BIOCHEMISTRY INTERNATIONAL SEVENTH EDITIONPDF|Epub|txt|kindle电子书版本网盘下载

BIOCHEMISTRY INTERNATIONAL SEVENTH EDITIONPDF格式电子书版下载

注意：本站所有压缩包均有解压码： 点击下载压缩包解压工具

Part Ⅰ THE MOLECULAR DESIGN OF LIFE1

Chapter 1 Biochemistry：An Evolving Science1

1.1 Biochemical Unity Underlies Biological Diversity1

1.2 DNA Illustrates the Interplay Between Form and Function4

DNA is constructed from four building blocks4

Two single strands of DNA combine to form a double helix5

DNA structure explains heredity and the storage of information5

1.3 Concepts from Chemistry Explain the Properties of Biological Molecules6

The double helix can form from its component strands6

Covalent and noncovalent bonds are important for the structure and stability of biological molecules7

The double helix is an expression of the rules of chemistry10

The laws of thermodynamics govern the behavior of biochemical systems11

Heat is released in the formation of the double helix12

Acid base reactions are central in many biochemical processes13

Acid-base reactions can disrupt the double helix14

Buffers regulate pH in organisms and in the laboratory15

1.4 The Genomic Revolution Is Transforming Biochemistry and Medicine17

The sequencing of the human genome is a landmark in human history17

Genome sequences encode proteins and patterns of expression18

Individuality depends on the interplay between genes and environment19

APPENDIX：Visualizing Molecular Structures Ⅰ：Small Molecules21

Chapter 2 Protein Composition and Structure25

2.1 Proteins Are Built from a Repertoire of 20 Amino Acids27

2.2 Primary Structure：Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains33

Proteins have unique amino acid sequences specified by genes35

Polypeptide chains are flexible yet conformationally restricted36

2.3 Secondary Structure：Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix，the Beta Sheet，and Turns and Loops38

The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds38

Beta sheets are stabilized by hydrogen bonding between polypeptide strands40

Polypeptide chains can change direction by making reverse turns and loops42

Fibrous proteins provide structural support for cells and tissues43

2.4 Tertiary Structure：Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores45

2.5 Quaternary Structure：Polypeptide Chains Can Assemble into Multisubunit Structures48

2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure49

Amino acids have different propensities for forming alpha helices，beta sheets，and beta turns50

Protein folding is a highly cooperative process52

Proteins fold by progressive stabilization of intermediates rather than by random search52

Prediction of three-dimensional structure from sequence remains a great challenge54

Some proteins are inherently unstructured and can exist in multiple conformations54

Protein misfolding and aggregation are associated with some neurological diseases55

Protein modification and cleavage confer new capabilities57

APPENDIX：Visualizing Molecular Structures Ⅱ：Proteins60

Chapter 3 Exploring Proteins and Proteomes67

The proteome is the functional representation of the genome68

3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function68

The assay：How do we recognize the protein that we are looking for？69

Proteins must be released from the cell to be purified69

Proteins can be purified according to solubility，size，charge，and binding affinity70

Proteins can be separated by gel electrophoresis and displayed73

A protein purification scheme can be quantitatively evaluated77

Ultracentrifugation is valuable for separating biomolecules and determining their masses78

Protein purification can be made easier with the use of recombinant DNA technology80

3.2 Amino Acid Sequences of Proteins Can Be Determined Experimentally81

Peptide sequences can be determined by automated Edman degradation82

Proteins can be specifically cleaved into small peptides to facilitate analysis84

Genomic and proteomic methods are complementary86

3.3 Immunology Provides Important Techniques with Which to investigate Proteins86

Antibodies to specific proteins can be generated86

Monoclonal antibodies with virtually any desired specificity can be readily prepared88

Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay90

Western blotting permits the detection of proteins separated by gel electrophoresis91

Fluorescent markers make the visualization of proteins in the cell possible92

3.4 Mass Spectrometry Is a Powerful Technique for the Identification of Peptides and Proteins93

The mass of a protein can be precisely determined by mass spectrometry93

Peptides can be sequenced by mass spectrometry95

Individual proteins can be identified by mass spectrometry96

3.5 Peptides Can Be Synthesized by Automated Solid-Phase Methods97

3.6 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography and NMR Spectroscopy100

X-ray crystallography reveals three-dimensional structure in atomic detail100

Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution103

Chapter 4 DNA，RNA，and the Flow of Information113

4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar-Phosphate Backbone114

RNA and DNA differ in the sugar component and one of the bases114

Nucleotides are the monomeric units of nucleic acids115

DNA molecules are very long117

4.2 A Pair of Nucleic Acid Chains with Complementary Sequences Can Form a Double-Helical Structure117

The double helix is stabilized by hydrogen bonds and van der Waals interactions117

DNA can assume a variety of structural forms119

Z-DNA is a left-handed double helix in which backbone phosphates zigzag120

Some DNA molecules are circular and supercoiled121

Single-stranded nucleic acids can adopt elaborate structures121

4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information122

Differences in DNA density established the validity of the semiconservative-replication hypothesis123

The double helix can be reversibly melted124

4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates125

DNA polymerase catalyzes phosphodiester-bridge formation125

The genes of some viruses are made of RNA126

4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules127

Several kinds of RNA play key roles in gene expression127

All cellular RNA is synthesized by RNA polymerases128

RNA polymerases take instructions from DNA templates130

Transcription begins near promoter sites and ends at terminator sites130

Transfer RNAs are the adaptor molecules in protein synthesis131

4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point132

Major features of the genetic code133

Messenger RNA contains start and stop signals for protein synthesis134

The genetic code is nearly universal135

4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons135

RNA processing generates mature RNA136

Many exons encode protein domains137

Chapter 5 Exploring Genes and Genomes145

5.1 The Exploration of Genes Relies on Key Tools146

Restriction enzymes split DNA into specific fragments147

Restriction fragments can be separated by gel electrophoresis and visualized147

DNA can be sequenced by controlled termination of replication149

DNA probes and genes can be synthesized by automated solid-phase methods150

Selected DNA sequences can be greatly amplified by the polymerase chain reaction151

