BIOCHEMISTRY INTERNATIONAL SEVENTH EDITIONPDF电子书下载

Part Ⅰ THE MOLECULAR DESIGN OF LIFE 1

Chapter 1 Biochemistry：An Evolving Science 1

1.1 Biochemical Unity Underlies Biological Diversity 1

1.2 DNA Illustrates the Interplay Between Form and Function 4

DNA is constructed from four building blocks 4

Two single strands of DNA combine to form a double helix 5

DNA structure explains heredity and the storage of information 5

1.3 Concepts from Chemistry Explain the Properties of Biological Molecules 6

The double helix can form from its component strands 6

Covalent and noncovalent bonds are important for the structure and stability of biological molecules 7

The double helix is an expression of the rules of chemistry 10

The laws of thermodynamics govern the behavior of biochemical systems 11

Heat is released in the formation of the double helix 12

Acid base reactions are central in many biochemical processes 13

Acid-base reactions can disrupt the double helix 14

Buffers regulate pH in organisms and in the laboratory 15

1.4 The Genomic Revolution Is Transforming Biochemistry and Medicine 17

The sequencing of the human genome is a landmark in human history 17

Genome sequences encode proteins and patterns of expression 18

Individuality depends on the interplay between genes and environment 19

APPENDIX：Visualizing Molecular Structures Ⅰ：Small Molecules 21

Chapter 2 Protein Composition and Structure 25

2.1 Proteins Are Built from a Repertoire of 20 Amino Acids 27

2.2 Primary Structure：Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains 33

Proteins have unique amino acid sequences specified by genes 35

Polypeptide chains are flexible yet conformationally restricted 36

2.3 Secondary Structure：Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix，the Beta Sheet，and Turns and Loops 38

The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds 38

Beta sheets are stabilized by hydrogen bonding between polypeptide strands 40

Polypeptide chains can change direction by making reverse turns and loops 42

Fibrous proteins provide structural support for cells and tissues 43

2.4 Tertiary Structure：Water-Soluble Proteins Fold into Compact Structures with Nonpolar Cores 45

2.5 Quaternary Structure：Polypeptide Chains Can Assemble into Multisubunit Structures 48

2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure 49

Amino acids have different propensities for forming alpha helices，beta sheets，and beta turns 50

Protein folding is a highly cooperative process 52

Proteins fold by progressive stabilization of intermediates rather than by random search 52

Prediction of three-dimensional structure from sequence remains a great challenge 54

Some proteins are inherently unstructured and can exist in multiple conformations 54

Protein misfolding and aggregation are associated with some neurological diseases 55

Protein modification and cleavage confer new capabilities 57

APPENDIX：Visualizing Molecular Structures Ⅱ：Proteins 60

Chapter 3 Exploring Proteins and Proteomes 67

The proteome is the functional representation of the genome 68

3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function 68

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

Proteins must be released from the cell to be purified 69

Proteins can be purified according to solubility，size，charge，and binding affinity 70

Proteins can be separated by gel electrophoresis and displayed 73

A protein purification scheme can be quantitatively evaluated 77

Ultracentrifugation is valuable for separating biomolecules and determining their masses 78

Protein purification can be made easier with the use of recombinant DNA technology 80

3.2 Amino Acid Sequences of Proteins Can Be Determined Experimentally 81

Peptide sequences can be determined by automated Edman degradation 82

Proteins can be specifically cleaved into small peptides to facilitate analysis 84

Genomic and proteomic methods are complementary 86

3.3 Immunology Provides Important Techniques with Which to investigate Proteins 86

Antibodies to specific proteins can be generated 86

Monoclonal antibodies with virtually any desired specificity can be readily prepared 88

Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay 90

Western blotting permits the detection of proteins separated by gel electrophoresis 91

Fluorescent markers make the visualization of proteins in the cell possible 92

3.4 Mass Spectrometry Is a Powerful Technique for the Identification of Peptides and Proteins 93

The mass of a protein can be precisely determined by mass spectrometry 93

Peptides can be sequenced by mass spectrometry 95

Individual proteins can be identified by mass spectrometry 96

3.5 Peptides Can Be Synthesized by Automated Solid-Phase Methods 97

3.6 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography and NMR Spectroscopy 100

X-ray crystallography reveals three-dimensional structure in atomic detail 100

Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution 103

Chapter 4 DNA，RNA，and the Flow of Information 113

4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar-Phosphate Backbone 114

RNA and DNA differ in the sugar component and one of the bases 114

Nucleotides are the monomeric units of nucleic acids 115

DNA molecules are very long 117

4.2 A Pair of Nucleic Acid Chains with Complementary Sequences Can Form a Double-Helical Structure 117

The double helix is stabilized by hydrogen bonds and van der Waals interactions 117

