequences encode proteins and patterns of expression Appendix: Visualizing Molecular Structures: Small Molecules Appendix: Functional Groups Key Terms Problems Chapter 2 Protein Composition and Structure 2.1 Proteins Are Built from a Repertoire of 20 Amino Acids 2.2 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Proteins have unique amino acid sequences specified by genes Polypeptide chains are flexible yet conformationally restricted 2.3 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds Beta sheets are stabilized by hydrogen bonding between polypeptide strands Polypeptide chains can change direction by making reverse turns and loops 2.4 Tertiary Structure: Proteins Can Fold into Globular or Fibrous Structures Fibrous proteins provide structural support for cells and tissues 2.5 Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures 2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure Amino acids have different propensities for forming ? 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 Summary Appendix: Visualizing Molecular Structures: Proteins Key Terms Problems Chapter 3 Exploring Proteins and Proteomes The proteome is the functional representation of the genome 3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function The assay: How do we recognize the protein we are looking for? Proteins must be released from the cell to be purified Proteins can be purified according to solubility, size, charge, and binding affinity Proteins can be separated by gel electrophoresis and displayed A protein purification scheme can be quantitatively evaluated Ultracentrifugation is valuable for separating biomolecules and determining their masses Protein purification can be made easier with the use of recombinant DNA technology 3.2 Immunology Provides Important Techniques with Which to Investigate Proteins Antibodies to specific proteins can be generated Monoclonal antibodies with virtually any desired specificity can be readily prepared Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay Western blotting permits the detection of proteins separated by gel electrophoresis Co-immunoprecipitation enables the identification of binding partners of a protein Fluorescent markers make the visualization of proteins in the cell possible 3.3 Mass Spectrometry Is a Powerful Technique for the Identification of Peptides and Proteins Peptides can be sequenced by mass spectrometry Proteins can be specifically cleaved into small peptides to facilitate analysis Genomic and proteomic methods are complementary The amino acid sequence of a protein provides valuable information Individual proteins can be identified by mass spectrometry 3.4 Peptides Can Be Synthesized by Automated Solid-Phase Methods 3.5 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography, NMR Spectroscopy, and Cryo-Electron Microscopy X-ray crystallography reveals three-dimensional structure in atomic detail Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution Cryo-electron microscopy is an emerging method of protein structure determination Summary Appendix: Problem-Solving Strategies Key Terms Problems Chapter 4 DNA, RNA, and the Flow of Genetic Information 4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar?Phosphate Backbone RNA and DNA differ in the sugar component and one of the bases Nucleotides are the monomeric units of nucleic acids DNA molecules are very long and have directionality 4.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure The double helix is stabilized by hydrogen bonds and van der Waals interactions DNA can assume a variety of structural forms Some DNA molecules are circular and supercoiled Single-stranded nucleic acids can adopt elaborate structures 4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information Differences in DNA density established the validity of the semiconservative replication hypothesis The double helix can be reversibly melted Unusual circular DNA exists in the eukaryotic nucleus 4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates DNA polymerase catalyzes phosphodiester-bridge formation The genes of some viruses are made of RNA 4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules Several kinds of RNA play key roles in gene expression All cellular RNA is synthesized by RNA polymerases RNA polymerases take instructions from DNA templates Transcription begins near promoter sites and ends at terminator sites Transfer RNAs are the adaptor molecules in protein synthesis 4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point Major features of the genetic code Messenger RNA contains start and stop signals for protein synthesis The genetic code is nearly universal 4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons RNA processing generates mature RNA Many exons encode protein domains Summary Appendix: Problem-Solving Strategies Key Terms Problems Chapter 5 Exploring Genes and Genomes 5.1 The Exploration of Genes Relies on Key Tools Restriction enzymes split DNA into specific fragments Restriction fragments can be separated by gel electrophoresis and visualized DNA can be sequenced by controlled termination of replication DNA probes and genes can be synthesized by automated solid-phase methods Selected DNA sequences can be greatly amplified by the polymerase chain reaction PCR is a powerful technique in medical diagnostics, forensics, and studies of molecular evolution The tools for recombinant DNA technology have been used to identify disease-causing mutations 5.