PCR is a powerful technique in medical diagnostics，forensics，and studies of molecular evolution152

The tools for recombinant DNA technology have been used to identify disease-causing mutations153

5.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology154

Restriction enzymes and DNA ligase are key tools in forming recombinant DNA molecules154

Plasmids and lambda phage are choice vectors for DNA cloning in bacteria155

Bacterial and yeast artificial chromosomes157

Specific genes can be cloned from digests of genomic DNA157

Complementary DNA prepared from mRNA can be expressed in host cells160

Proteins with new functions can be created through directed changes in DNA162

Recombinant methods enable the exploration of the functional effects of disease-causing mutations163

5.3 Complete Genomes Have Been Sequenced and Analyzed163

The genomes of organisms ranging from bacteria to multicellular eukaryotes have been sequenced164

The sequencing of the human genome has been finished165

Next-generation sequencing methods enable the rapid determination of a whole genome sequence166

Comparative genomics has become a powerful research tool166

5.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision167

Gene-expression levels can be comprehensively examined167

New genes inserted into eukaryotic cells can be efficiently expressed169

Transgenic animals harbor and express genes introduced into their germ lines170

Gene disruption provides clues to gene function170

RNA interference provides an additional tool for disrupting gene expression171

Tumor-inducing plasmids can be used to introduce new genes into plant cells172

Human gene therapy holds great promise for medicine173

Chapter 6 Exploring Evolution and Bioinformatics181

6.1 Homologs Are Descended from a Common Ancestor182

6.2 Statistical Analysis of Sequence Alignments Can Detect Homology183

The statistical significance of alignments can be estimated by shuffling185

Distant evolutionary relationships can be detected through the use of substitution matrices186

Databases can be searched to identify homologous sequences189

6.3 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships190

Tertiary structure is more conserved than primary structure191

Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments192

Repeated motifs can be detected by aligning sequences with themselves192

Convergent evolution illustrates common solutions to biochemical challenges193

Comparison of RNA sequences can be a source of insight into RNA secondary structures194

6.4 Evolutionary Trees Can Be Constructed on the Basis of Sequence Information195

6.5 Modern Techniques Make the Experimental Exploration of Evolution Possible196

Ancient DNA can sometimes be amplified and sequenced196

Molecular evolution can be examined experimentally197

Chapter 7 Hemoglobin：Portrait of a Protein in Action203

7.1 Myoglobin and Hemoglobin Bind Oxygen at Iron Atoms in Heme204

Changes in heme electronic structure upon oxygen binding are the basis for functional imaging studies205

The structure of myoglobin prevents the release of reactive oxygen species206

Human hemoglobin is an assembly of four myoglobin-like subunits207

7.2 Hemoglobin Binds Oxygen Cooperatively207

Oxygen binding markedly changes the quaternary structure of hemoglobin209

Hemoglobin cooperativity can be potentially explained by several models210

Structural changes at the heme groups are transmitted to the α1β1-α2β2 interface212

2，3-Bisphosphoglycerate in red cells is crucial in determining the oxygen affinity of hemoglobin212

Carbon monoxide can disrupt oxygen transport by hemoglobin213

7.3 Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen：The Bohr Effect214

7.4 Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease216

Sickle-cell anemia results from the aggregation of mutated deoxyhemoglobin molecules217

Thalassemia is caused by an imbalanced production of hemoglobin chains218

The accumulation of free alpha-hemoglobin chains is prevented219

Additional globins are encoded in the human genome219

APPENDIX：Binding Models Can Be Formulated in Quantitative Terms：the Hill Plot and the Concerted Model221

Chapter 8 Enzymes：Basic Concepts and Kinetics227

8.1 Enzymes Are Powerful and Highly Specific Catalysts228

Many enzymes require cofactors for activity229

Enzymes can transform energy from one form into another229

8.2 Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes230

The free-energy change provides information about the spontaneity but not the rate of a reaction230

The standard free-energy change of a reaction is related to the equilibrium constant231

Enzymes alter only the reaction rate and not the reaction equilibrium232

8.3 Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State233

The formation of an enzyme-substrate complex is the first step in enzymatic catalysis234

The active sites of enzymes have some common features235

The binding energy between enzyme and substrate is important for catalysis237

8.4 The Michaelis-Menten Equation Describes the Kinetic Properties of Many Enzymes237

Kinetics is the study of reaction rates237

The steady-state assumption facilitates a description of enzyme kinetics238

Variations in KM can have physiological consequences240

KM and Vmax values can be determined by several means240

KM and Vmax values are important enzyme characteristics241

kcat/KM is a measure of catalytic efficiency242

Most biochemical reactions include multiple substrates243

Allosteric enzymes do not obey Michaelis-Menten kinetics245

8.5 Enzymes Can Be Inhibited by Specific Molecules246

Reversible inhibitors are kinetically distinguishable247

Irreversible inhibitors can be used to map the active site249

Transition-state analogs are potent inhibitors of enzymes251

Catalytic antibodies demonstrate the importance of selective binding of the transition state to enzymatic activity251

Penicillin irreversibly inactivates a key enzyme in bacterial cell-wall synthesis252

8.6 Enzymes Can Be Studied One Molecule at a Time254

APPENDIX：Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze256

Chapter 9 Catalytic Strategies261

A few basic catalytic principles are used by many enzymes262

9.1 Proteases Facilitate a Fundamentally Difficult Reaction263

Chymotrypsin possesses a highly reactive serine residue263

Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate264

Serine is part of a catalytic triad that also includes histidine and aspartate265

Catalytic triads are found in other hydrolytic enzymes268

The catalytic triad has been dissected by site-directed mutagenesis270

Cysteine，aspartyl，and metalloproteases are other major classes of peptide-cleaving enzymes271

Protease inhibitors are important drugs272

9.2 Carbonic Anhydrases Make a Fast Reaction Faster274

Carbonic anhydrase contains a bound zinc ion essential for catalytic activity275

Catalysis entails zinc activation of a water molecule276

A proton shuttle facilitates rapid regeneration of the active form of the enzyme277