DNA can assume a variety of structural forms 119

Z-DNA is a left-handed double helix in which backbone phosphates zigzag 120

Some DNA molecules are circular and supercoiled 121

Single-stranded nucleic acids can adopt elaborate structures 121

4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information 122

Differences in DNA density established the validity of the semiconservative-replication hypothesis 123

The double helix can be reversibly melted 124

4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates 125

DNA polymerase catalyzes phosphodiester-bridge formation 125

The genes of some viruses are made of RNA 126

4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules 127

Several kinds of RNA play key roles in gene expression 127

All cellular RNA is synthesized by RNA polymerases 128

RNA polymerases take instructions from DNA templates 130

Transcription begins near promoter sites and ends at terminator sites 130

Transfer RNAs are the adaptor molecules in protein synthesis 131

4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point 132

Major features of the genetic code 133

Messenger RNA contains start and stop signals for protein synthesis 134

The genetic code is nearly universal 135

4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons 135

RNA processing generates mature RNA 136

Many exons encode protein domains 137

Chapter 5 Exploring Genes and Genomes 145

5.1 The Exploration of Genes Relies on Key Tools 146

Restriction enzymes split DNA into specific fragments 147

Restriction fragments can be separated by gel electrophoresis and visualized 147

DNA can be sequenced by controlled termination of replication 149

DNA probes and genes can be synthesized by automated solid-phase methods 150

Selected DNA sequences can be greatly amplified by the polymerase chain reaction 151

PCR is a powerful technique in medical diagnostics，forensics，and studies of molecular evolution 152

The tools for recombinant DNA technology have been used to identify disease-causing mutations 153

5.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology 154

Restriction enzymes and DNA ligase are key tools in forming recombinant DNA molecules 154

Plasmids and lambda phage are choice vectors for DNA cloning in bacteria 155

Bacterial and yeast artificial chromosomes 157

Specific genes can be cloned from digests of genomic DNA 157

Complementary DNA prepared from mRNA can be expressed in host cells 160

Proteins with new functions can be created through directed changes in DNA 162

Recombinant methods enable the exploration of the functional effects of disease-causing mutations 163

5.3 Complete Genomes Have Been Sequenced and Analyzed 163

The genomes of organisms ranging from bacteria to multicellular eukaryotes have been sequenced 164

The sequencing of the human genome has been finished 165

Next-generation sequencing methods enable the rapid determination of a whole genome sequence 166

Comparative genomics has become a powerful research tool 166

5.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision 167

Gene-expression levels can be comprehensively examined 167

New genes inserted into eukaryotic cells can be efficiently expressed 169

Transgenic animals harbor and express genes introduced into their germ lines 170

Gene disruption provides clues to gene function 170

RNA interference provides an additional tool for disrupting gene expression 171

Tumor-inducing plasmids can be used to introduce new genes into plant cells 172

Human gene therapy holds great promise for medicine 173

Chapter 6 Exploring Evolution and Bioinformatics 181

6.1 Homologs Are Descended from a Common Ancestor 182

6.2 Statistical Analysis of Sequence Alignments Can Detect Homology 183

The statistical significance of alignments can be estimated by shuffling 185

Distant evolutionary relationships can be detected through the use of substitution matrices 186

Databases can be searched to identify homologous sequences 189

6.3 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships 190

Tertiary structure is more conserved than primary structure 191

Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments 192

Repeated motifs can be detected by aligning sequences with themselves 192

Convergent evolution illustrates common solutions to biochemical challenges 193

Comparison of RNA sequences can be a source of insight into RNA secondary structures 194

6.4 Evolutionary Trees Can Be Constructed on the Basis of Sequence Information 195

6.5 Modern Techniques Make the Experimental Exploration of Evolution Possible 196

Ancient DNA can sometimes be amplified and sequenced 196

Molecular evolution can be examined experimentally 197

Chapter 7 Hemoglobin：Portrait of a Protein in Action 203

7.1 Myoglobin and Hemoglobin Bind Oxygen at Iron Atoms in Heme 204

Changes in heme electronic structure upon oxygen binding are the basis for functional imaging studies 205