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology Restriction enzymes and DNA ligase are key tools in forming recombinant DNA molecules Plasmids and ? phage are choice vectors for DNA cloning in bacteria Bacterial and yeast artificial chromosomes Specific genes can be cloned from digests of genomic DNA Complementary DNA prepared from mRNA can be expressed in host cells Proteins with new functions can be created through directed changes in DNA Recombinant methods enable the exploration of the functional effects of disease-causing mutations 5.3 Complete Genomes Have Been Sequenced and Analyzed The genomes of organisms ranging from bacteria to multicellular eukaryotes have been sequenced The sequence of the human genome has been completed Next-generation sequencing methods enable the rapid determination of a complete genome sequence Comparative genomics has become a powerful research tool 5.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision Gene-expression levels can be comprehensively examined New genes inserted into eukaryotic cells can be efficiently expressed Transgenic animals harbor and express genes introduced into their germ lines Gene disruption and genome editing provide clues to gene function and opportunities for new therapies RNA interference provides an additional tool for disrupting gene expression Tumor-inducing plasmids can be used to introduce new genes into plant cells Human gene therapy holds great promise for medicine Summary Appendix: Biochemistry in Focus Key Terms Problems Chapter 6 Exploring Evolution and Bioinformatics 6.1 Homologs Are Descended from a Common Ancestor 6.2 Statistical Analysis of Sequence Alignments Can Detect Homology The statistical significance of alignments can be estimated by shuffling Distant evolutionary relationships can be detected through the use of substitution matrices Databases can be searched to identify homologous sequences 6.3 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships Tertiary structure is more conserved than primary structure Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments Repeated motifs can be detected by aligning sequences with themselves Convergent evolution illustrates common solutions to biochemical challenges Comparison of RNA sequences can be a source of insight into RNA secondary structures 6.4 Evolutionary Trees Can Be Constructed on the Basis of Sequence Information Horizontal gene transfer events may explain unexpected branches of the evolutionary tree 6.5 Modern Techniques Make the Experimental Exploration of Evolution Possible Ancient DNA can sometimes be amplified and sequenced Molecular evolution can be examined experimentally Summary Appendix: Biochemistry in Focus Appendix: Problem-Solving Strategies Key Terms Problems Chapter 7 Hemoglobin: Portrait of a Protein in Action 7.1 Binding of Oxygen by Heme Iron Changes in heme electronic structure upon oxygen binding are the basis for functional imaging studies The structure of myoglobin prevents the release of reactive oxygen species Human hemoglobin is an assembly of four myoglobin-like subunits 7.2 Hemoglobin Binds Oxygen Cooperatively Oxygen binding markedly changes the quaternary structure of hemoglobin Hemoglobin cooperativity can be potentially explained by several models Structural changes at the heme groups are transmitted to the ?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 ?-hemoglobin chains is prevented Additional globins are encoded in the human genome Summary Appendix: Binding Models Can Be Formulated in Quantitative Terms: The Hill Plot and the Concerted Model Appendix: Biochemistry in Focus Key Terms Problems Chapter 8 Enzymes: Basic Concepts and Kinetics 8.1 Enzymes Are Powerful and Highly Specific Catalysts Many enzymes require cofactors for activity Enzymes can transform energy from one form into another 8.2 Gibbs Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes The free-energy change provides information about the spontaneity but not the rate of a reaction The standard free-energy change of a reaction is related to the equilibrium constant Enzymes alter only the reaction rate and not the reaction equilibrium 8.3 Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State The formation of an enzyme?substrate complex is the first step in enzymatic catalysis The active sites of enzymes have some common features The binding energy between enzyme and substrate is important for catalysis 8.4 The Michaelis?Menten Model Accounts for the Kinetic Properties of Many Enzymes Kinetics is the study of reaction rates The steady-state assumption facilitates a description of enzyme kinetics Variations in KM can have physiological consequences KM and Vmax values can be determined by several means KM and Vmax values are important enzyme characteristics kcat/KM is a measure of catalytic efficiency Most biochemical reactions include multiple substrates Allosteric enzymes do not obey Michaelis?Menten kinetics 8.5 Enzymes Can Be Inhibited by Specific Molecules The different types of reversible inhibitors are kinetically distinguishable Irreversible inhibitors can be used to map the active site Penicillin irreversibly inactivates a key enzyme in bacterial cell-wall synthesis Transition-state analogs are potent inhibitors of enzymes Enzymes have impact outside the laboratory or clinic 8.6 Enzymes Can Be Studied One Molecule at a Time Summary Appendix: Enzymes Are Classified on the Basis of the Types of Reactions That They Catalyze Appendix: Biochemistry in Focus Appendix: Problem-Solving Strategies Key Terms Problems Chapter 9 Catalytic Strategies A few basic catalytic principles are used by many enzymes 9.1 Proteases Facilitate a Fundamentally Difficult Reaction Chymotrypsin possesses a highly reactive serine residue Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate Serine is part of a catalytic triad that also includes histidine and aspartate Catalytic triads are found in other hydrolytic enzymes The catalytic triad has been dissected by site-directed mutagenesis Cysteine, aspartyl, and metalloproteases are other major classes of peptide-cleaving enzymes Protease inhibitors are important drugs 9.2 Carbonic Anhydrases Make a Fast Reaction Faster Carbonic anhydrase contains a bound zinc ion essential for catalytic activity Catalysis entails zinc activation of a water molecule A proton shuttle facilitates rapid regeneration of the active form of the enzyme 9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions Cleavage is by in-line displacement of 3?