Convergent evolution has generated zinc-based active sites in different carbonic anhydrases279

9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions279

Cleavage is by in-line displacement of 3’-oxygen from phosphorus by magnesium-activated water280

Restriction enzymes require magnesium for catalytic activity282

The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules，ensuring specificity283

Host-cell DNA is protected by the addition of methyl groups to specific bases285

Type Ⅱ restriction enzymes have a catalytic core in common and are probably related by horizontal gene transfer286

9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work287

ATP hydrolysis proceeds by the attack of water on the gamma-phosphoryl group287

Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change288

The altered conformation of myosin persists for a substantial period of time290

Myosins are a family of enzymes containing P-loop structures291

Chapter 10 Regulatory Strategies299

10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway300

Allosterically regulated enzymes do not follow Michaelis-Menten kinetics301

ATCase consists of separable catalytic and regulatory subunits301

Allosteric interactions in ATCase are mediated by large changes in quaternary structure302

Allosteric regulators modulate the T-to-R equilibrium305

10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages306

10.3 Covalent Modification Is a Means of Regulating Enzyme Activity307

Kinases and phosphatases control the extent of protein phosphorylation308

Phosphorylation is a highly effective means of regulating the activities of target proteins310

Cyclic AMP activates protein kinase A by altering the quaternary structure311

ATP and the target protein bind to a deep cleft in the catalytic subunit of protein kinase A312

10.4 Many Enzymes Are Activated by Specific Proteolytic Cleavage312

Chymotrypsinogen is activated by specific cleavage of a single peptide bond313

Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site314

The generation of trypsin from trypsinogen leads to the activation of other zymogens315

Some proteolytic enzymes have specific inhibitors316

Blood clotting is accomplished by a cascade of zymogen activations317

Fibrinogen is converted by thrombin into a fibrin clot318

Prothrombin is readied for activation by a vitamin K-dependent modification320

Hemophilia revealed an early step in clotting321

The clotting process must be precisely regulated321

Chapter 11 Carbohydrates329

11.1 Monosaccharides Are the Simplest Carbohydrates330

Many common sugars exist in cyclic forms332

Pyranose and furanose rings can assume different conformations334

Glucose is a reducing sugar335

Monosaccharides are joined to alcohols and amines through glycosidic bonds336

Phosphorylated sugars are key intermediates in energy generation and biosyntheses336

11.2 Monosaccharides Are Linked to Form Complex Carbohydrates337

Sucrose，lactose，and maltose are the common disaccharides337

Glycogen and starch are storage forms of glucose338

Cellulose，a structural component of plants，is made of chains of glucose338

11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins339

Carbohydrates can be linked to proteins through asparagine（N-linked）or through serine or threonine（O-linked）residues340

The glycoprotein erythropoietin is a vital hormone340

Proteoglycans，composed of polysaccharides and protein，have important structural roles341

Proteoglycans are important components of cartilage342

Mucins are glycoprotein components of mucus343

Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex343

Specific enzymes are responsible for oligosaccharide assembly345

Blood groups are based on protein glycosylation patterns345

Errors in glycosylation can result in pathological conditions346

Oligosaccharides can be “sequenced”346

11.4 Lectins Are Specific Carbohydrate-Binding Proteins347

Lectins promote interactions between cells348

Lectins are organized into different classes348

Influenza virus binds to sialic acid residues349

Chapter 12 Lipids and Cell Membranes357

Many common features underlie the diversity of biological membranes358

12.1 Fatty Acids Are Key Constituents of Lipids358

Fatty acid names are based on their parent hydrocarbons358

Fatty acids vary in chain length and degree of unsaturation359

12.2 There Are Three Common Types of Membrane Lipids360

Phospholipids are the major class of membrane lipids360

Membrane lipids can include carbohydrate moieties361

Cholesterol is a lipid based on a steroid nucleus362

Archaeal membranes are built from ether lipids with branched chains362

A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety363

12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media364

Lipid vesicles can be formed from phospholipids365

Lipid bilayers are highly impermeable to ions and most polar molecules366

12.4 Proteins Carry Out Most Membrane Processes367

Proteins associate with the lipid bilayer in a variety of ways367

Proteins interact with membranes in a variety of ways368

Some proteins associate with membranes through covalently attached hydrophobic groups371

Transmembrane helices can be accurately predicted from amino acid sequences371

12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane373

The fluid mosaic model allows lateral movement but not rotation through the membrane374

Membrane fluidity is controlled by fatty acid composition and cholesterol content374

Lipid rafts are highly dynamic complexes formed between cholesterol and specific lipids375

All biological membranes are asymmetric375

12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes376

Chapter 13 Membrane Channels and Pumps383

The expression of transporters largely defines the metabolic activities of a given cell type384

13.1 The Transport of Molecules Across a Membrane May Be Active or Passive384

Many molecules require protein transporters to cross membranes384

Free energy stored in concentration gradients can be quantified385

13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes386

P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes386

Digitalis specifically inhibits the Na＋-K＋pump by blocking its dephosphorylation389

P-type ATPases are evolutionarily conserved and play a wide range of roles390

Multidrug resistance highlights a family of membrane pumps with ATP-binding cassette domains390

13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another392

13.4 Specific Channels Can Rapidly Transport Ions Across Membranes394

Action potentials are mediated by transient changes in Na＋and K＋permeability394

Patch-clamp conductance measurements reveal the activities of single channels395

The structure of a potassium ion channel is an archetype for many ion-channel structures395

The structure of the potassium ion channel reveals the basis of ion specificity396

The structure of the potassium ion channel explains its rapid rate of transport399

Voltage gating requires substantial conformational changes in specific ion-channel domains399

A channel can be activated by occlusion of the pore：the ball-and-chain model400

The acetylcholine receptor is an archetype for ligand-gated ion channels401

Action potentials integrate the activities of several ion channels working in concert402

Disruption of ion channels by mutations or chemicals can be potentially life threatening404