The structure of myoglobin prevents the release of reactive oxygen species 206

Human hemoglobin is an assembly of four myoglobin-like subunits 207

7.2 Hemoglobin Binds Oxygen Cooperatively 207

Oxygen binding markedly changes the quaternary structure of hemoglobin 209

Hemoglobin cooperativity can be potentially explained by several models 210

Structural changes at the heme groups are transmitted to the α1β1-α2β2 interface 212

2，3-Bisphosphoglycerate in red cells is crucial in determining the oxygen affinity of hemoglobin 212

Carbon monoxide can disrupt oxygen transport by hemoglobin 213

7.3 Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen：The Bohr Effect 214

7.4 Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease 216

Sickle-cell anemia results from the aggregation of mutated deoxyhemoglobin molecules 217

Thalassemia is caused by an imbalanced production of hemoglobin chains 218

The accumulation of free alpha-hemoglobin chains is prevented 219

Additional globins are encoded in the human genome 219

APPENDIX：Binding Models Can Be Formulated in Quantitative Terms：the Hill Plot and the Concerted Model 221

Chapter 8 Enzymes：Basic Concepts and Kinetics 227

8.1 Enzymes Are Powerful and Highly Specific Catalysts 228

Many enzymes require cofactors for activity 229

Enzymes can transform energy from one form into another 229

8.2 Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes 230

The free-energy change provides information about the spontaneity but not the rate of a reaction 230

The standard free-energy change of a reaction is related to the equilibrium constant 231

Enzymes alter only the reaction rate and not the reaction equilibrium 232

8.3 Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State 233

The formation of an enzyme-substrate complex is the first step in enzymatic catalysis 234

The active sites of enzymes have some common features 235

The binding energy between enzyme and substrate is important for catalysis 237

8.4 The Michaelis-Menten Equation Describes the Kinetic Properties of Many Enzymes 237

Kinetics is the study of reaction rates 237

The steady-state assumption facilitates a description of enzyme kinetics 238

Variations in KM can have physiological consequences 240

KM and Vmax values can be determined by several means 240

KM and Vmax values are important enzyme characteristics 241

kcat/KM is a measure of catalytic efficiency 242

Most biochemical reactions include multiple substrates 243

Allosteric enzymes do not obey Michaelis-Menten kinetics 245

8.5 Enzymes Can Be Inhibited by Specific Molecules 246

Reversible inhibitors are kinetically distinguishable 247

Irreversible inhibitors can be used to map the active site 249

Transition-state analogs are potent inhibitors of enzymes 251

Catalytic antibodies demonstrate the importance of selective binding of the transition state to enzymatic activity 251

Penicillin irreversibly inactivates a key enzyme in bacterial cell-wall synthesis 252

8.6 Enzymes Can Be Studied One Molecule at a Time 254

APPENDIX：Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze 256

Chapter 9 Catalytic Strategies 261

A few basic catalytic principles are used by many enzymes 262

9.1 Proteases Facilitate a Fundamentally Difficult Reaction 263

Chymotrypsin possesses a highly reactive serine residue 263

Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate 264

Serine is part of a catalytic triad that also includes histidine and aspartate 265

Catalytic triads are found in other hydrolytic enzymes 268

The catalytic triad has been dissected by site-directed mutagenesis 270

Cysteine，aspartyl，and metalloproteases are other major classes of peptide-cleaving enzymes 271

Protease inhibitors are important drugs 272

9.2 Carbonic Anhydrases Make a Fast Reaction Faster 274

Carbonic anhydrase contains a bound zinc ion essential for catalytic activity 275

Catalysis entails zinc activation of a water molecule 276

A proton shuttle facilitates rapid regeneration of the active form of the enzyme 277

Convergent evolution has generated zinc-based active sites in different carbonic anhydrases 279

9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions 279

Cleavage is by in-line displacement of 3’-oxygen from phosphorus by magnesium-activated water 280

Restriction enzymes require magnesium for catalytic activity 282

The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules，ensuring specificity 283

Host-cell DNA is protected by the addition of methyl groups to specific bases 285

Type Ⅱ restriction enzymes have a catalytic core in common and are probably related by horizontal gene transfer 286

9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work 287

ATP hydrolysis proceeds by the attack of water on the gamma-phosphoryl group 287

Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change 288

The altered conformation of myosin persists for a substantial period of time 290

Myosins are a family of enzymes containing P-loop structures 291

Chapter 10 Regulatory Strategies 299

10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway 300

Allosterically regulated enzymes do not follow Michaelis-Menten kinetics 301

ATCase consists of separable catalytic and regulatory subunits 301

Allosteric interactions in ATCase are mediated by large changes in quaternary structure 302