-oxygen from phosphorus by magnesium-activated water Restriction enzymes require magnesium for catalytic activity The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules, ensuring specificity Host-cell DNA is protected by the addition of methyl groups to specific bases Type II restriction enzymes have a catalytic core in common and are probably related by horizontal gene transfer 9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work ATP hydrolysis proceeds by the attack of water on the gamma phosphoryl group Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change The altered conformation of myosin persists for a substantial period of time Scientists can watch single molecules of myosin move Myosins are a family of enzymes containing P-loop structures Summary Appendix: Problem-Solving Strategies Key Terms Problems Chapter 10 Regulatory Strategies 10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway Allosterically regulated enzymes do not follow Michaelis?Menten kinetics ATCase consists of separable catalytic and regulatory subunits Allosteric interactions in ATCase are mediated by large changes in quaternary structure Allosteric regulators modulate the T-to-R equilibrium 10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages 10.3 Covalent Modification Is a Means of Regulating Enzyme Activity Kinases and phosphatases control the extent of protein phosphorylation Phosphorylation is a highly effective means of regulating the activities of target proteins Cyclic AMP activates protein kinase A by altering the quaternary structure Mutations in Protein Kinase A Can Cause Cushing Syndrome Exercise modifies the phosphorylation of many proteins 10.4 Many Enzymes Are Activated by Specific Proteolytic Cleavage Chymotrypsinogen is activated by specific cleavage of a single peptide bond Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site The generation of trypsin from trypsinogen leads to the activation of other zymogens Some proteolytic enzymes have specific inhibitors Serpins can be degraded by a unique enzyme Blood clotting is accomplished by a cascade of zymogen activations Prothrombin must bind to Ca2+ to be converted to thrombin Fibrinogen is converted by thrombin into a fibrin clot Vitamin K is required for the formation of ?-carboxyglutamate The clotting process must be precisely regulated Hemophilia revealed an early step in clotting Summary Appendix: Biochemistry in Focus Appendix: Problem-Solving Strategies Key Terms Problems Chapter 11 Carbohydrates 11.1 Monosaccharides Are the Simplest Carbohydrates Many common sugars exist in cyclic forms Pyranose and furanose rings can assume different conformations Glucose is a reducing sugar Monosaccharides are joined to alcohols and amines through glycosidic bonds Phosphorylated sugars are key intermediates in energy generation and biosyntheses 11.2 Monosaccharides Are Linked to Form Complex Carbohydrates Sucrose, lactose, and maltose are the common disaccharides Glycogen and starch are storage forms of glucose Cellulose, a structural component of plants, is made of chains of glucose Human milk oligosaccharides protect newborns from infection 11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins Carbohydrates can be linked to proteins through asparagine (N-linked) or through serine or threonine (O-linked) residues The glycoprotein erythropoietin is a vital hormone Glycosylation functions in nutrient sensing Proteoglycans, composed of polysaccharides and protein, have important structural roles Proteoglycans are important components of cartilage Mucins are glycoprotein components of mucus Chitin can be processed to a molecule with a variety of uses Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex Specific enzymes are responsible for oligosaccharide assembly Blood groups are based on protein glycosylation patterns Errors in glycosylation can result in pathological conditions Oligosaccharides can be ?sequenced? 11.4 Lectins Are Specific Carbohydrate-Binding Proteins Lectins promote interactions between cells and within cells Lectins are organized into different classes Influenza virus binds to sialic acid residues Summary Appendix: Biochemistry in Focus Appendix: Problem-Solving Strategies Key Terms Problems Chapter 12 Lipids and Cell Membranes Many Common Features Underlie the Diversity of Biological Membranes 12.1 Fatty Acids Are Key Constituents of Lipids Fatty acid names are based on their parent hydrocarbons Fatty acids vary in chain length and degree of unsaturation 12.2 There Are Three Common Types of Membrane Lipids Phospholipids are the major class of membrane lipids Membrane lipids can include carbohydrate moieties Cholesterol Is a Lipid Based on a Steroid Nucleus Archaeal membranes are built from ether lipids with branched chains A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety 12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media Lipid vesicles can be formed from phospholipids Lipid bilayers are highly impermeable to ions and most polar molecules 12.4 Proteins Carry Out Most Membrane Processes Proteins associate with the lipid bilayer in a variety of ways Proteins interact with membranes in a variety of ways Some proteins associate with membranes through covalently attached hydrophobic groups Transmembrane helices can be accurately predicted from amino acid sequences 12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane The fluid mosaic model allows lateral movement but not rotation through the membrane Membrane fluidity is controlled by fatty acid composition and cholesterol content Lipid rafts are highly dynamic complexes formed between cholesterol and specific lipids All biological membranes are asymmetric 12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes Summary Appendix: Biochemistry in Focus Key Terms Problems Chapter 13 Membrane Channels and Pumps The expression of transporters largely defines the metabolic activities of a given cell type 13.1 The Transport of Molecules Across a Membrane May Be Active or Passive Many molecules require protein transporters to cross membranes Free energy stored in concentration gradients can be quantified 13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes Digitalis specifically inhibits the Na+?K+ pump by blocking its dephosphorylation P-type ATPases are evolutionarily conserved and play a wide range of roles Multidrug resistance highlights a family of membrane pumps with ATP-binding cassette domains 13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another 13.4 Specific Channels Can Rapidly Transport Ions Across Membranes Action potentials are mediated by transient changes in Na+ and K+ permeability Patch-clamp conductance measurements reveal the activities of single channels The structure of a potassium ion channel is an archetype for many ion-channel structures The structure of the potassium ion channel reveals the basis of ion specificity The structure of the potassium ion channel explains its rapid rate of transport Voltage gating requires substantial conformational changes in specific ion-channel domains A channel can be inactivated by occlusion of the pore: the ball-and-chain model The acetylcholine receptor is an archetype for ligand-gated ion channels Action potentials integrate the activities of several ion channels working in concert Disruption of ion channels by mutations or chemicals can be potentially life-threatening 13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells 13.6 Specific Channels Increase the Permeability of Some Membranes to Water Summary Appendix: Biochemistry in Focus Appendix: Problem-Solving Strategies Key Terms Problems Chapter 14 Signal-Transduction Pathways Signal transduction depends on molecular circuits 14.1 Epinephrine and Angiotensin II Signaling: Heterotrimeric G Proteins Transmit Signals and Reset Themselves Ligand binding to 7TM receptors leads to the activation of heterotrimeric G proteins Activated G proteins transmit signals by binding to other proteins Cyclic AMP stimulates the phosphorylation of many target proteins by activating protein kinase A G proteins spontaneously reset themselves through GTP hydrolysis Some 7TM receptors activate the phosphoinositide cascade Calcium ion is a widely used second messenger Calcium ion often activates the regulatory protein calmodulin 14.2 Insulin Signaling: Phosphorylation Cascades Are Central to Many Signal-Transduction Processes The insulin receptor is a dimer that closes around a bound insulin molecule Insulin binding results in the cross-phosphorylation and activation of the insulin receptor The activated insulin-receptor kinase initiates a kinase cascade Insulin signaling is terminated by the action of phosphatases 14.3 EGF Signaling: Signal-Transduction Systems Are Poised to Respond EGF binding results in the dimerization of the EGF receptor The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail EGF signaling leads to the activation of Ras, a small G protein Activated Ras initiates a protein kinase cascade EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras 14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways 14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases Monoclonal antibodies can be used to inhibit signal-transduction pathways activated in tumors Protein kinase inhibitors can be effective anticancer drugs Cholera and whooping cough are the result of altered G-protein activity Summary Appendix: Biochemistry in Focus Key Terms Problems Chapter 15 Metabolism: Basic Concepts and Design 15.1 Metabolism Is Composed of Many Coupled, Interconnecting Reactions Metabolism consists of energy-yielding and energy-requiring reactions A thermodynamically unfavorable reaction can be driven by a favorable reaction 15.2 ATP Is the Universal Currency of Free Energy in Biological Systems ATP hydrolysis is exergonic ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products Phosphoryl-transfer potential is an important form of cellular energy transformation ATP may have roles other than in energy and signal transduction 15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis Phosphates play a prominent role in biochemical processes Energy from foodstuffs is extracted in three stages 15.4 Metabolic Pathways Contain Many Recurring Motifs Activated carriers exemplify the modular design and economy of metabolism Many activated carriers are derived from vitamins Key reactions are reiterated throughout