13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells405

13.6 Specific Channels Increase the Permeability of Some Membranes to Water406

Chapter 14 Signal-Transduction Pathways415

Signal transduction depends on molecular circuits416

14.1 Heterotrimeric G Proteins Transmit Signals and Reset Themselves417

Ligand binding to 7TM receptors leads to the activation of heterotrimeric G proteins419

Activated G proteins transmit signals by binding to other proteins420

Cyclic AMP stimulates the phosphorylation of many target proteins by activating protein kinase A420

G proteins spontaneously reset themselves through GTP hydrolysis421

Some 7TM receptors activate the phosphoinositide cascade422

Calcium ion is a widely used second messenger423

Calcium ion often activates the regulatory protein calmodulin424

14.2 Insulin Signaling：Phosphorylation Cascades Are Central to Many Signal-Transduction Processes425

The insulin receptor is a dimer that closes around a bound insulin molecule426

Insulin binding results in the cross-phosphorylation and activation of the insulin receptor426

The activated insulin-receptor kinase initiates a kinase cascade426

Insulin signaling is terminated by the action of phosphatases429

14.3 EGF Signaling：Signal-Transduction Pathways Are Poised to Respond429

EGF binding results in the dimerization of the eGF receptor429

The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail431

EGF signaling leads to the activation of Ras，a small G protein431

Activated Ras initiates a protein kinase cascade432

EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras432

14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways433

14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases434

Monoclonal antibodies can be used to inhibit signal-transduction pathways activated in tumors434

Protein kinase inhibitors can be effective anticancer drugs435

Cholera and whooping cough are due to altered G-protein activity435

Part Ⅱ TRANSDUCING AND STORING ENERGY443

Chapter 15 Metabolism：Basic Concepts and Design443

15.1 Metabolism Is Composed of Many Coupled，Interconnecting Reactions444

Metabolism consists of energy-yielding and energy-requiring reactions444

A thermodynamically unfavorable reaction can be driven by a favorable reaction445

15.2 ATP Is the Universal Currency of Free Energy in Biological Systems446

ATP hydrolysis is exergonic446

ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions447

The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products449

Phosphoryl-transfer potential is an important form of cellular energy transformation450

15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy451

Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis452

Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis453

Energy from foodstuffs is extracted in three stages453

15.4 Metabolic Pathways Contain Many Recurring Motifs454

Activated carriers exemplify the modular design and economy of metabolism454

Many activated carriers are derived from vitamins457

Key reactions are reiterated throughout metabolism459

Metabolic processes are regulated in three principal ways461

Aspects of metabolism may have evolved from an RNA world463

Chapter 16 Glycolysis and Gluconeogenesis469

Glucose is generated from dietary carbohydrates470

Glucose is an important fuel for most organisms471

16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms471

Hexokinase traps glucose in the cell and begins glycolysis471

Fructose 1，6-bisphosphate is generated from glucose 6-phosphate473

The six-carbon sugar is cleaved into two three-carbon fragments474

Mechanism：Triose phosphate isomerase salvages a three-carbon fragment475

The oxidation of an aldehyde to an acid powers the formation of a compound with high phosphoryl-transfer potential476

Mechanism：Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate478

ATP is formed by phosphoryl transfer from 1，3-bisphosphoglycerate479

Additional ATP is generated with the formation of pyruvate480

Two ATP molecules are formed in the conversion of glucose into pyruvate481

NAD＋is regenerated from the metabolism of pyruvate482

Fermentations provide usable energy in the absence of oxygen484

The binding site for NAD＋is similar in many dehydrogenases485

Fructose and galactose are converted into glycolytic intermediates485

Many adults are intolerant of milk because they are deficient in lactase487

Galactose is highly toxic if the transferase is missing488

16.2 The Glycolytic Pathway Is Tightly Controlled488

Glycolysis in muscle is regulated to meet the need for ATP489

The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver490

A family of transporters enables glucose to enter and leave animal cells493

Cancer and exercise training affect glycolysis in a similar fashion494

16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors495

Gluconeogenesis is not a reversal of glycolysis497

The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate498

Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate499

The conversion of fructose 1，6-bisphosphate into fructose 6-phosphate and orthophosphate is an irreversible step500

The generation of free glucose is an important control point500

Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate501

16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated502

Energy charge determines whether glycolysis or gluconeogenesis will be most active502

The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration503

Substrate cycles amplify metabolic signals and produce heat505

Lactate and alanine formed by contracting muscle are used by other organs505

Glycolysis and gluconeogenesis are evolutionarily intertwined507

Chapter 17 The Citric Acid Cycle515

The citric acid cycle harvests high-energy electrons516

17.1 Pyruvate Dehydrogenase Links Glycolysis to the Citric Acid Cycle517

Mechanism：The synthesis of acetyl coenzyme a frompyruvate requires three enzymes and five coenzymes518

Flexible linkages allow lipoamide to move between different active sites520

17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units521

Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A522

Mechanism：The mechanism of citrate synthase prevents undesirable reactions522

Citrate is isomerized into isocitrate524

Isocitrate is oxidized and decarboxylated to alpha-ketoglutarate524

Succinyl coenzyme A is formed by the oxidative decarboxylation of alpha-ketoglutarate525

A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A525

Mechanism：Succinyl coenzyme A synthetase transforms types of biochemical energy526

Oxaloacetate is regenerated by the oxidation of succinate527

The citric acid cycle produces high-transfer-potential electrons，ATP，and CO2528

17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled530

The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation531

The citric acid cycle is controlled at several points532

Defects in the citric acid cycle contribute to the development of cancer533

17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors534

The citric acid cycle must be capable of being rapidly replenished534

The disruption of pyruvate metabolism is the cause of beriberi and poisoning by mercury and arsenic535

The citric acid cycle may have evolved from preexisting pathways536

17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate536

Chapter 18 Oxidative Phosphorylation543

18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria544

Mitochondria are bounded by a double membrane544

Mitochondria are the result of an endosymbiotic event545

18.2 Oxidative Phosphorylation Depends on Electron Transfer546

The electron-transfer potential of an electron is measured as redox potential546

A 1.14-volt potential difference between NADH and molecular oxygen drives electron transport through the chain and favors the formation of a proton gradient548