Allosteric regulators modulate the T-to-R equilibrium 305

10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages 306

10.3 Covalent Modification Is a Means of Regulating Enzyme Activity 307

Kinases and phosphatases control the extent of protein phosphorylation 308

Phosphorylation is a highly effective means of regulating the activities of target proteins 310

Cyclic AMP activates protein kinase A by altering the quaternary structure 311

ATP and the target protein bind to a deep cleft in the catalytic subunit of protein kinase A 312

10.4 Many Enzymes Are Activated by Specific Proteolytic Cleavage 312

Chymotrypsinogen is activated by specific cleavage of a single peptide bond 313

Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site 314

The generation of trypsin from trypsinogen leads to the activation of other zymogens 315

Some proteolytic enzymes have specific inhibitors 316

Blood clotting is accomplished by a cascade of zymogen activations 317

Fibrinogen is converted by thrombin into a fibrin clot 318

Prothrombin is readied for activation by a vitamin K-dependent modification 320

Hemophilia revealed an early step in clotting 321

The clotting process must be precisely regulated 321

Chapter 11 Carbohydrates 329

11.1 Monosaccharides Are the Simplest Carbohydrates 330

Many common sugars exist in cyclic forms 332

Pyranose and furanose rings can assume different conformations 334

Glucose is a reducing sugar 335

Monosaccharides are joined to alcohols and amines through glycosidic bonds 336

Phosphorylated sugars are key intermediates in energy generation and biosyntheses 336

11.2 Monosaccharides Are Linked to Form Complex Carbohydrates 337

Sucrose，lactose，and maltose are the common disaccharides 337

Glycogen and starch are storage forms of glucose 338

Cellulose，a structural component of plants，is made of chains of glucose 338

11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins 339

Carbohydrates can be linked to proteins through asparagine（N-linked）or through serine or threonine（O-linked）residues 340

The glycoprotein erythropoietin is a vital hormone 340

Proteoglycans，composed of polysaccharides and protein，have important structural roles 341

Proteoglycans are important components of cartilage 342

Mucins are glycoprotein components of mucus 343

Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex 343

Specific enzymes are responsible for oligosaccharide assembly 345

Blood groups are based on protein glycosylation patterns 345

Errors in glycosylation can result in pathological conditions 346

Oligosaccharides can be “sequenced” 346

11.4 Lectins Are Specific Carbohydrate-Binding Proteins 347

Lectins promote interactions between cells 348

Lectins are organized into different classes 348

Influenza virus binds to sialic acid residues 349

Chapter 12 Lipids and Cell Membranes 357

Many common features underlie the diversity of biological membranes 358

12.1 Fatty Acids Are Key Constituents of Lipids 358

Fatty acid names are based on their parent hydrocarbons 358

Fatty acids vary in chain length and degree of unsaturation 359

12.2 There Are Three Common Types of Membrane Lipids 360

Phospholipids are the major class of membrane lipids 360

Membrane lipids can include carbohydrate moieties 361

Cholesterol is a lipid based on a steroid nucleus 362

Archaeal membranes are built from ether lipids with branched chains 362

A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety 363

12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media 364

Lipid vesicles can be formed from phospholipids 365

Lipid bilayers are highly impermeable to ions and most polar molecules 366

12.4 Proteins Carry Out Most Membrane Processes 367

Proteins associate with the lipid bilayer in a variety of ways 367

Proteins interact with membranes in a variety of ways 368

Some proteins associate with membranes through covalently attached hydrophobic groups 371

Transmembrane helices can be accurately predicted from amino acid sequences 371

12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane 373

The fluid mosaic model allows lateral movement but not rotation through the membrane 374

Membrane fluidity is controlled by fatty acid composition and cholesterol content 374

Lipid rafts are highly dynamic complexes formed between cholesterol and specific lipids 375

All biological membranes are asymmetric 375

12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes 376

Chapter 13 Membrane Channels and Pumps 383

The expression of transporters largely defines the metabolic activities of a given cell type 384

13.1 The Transport of Molecules Across a Membrane May Be Active or Passive 384

Many molecules require protein transporters to cross membranes 384

Free energy stored in concentration gradients can be quantified 385

13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes 386

P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes 386

Digitalis specifically inhibits the Na＋-K＋pump by blocking its dephosphorylation 389

P-type ATPases are evolutionarily conserved and play a wide range of roles 390

Multidrug resistance highlights a family of membrane pumps with ATP-binding cassette domains 390