metabolism Metabolic processes are regulated in three principal ways Aspects of metabolism may have evolved from an RNA world Summary Appendix: Problem-Solving Strategies Key Terms Problems Chapter 16 Glycolysis and Gluconeogenesis Glucose is generated from dietary carbohydrates Glucose is an important fuel for most organisms 16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms The enzymes of glycolysis are associated with one another Glycolysis can be divided into two parts Hexokinase traps glucose in the cell and begins glycolysis Fructose 1,6-bisphosphate is generated from glucose 6-phosphate The six-carbon sugar is cleaved into two three-carbon fragments Mechanism: Triose phosphate isomerase salvages a three-carbon fragment The oxidation of an aldehyde to an acid powers the formation of a compound with high phosphoryl-transfer potential Mechanism: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate ATP is formed by phosphoryl transfer from 1,3-bisphosphoglycerate Additional ATP is generated with the formation of pyruvate Two ATP molecules are formed in the conversion of glucose into pyruvate NAD+ is regenerated from the metabolism of pyruvate Fermentations provide usable energy in the absence of oxygen Fructose is converted into glycolytic intermediates by fructokinase Excessive fructose consumption can lead to pathological conditions Galactose is converted into glucose 6-phosphate Many adults are intolerant of milk because they are deficient in lactase Galactose is highly toxic if the transferase is missing 16.2 The Glycolytic Pathway Is Tightly Controlled Glycolysis in muscle is regulated to meet the need for ATP The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver A family of transporters enables glucose to enter and leave animal cells Aerobic glycolysis is a property of rapidly growing cells Cancer and endurance training affect glycolysis in a similar fashion 16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors Gluconeogenesis is not a reversal of glycolysis The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate The conversion of fructose 1,6-bisphosphate into fructose 6-phosphate and orthophosphate is an irreversible step The generation of free glucose is an important control point Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate 16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated Energy charge determines whether glycolysis or gluconeogenesis will be most active The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration Substrate cycles amplify metabolic signals and produce heat Lactate and alanine formed by contracting muscle are used by other organs Glycolysis and gluconeogenesis are evolutionarily intertwined Summary Appendix: Biochemistry in Focus Appendix: Biochemistry in Focus 1 Appendix: Biochemistry in Focus 2 Appendix: Problem-Solving Strategies Key Terms Problems Chapter 17 The Citric Acid Cycle The citric acid cycle harvests high-energy electrons 17.1 The Pyruvate Dehydrogenase Complex Links Glycolysis to the Citric Acid Cycle Mechanism: The synthesis of acetyl coenzyme A from pyruvate requires three enzymes and five coenzymes Flexible linkages allow lipoamide to move between different active sites 17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A Mechanism: The mechanism of citrate synthase prevents undesirable reactions Citrate is isomerized into isocitrate Isocitrate is oxidized and decarboxylated to alpha-ketoglutarate Succinyl coenzyme A is formed by the oxidative decarboxylation of alpha-ketoglutarate A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A Mechanism: Succinyl coenzyme A synthetase transforms types of biochemical energy Oxaloacetate is regenerated by the oxidation of succinate The citric acid cycle produces high-transfer-potential electrons, ATP, and CO2 17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation The citric acid cycle is controlled at several points Defects in the citric acid cycle contribute to the development of cancer An enzyme in lipid metabolism is hijacked to inhibit pyruvate dehydrogenase activity 17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors The citric acid cycle must be capable of being rapidly replenished The disruption of pyruvate metabolism is the cause of beriberi and poisoning by mercury and arsenic The citric acid cycle may have evolved from preexisting pathways 17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate Summary Appendix: Biochemistry in Focus Appendix: Biochemistry in Focus 1 Appendix: Biochemistry in Focus 2 Appendix: Problem-Solving Strategies Key Terms Problems Chapter 18 Oxidative Phosphorylation 18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria Mitochondria are bounded by a double membrane Mitochondria are the result of an endosymbiotic event 18.2 Oxidative Phosphorylation Depends on Electron Transfer The electron-transfer potential of an electron is measured as redox potential Electron flow from NADH to molecular oxygen powers the formation of a proton gradient 18.3 The Respiratory Chain Consists of Four Complexes: Three Proton Pumps and a Physical Link to the Citric Acid Cycle Iron?sulfur clusters are common components of the electron-transport chain The high-potential electrons of NADH enter the respiratory chain at NADH-Q oxidoreductase Ubiquinol is the entry point for electrons from FADH2 of flavoproteins Electrons flow from ubiquinol to cytochrome c through Q-cytochrome c oxidoreductase The Q cycle funnels electrons from a two-electron carrier to a one-electron carrier and pumps protons Cytochrome c oxidase catalyzes the reduction of molecular oxygen to wa