18.3 The Respiratory Chain Consists of Four Complexes：Three Proton Pumps and a Physical Link to the Citric Acid Cycle549

The high-potential electrons of NADH enter the respiratory chain at NADH-Qoxidoreductase551

Ubiquinol is the entry point for electrons from FADH2 of flavoproteins553

Electrons flow from ubiquinol to cytochrome c through Q-cytochrome c oxidoreductase553

The Qcycle funnels electrons from a two-electron carrier to a one-electron carrier and pumps protons554

Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water555

Toxic derivatives of molecular oxygen such as superoxide radical are scavenged by protective enzymes558

Electrons can be transferred between groups that are not in contact560

The conformation of cytochrome c has remained essentially constant for more than a billion years561

18.4 A Proton Gradient Powers the Synthesis of ATP561

ATP synthase is composed of a proton-conducting unit and a catalytic unit563

Proton flow through ATP synthase leads to the release of tightly bound ATP：The binding-change mechanism564

Rotational catalysis is the world’s smallest molecular motor565

Proton flow around the c ring powers ATP synthesis566

ATP synthase and G proteins have several common features568

18.5 Many Shuttles Allow Movement Across Mitochondrial Membranes568

Electrons from cytoplasmic NADH enter mitochondria by shuttles569

The entry of ADP into mitochondria is coupled to the exit of ATP by ATP-ADP translocase570

Mitochondrial transporters for metabolites have a common tripartite structure571

18.6 The Regulation of Cellular Respiration Is Governed Primarily by the Need for ATP572

The complete oxidation of glucose yields about 30 molecules of ATP572

The rate of oxidative phosphorylation is determined by the need for ATP573

Regulated uncoupling leads to the generation of heat574

Oxidative phosphorylation can be inhibited at many stages576

Mitochondrial diseases are being discovered576

Mitochondria play a key role in apoptosis577

Power transmission by proton gradients is a central motif of bioenergetics577

Chapter 19 The Light Reactions of Photosynthesis585

Photosynthesis converts light energy into chemical energy586

19.1 Photosynthesis Takes Place in Chloroplasts587

The primary events of photosynthesis take place in thylakoid membranes587

Chloroplasts arose from an endosymbiotic event588

19.2 Light Absorption by Chlorophyll Induces Electron Transfer588

A special pair of chlorophylls initiate charge separation589

Cyclic electron flow reduces the cytochrome of the reaction center592

19.3 Two Photosystems Generate a Proton Gradient and NADPH in Oxygenic Photosynthesis592

Photosystem Ⅱ transfers electrons from water to plastoquinone and generates a proton gradient592

Cytochrome bf links photosystem Ⅱ to photosystem Ⅰ595

Photosystem I uses light energy to generate reduced ferredoxin，a powerful reductant595

Ferredoxin-NADP＋reductase converts NADP＋into NADPH596

19.4 A Proton Gradient Across the Thylakoid Membrane Drives ATP Synthesis597

The ATP synthase of chloroplasts closely resembles those of mitochondria and prokaryotes598

Cyclic electron flow through photosystem I leads to the production of ATP instead of NADPH599

The absorption of eight photons yields one O2，two NADPH，and three ATP molecules600

19.5 Accessory Pigments Funnel Energy into Reaction Centers601

Resonance energy transfer allows energy to move from the site of initial absorbance to the reaction center601

Light-harvesting complexes contain additional chlorophylls and carotinoids602

The components of photosynthesis are highly organized603

Many herbicides inhibit the light reactions of photosynthesis604

19.6 The Ability to Convert Light into Chemical Energy Is Ancient604

Chapter 20 The Calvin Cycle and Pentose Phosphate Pathway609

20.1 The Calvin Cycle Synthesizes Hexoses from Carbon Dioxide and Water610

Carbon dioxide reacts with ribulose 1，5-bisphosphate to form two molecules of 3-phosphoglycerate611

Rubisco activity depends on magnesium and carbamate612

Rubisco also catalyzes a wasteful oxygenase reaction：Catalytic imperfection613

Hexose phosphates are made from phosphoglycerate，and ribulose 1，5-bisphosphate is regenerated614

Three ATP and two NADPH molecules are used to bring carbon dioxide to the level of a hexose617

Starch and sucrose are the major carbohydrate stores in plants617

20.2 The Activity of the Calvin Cycle Depends on Environmental Conditions617

Rubisco is activated by light-driven changes in proton and magnesium ion concentrations618

Thioredoxin plays a key role in regulating the Calvin cycle618

The C4 pathway of tropical plants accelerates photosynthesis by concentrating carbon dioxide619

Crassulacean acid metabolism permits growth in arid ecosystems620

20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes Five-Carbon Sugars621

Two molecules of NADPH are generated in the conversion of glucose 6-phosphate into ribulose 5-phosphate621

The pentose phosphate pathway and glycolysis are linked by transketolase and transaldolase621

Mechanism：Transketolase and transaldolase stabilize carbanionic intermediates by different mechanisms624

20.4 The Metabolism of Glucose 6-phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis626

The rate of the pentose phosphate pathway is controlled by the level of NADP＋626

The flow of glucose 6-phosphate depends on the need for NADPH，ribose 5-phosphate，and ATP627

Through the looking-glass：The Calvin cycle and the pentose phosphate pathway are mirror images629

20.5 Glucose 6-phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species629

Glucose 6-phosphate dehydrogenase deficiency causes a drug-induced hemolytic anemia629

A deficiency of glucose 6-phosphate dehydrogenase confers an evolutionary advantage in some circumstances631

Chapter 21 Glycogen Metabolism637

Glycogen metabolism is the regulated release and storage of glucose638

21.1 Glycogen Breakdown Requires the Interplay of Several Enzymes639

Phosphorylase catalyzes the phosphorolytic cleavage of glycogen to release glucose 1-phosphate639

Mechanism：Pyridoxal phosphate participates in the phosphorolytic cleavage of glycogen640

A debranching enzyme also is needed for the breakdown of glycogen641

Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate642

The liver contains glucose 6-phosphatase，a hydrolytic enzyme absent from muscle643

21.2 Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation643

Muscle phosphorylase is regulated by the intracellular energy charge643

Liver phosphorylase produces glucose for use by other tissues645

Phosphorylase kinase is activated by phosphorylation and calcium ions645

21.3 Epinephrine and Glucagon Signal the Need for Glycogen Breakdown646

G proteins transmit the signal for the initiation of glycogen breakdown646

Glycogen breakdown must be rapidly turned off when necessary648

The regulation of glycogen phosphorylase became more sophisticated as the enzyme evolved649

21.4 Glycogen Is Synthesized and Degraded by Different Pathways649

UDP-glucose is an activated form of glucose649

Glycogen synthase catalyzes the transfer of glucose from UDP-glucose to a growing chain650

A branching enzyme forms α-1，6 linkages651

Glycogen synthase is the key regulatory enzyme in glycogen synthesis651

Glycogen is an efficient storage form of glucose651

21.5 Glycogen Breakdown and Synthesis Are Reciprocally Regulated652

Protein phosphatase 1 reverses the regulatory effects of kinases on glycogen metabolism653

Insulin stimulates glycogen synthesis by inactivating glycogen synthase kinase654

Glycogen metabolism in the liver regulates the blood-glucose level655

A biochemical understanding of glycogen-storage diseases is possible656

Chapter 22 Fatty Acid Metabolism663

Fatty acid degradation and synthesis mirror each other in their chemical reactions664

22.1 Triacylglycerols Are Highly Concentrated Energy Stores665

Dietary lipids are digested by pancreatic lipases665

Dietary lipids are transported in chylomicrons666

22.2 The Use of Fatty Acids As Fuel Requires Three Stages of Processing667

Triacylglycerols are hydrolyzed by hormone-stimulated lipases667

Fatty acids are linked to coenzyme A before they are oxidized668

Carnitine carries long-chain activated fatty acids into the mitochondrial matrix669

Acetyl CoA，NADH，and FADH2 are generated in each round of fatty acid oxidation670

The complete oxidation of palmitate yields 106 molecules of ATP671

22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation672

An isomerase and a reductase are required for the oxidation of unsaturated fatty acids672

Odd-chain fatty acids yield propionyl CoA in the final thiolysis step673

Vitamin B12 contains a corrin ring and a cobalt atom674

Mechanism：Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA675

Fatty acids are also oxidized in peroxisomes676

Ketone bodies are formed from acetyl CoA when fat breakdown predominates677

Ketone bodies are a major fuel in some tissues678

Animals cannot convert fatty acids into glucose680

22.4 Fatty Acids Are Synthesized by Fatty Acid Synthase680

Fatty acids are synthesized and degraded by different pathways680

The formation of malonyl CoA is the committed step in fatty acid synthesis681

Intermediates in fatty acid synthesis are attached to an acyl carrier protein681

Fatty acid synthesis consists of a series of condensation，reduction，dehydration，and reduction reactions682

Fatty acids are synthesized by a multifunctional enzyme complex in animals683

The synthesis of palmitate requires 8 molecules of acetyl CoA，14 molecules of NADPH，and 7 molecules of ATP685

Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis686

Several sources supply NADPH for fatty acid synthesis686

Fatty acid synthase inhibitors may be useful drugs687

22.5 The Elongation and Unsaturation of Fatty Acids Are Accomplished by Accessory Enzyme Systems687

Membrane-bound enzymes generate unsaturated fatty acids688

Eicosanoid hormones are derived from polyunsaturated fatty acids688

22.6 Acetyl CoA Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism690

Acetyl CoA carboxylase is regulated by conditions in the cell690

Acetyl CoA carboxylase is regulated by a variety of hormones690

Chapter 23 Protein Turnover and Amino Acid Catabolism697

23.1 Proteins Are Degraded to Amino Acids698

The digestion of dietary proteins begins in the stomach and is completed in the intestine698

Cellular proteins are degraded at different rates699

23.2 Protein Turnover Is Tightly Regulated699

Ubiquitin tags proteins for destruction699

The proteasome digests the ubiquitin-tagged proteins701

The ubiquitin pathway and the proteasome have prokaryotic counterparts701

Protein degradation can be used to regulate biological function702

23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen704

Alpha-amino groups are converted into ammonium ions by the oxidative deamination of glutamate704

Mechanism：Pyridoxal phosphate forms Schiff-base intermediates in aminotransferases705

Aspartate aminotransferase is an archetypal pyridoxal-dependent transaminase706

Pyridoxal phosphate enzymes catalyze a wide array of reactions707

Serine and threonine can be directly deaminated708

Peripheral tissues transport nitrogen to the liver708

23.4 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates709

The urea cycle begins with the formation of carbamoyl phosphate709

The urea cycle is linked to gluconeogenesis711

Urea-cycle enzymes are evolutionarily related to enzymes in other metabolic pathways712

Inherited defects of the urea cycle cause hyperammonemia and can lead to brain damage712

Urea is not the only means of disposing of excess nitrogen713

23.5 Carbon Atoms of Degraded Amino Acids Emerge As Major Metabolic Intermediates714

Pyruvate is an entry point into metabolism for a number of amino acids715

Oxaloacetate is an entry point into metabolism for aspartate and asparagine716

Alpha-ketoglutarate is an entry point into metabolism for five-carbon amino acids716

Succinyl coenzyme A is a point of entry for several nonpolar amino acids717

Methionine degradation requires the formation of a key methyl donor，S-adenosylmethionine717

The branched-chain amino acids yield acetyl CoA，acetoacetate，or propionyl CoA717

Oxygenases are required for the degradation of aromatic amino acids719

23.6 Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation721

Part Ⅲ SYNTHESIZING THE MOLECULES OF LIFE729

Chapter 24 The Biosynthesis of Amino Acids729

Amino acid synthesis requires solutions to three key biochemical problems730

24.1 Nitrogen Fixation：Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia730

The iron-molybdenum cofactor of nitrogenase binds and reduces atmospheric nitrogen731

Ammonium ion is assimilated into an amino acid through glutamate and glutamine733

24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways735

Human beings can synthesize some amino acids but must obtain others from the diet735

Aspartate，alanine，and glutamate are formed by the addition of an amino group to an alpha-ketoacid736

A common step determines the chirality of all amino acids737

The formation of asparagine from aspartate requires an adenylated intermediate737

Glutamate is the precursor of glutamine，proline，and arginine738

3-Phosphoglycerate is the precursor of serine，cysteine，and glycine738

Tetrahydrofolate carries activated one-carbon units at several oxidation levels739

S-Adenosylmethionine is the major donor of methyl groups740

Cysteine is synthesized from serine and homocysteine742

High homocysteine levels correlate with vascular disease743

Shikimate and chorismate are intermediates in the biosynthesis of aromatic amino acids743

Tryptophan synthase illustrates substrate channeling in enzymatic catalysis746

24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis747

Branched pathways require sophisticated regulation747

An enzymatic cascade modulates the activity of glutamine synthetase749

24.4 Amino Acids Are Precursors of Many Biomolecules750

Glutathione，a gamma-glutamyl peptide，serves as a sulfhydryl buffer and an antioxidant751

Nitric oxide，a short-lived signal molecule，is formed from arginine751

Porphyrins are synthesized from glycine and succinyl coenzyme A752

Porphyrins accumulate in some inherited disorders of porphyrin metabolism754

Chapter 25 Nucleotide Biosynthesis761

Nucleotides can be synthesized by de novo or salvage pathways762

25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways763

Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation763

The side chain of glutamine can be hydrolyzed to generate ammonia763

Intermediates can move between active sites by channeling763

Orotate acquires a ribose ring from PRPP to form a pyrimidine nucleotide and is converted into uridylate764

Nucleotide mono-，di-，and triphosphates are interconvertible765

CTP is formed by amination of UTP765

Salvage pathways recycle pyrimidine bases766

25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways766

The purine ring system is assembled on ribose phosphate766

The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement767

AMP and GMP are formed from IMP769

Enzymes of the purine synthesis pathway associate with one another in vivo770

Salvage pathways economize intracellular energy expenditure770

25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism771

Mechanism：A tyrosyl radical is critical to the action of ribonucleotide reductase771

Stable radicals other than tyrosyl radical are employed by other ribonucleotide reductases773

Thymidylate is formed by the methylation of deoxyuridylate774

Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate，a one-carbon carrier775

Several valuable anticancer drugs block the synthesis of thymidylate775

25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition776

Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase777

The synthesis of purine nucleotides is controlled by feedback inhibition at several sites777

The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase778

25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions778

The loss of adenosine deaminase activity results in severe combined immunodeficiency778

Gout is induced by high serum levels of urate779

Lesch-Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme780

Folic acid deficiency promotes birth defects such as spina bifida781

Chapter 26 The Biosynthesis of Membrane Lipids and Steroids787

26.1 Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols788

The synthesis of phospholipids requires an activated intermediate789

Sphingolipids are synthesized from ceramide791

Gangliosides are carbohydrate-rich sphingolipids that contain acidic sugars792

Sphingolipids confer diversity on lipid structure and function793

Respiratory distress syndrome and Tay-Sachs disease result from the disruption of lipid metabolism793

Phosphatiditic acid phosphatase is a key regulatory enzyme in lipid metabolism794

26.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages795

The synthesis of mevalonate，which is activated as isopentenyl pyrophosphate，initiates the synthesis of cholesterol795

Squalene（C30）is synthesized from six molecules of isopentenyl pyrophosphate（C5）796

Squalene cyclizes to form cholesterol797

26.3 The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels798

Lipoproteins transport cholesterol and triacylglycerols throughout the organism801

The blood levels of certain lipoproteins can serve diagnostic purposes802

Low-density lipoproteins play a central role in cholesterol metabolism803

The absence of the LDL receptor leads to hypercholesterolemia and atherosclerosis804

Mutations in the LDL receptor prevent LDL release and result in receptor destruction805

HDL appears to protect against arteriosclerosis806

The clinical management of cholesterol levels can be understood at a biochemical level807

26.4 Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones807

Letters identify the steroid rings and numbers identify the carbon atoms809

Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2809

The cytochrome P450 system is widespread and performs a protective function810

Pregnenolone，a precursor of many other steroids，is formed from cholesterol by cleavage of its side chain811

Progesterone and corticosteroids are synthesized from pregnenolone811

Androgens and estrogens are synthesized from pregnenolone812

Vitamin D is derived from cholesterol by the ring-splitting activity of light813

Chapter 27 The Integration of Metabolism821

27.1 Caloric Homeostasis Is a Means of Regulating Body Weight822

27.2 The Brain Plays a Key Role in Caloric Homeostasis824

Signals from the gastrointestinal tract induce feelings of satiety824

Leptin and insulin regulate long-term control over caloric homeostasis825

Leptin is one of several hormones secreted by adipose tissue826

Leptin resistance may be a contributing factor to obesity827

Dieting is used to combat obesity827

27.3 Diabetes Is a Common Metabolic Disease Often Resulting from Obesity828

Insulin initiates a complex signal-transduction pathway in muscle828

Metabolic syndrome often precedes type 2 diabetes830

Excess fatty acids in muscle modify metabolism830

Insulin resistance in muscle facilitates pancreatic failure831

Metabolic derangements in type 1 diabetes result from insulin insufficiency and glucagon excess832

27.4 Exercise Beneficially Alters the Biochemistry of Cells833

Mitochondrial biogenesis is stimulated by muscular activity834

Fuel choice during exercise is determined by the intensity and duration of activity835

27.5 Food Intake and Starvation Induce Metabolic Changes836

The starved-fed cycle is the physiological response to a fast837

Metabolic adaptations in prolonged starvation minimize protein degradation838

27.6 Ethanol Alters Energy Metabolism in the Liver840

Ethanol metabolism leads to an excess of NADH840

Excess ethanol consumption disrupts vitamin metabolism842

Chapter 28 DNA Replication，Repair，and Recombination849

28.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template850

DNA polymerases require a template and a primer850

All DNA polymerases have structural features in common851

Two bound metal ions participate in the polymerase reaction851

The specificity of replication is dictated by complementarity of shape between bases852

An RNA primer synthesized by primase enables DNA synthesis to begin853

One strand of DNA is made continuously，whereas the other strand is synthesized in fragments853

DNA ligase joins ends of DNA in duplex regions854

The separation of DNA strands requires specific helicases and ATP hydrolysis854

28.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases855

The linking number of DNA，a topological property，determines the degree of supercoiling856

Topoisomerases prepare the double helix for unwinding858

Type Ⅰ topoisomerases relax supercoiled structures858

Type Ⅱ topoisomerases can introduce negative supercoils through coupling to ATP hydrolysis859

28.3 DNA Replication Is Highly Coordinated861

DNA replication requires highly processive polymerases861

The leading and lagging strands are synthesized in a coordinated fashion862

DNA replication in Escherichia coli begins at a unique site864

DNA synthesis in eukaryotes is initiated at multiple sites865

Telomeres are unique structures at the ends of linear chromosomes866

Telomeres are replicated by telomerase，a specialized polymerase that carries its own RNA template867

28.4 Many Types of DNA Damage Can Be Repaired867

Eerrors can arise in DNA replication867

Bases can be damaged by oxidizing agents，alkylating agents，and light868

DNA damage can be detected and repaired by a variety of systems869

The presence of thymine instead of uracil in DNA permits the repair of deaminated cytosine871

Some genetic diseases are caused by the expansion of repeats of three nucleotides872

Many cancers are caused by the defective repair of DNA872

Many potential carcinogens can be detected by their mutagenic action on bacteria873

28.5 DNA Recombination Plays Important Roles in Replication，Repair，and Other Processes874

RecA can initiate recombination by promoting strand invasion874

Some recombination reactions proceed through Holliday-junction intermediates875

Chapter 29 RNA Synthesis and Processing883

RNA synthesis comprises three stages：Initiation，elongation，and termination884

29.1 RNA Polymerases Catalyze Transcription885

RNA chains are formed de novo and grow in the 5’-to-3’ direction886

RNA polymerases backtrack and correct errors888

RNA polymerase binds to promoter sites on the DNA template to initiate transcription888

Sigma subunits of RNA polymerase recognize promoter sites889

RNA polymerases must unwind the template double helix for transcription to take place890

Elongation takes place at transcription bubbles that move along the DNA template890

Sequences within the newly transcribed RNA signal termination891

Some messenger RNAs directly sense metabolite concentrations892

The rho protein helps to terminate the transcription of some genes892

Some antibiotics inhibit transcription893

Precursors of transfer and ribosomal RNA are cleaved and chemically modified after transcription in prokaryotes895

29.2 Transcription in Eukaryotes Is Highly Regulated896

Three types of RNA polymerase synthesize RNA in eukaryotic cells897

Three common elements can be found in the RNA polymerase Ⅱ promoter region898

The TFIID protein complex initiates the assembly of the active transcription complex899

Multiple transcription factors interact with eukaryotic promoters900

Enhancer sequences can stimulate transcription at start sites thousands of bases away900

29.3 The Transcription Products of Eukaryotic Polymerases Are Processed901

RNA polymerase Ⅰ produces three ribosomal RNAs901

RNA polymerase Ⅲ produces transfer RNA902

The product of RNA polymerase Ⅱ，the pre-mRNA transcript，acquires a 5’ cap and a 3’ poly（A）tail902

Small regulatory RNAs are cleaved from larger precursors904

RNA editing changes the proteins encoded by mRNA904

Sequences at the ends of introns specify splice sites in mRNA precursors905

Splicing consists of two sequential transesterification reactions906

Small nuclear RNAs in spliceosomes catalyze the splicing of mRNA precursors907

Transcription and processing of mRNA are coupled909

Mutations that affect pre-mRNA splicing cause disease909

Most human pre-mRNAS can be spliced in alternative ways to yield different proteins910

29.4 The Discovery of Catalytic RNA Was Revealing in Regard to Both Mechanism and Evolution911

Chapter 30 Protein Synthesis921

30.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences922

The synthesis of long proteins requires a low error frequency922

Transfer RNA molecules have a common design923

Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing925

30.2 Aminoacyl Transfer RNA Synthetases Read the Genetic Code927

Amino acids are first activated by adenylation927

Aminoacyl-tRNA synthetases have highly discriminating amino acid activation sites928

Proofreading by aminoacyl-tRNA synthetases increases the fidelity of protein synthesis929

Synthetases recognize various features of transfer RNA molecules930

Aminoacyl-tRNA synthetases can be divided into two classes931

30.3 The Ribosome Is the Site of Protein Synthesis931

Ribosomal RNAs（5S，16S，and 23S rRNA）play a central role in protein synthesis932

Ribosomes have three tRNA-binding sites that bridge the 30s and 50s subunits934

The start signal is usually AUG preceded by several bases that pair with 16S rRNA934

Bacterial protein synthesis is initiated by formylmethionyl transfer RNA935

Formylmethionyl-tRNAf is placed in the P site of the ribosome in the formation of the 70S initiation complex936

Elongation factors deliver aminoacyl-tRNA to the ribosome936

Peptidyl transferase catalyzes peptide-bond synthesis937

The formation of a peptide bond is followed by the GTP-driven translocation of tRNAs and mRNA938

Protein synthesis is terminated by release factors that read stop codons940

30.4 Eukaryotic Protein Synthesis Differs from Prokaryotic Protein Synthesis Primarily in Translation Initiation941

Mutations in initiation factor 2 cause a curious pathological condition942

30.5 A Variety of Antibiotics and Toxins Can Inhibit Protein Synthesis943

Some antibiotics inhibit protein synthesis943

Diphtheria toxin blocks protein synthesis in eukary