13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another 392

13.4 Specific Channels Can Rapidly Transport Ions Across Membranes 394

Action potentials are mediated by transient changes in Na＋and K＋permeability 394

Patch-clamp conductance measurements reveal the activities of single channels 395

The structure of a potassium ion channel is an archetype for many ion-channel structures 395

The structure of the potassium ion channel reveals the basis of ion specificity 396

The structure of the potassium ion channel explains its rapid rate of transport 399

Voltage gating requires substantial conformational changes in specific ion-channel domains 399

A channel can be activated by occlusion of the pore：the ball-and-chain model 400

The acetylcholine receptor is an archetype for ligand-gated ion channels 401

Action potentials integrate the activities of several ion channels working in concert 402

Disruption of ion channels by mutations or chemicals can be potentially life threatening 404

13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells 405

13.6 Specific Channels Increase the Permeability of Some Membranes to Water 406

Chapter 14 Signal-Transduction Pathways 415

Signal transduction depends on molecular circuits 416

14.1 Heterotrimeric G Proteins Transmit Signals and Reset Themselves 417

Ligand binding to 7TM receptors leads to the activation of heterotrimeric G proteins 419

Activated G proteins transmit signals by binding to other proteins 420

Cyclic AMP stimulates the phosphorylation of many target proteins by activating protein kinase A 420

G proteins spontaneously reset themselves through GTP hydrolysis 421

Some 7TM receptors activate the phosphoinositide cascade 422

Calcium ion is a widely used second messenger 423

Calcium ion often activates the regulatory protein calmodulin 424

14.2 Insulin Signaling：Phosphorylation Cascades Are Central to Many Signal-Transduction Processes 425

The insulin receptor is a dimer that closes around a bound insulin molecule 426

Insulin binding results in the cross-phosphorylation and activation of the insulin receptor 426

The activated insulin-receptor kinase initiates a kinase cascade 426

Insulin signaling is terminated by the action of phosphatases 429

14.3 EGF Signaling：Signal-Transduction Pathways Are Poised to Respond 429

EGF binding results in the dimerization of the eGF receptor 429

The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail 431

EGF signaling leads to the activation of Ras，a small G protein 431

Activated Ras initiates a protein kinase cascade 432

EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras 432

14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways 433

14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases 434

Monoclonal antibodies can be used to inhibit signal-transduction pathways activated in tumors 434

Protein kinase inhibitors can be effective anticancer drugs 435

Cholera and whooping cough are due to altered G-protein activity 435

Part Ⅱ TRANSDUCING AND STORING ENERGY 443

Chapter 15 Metabolism：Basic Concepts and Design 443

15.1 Metabolism Is Composed of Many Coupled，Interconnecting Reactions 444

Metabolism consists of energy-yielding and energy-requiring reactions 444

A thermodynamically unfavorable reaction can be driven by a favorable reaction 445

15.2 ATP Is the Universal Currency of Free Energy in Biological Systems 446

ATP hydrolysis is exergonic 446

ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions 447

The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products 449

Phosphoryl-transfer potential is an important form of cellular energy transformation 450

15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy 451

Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis 452

Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis 453

Energy from foodstuffs is extracted in three stages 453

15.4 Metabolic Pathways Contain Many Recurring Motifs 454

Activated carriers exemplify the modular design and economy of metabolism 454

Many activated carriers are derived from vitamins 457

Key reactions are reiterated throughout metabolism 459

Metabolic processes are regulated in three principal ways 461

Aspects of metabolism may have evolved from an RNA world 463

Chapter 16 Glycolysis and Gluconeogenesis 469

Glucose is generated from dietary carbohydrates 470

Glucose is an important fuel for most organisms 471

16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms 471

Hexokinase traps glucose in the cell and begins glycolysis 471

Fructose 1，6-bisphosphate is generated from glucose 6-phosphate 473

The six-carbon sugar is cleaved into two three-carbon fragments 474

Mechanism：Triose phosphate isomerase salvages a three-carbon fragment 475

The oxidation of an aldehyde to an acid powers the formation of a compound with high phosphoryl-transfer potential 476

Mechanism：Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate 478

ATP is formed by phosphoryl transfer from 1，3-bisphosphoglycerate 479

Additional ATP is generated with the formation of pyruvate 480

Two ATP molecules are formed in the conversion of glucose into pyruvate 481

NAD＋is regenerated from the metabolism of pyruvate 482

Fermentations provide usable energy in the absence of oxygen 484

The binding site for NAD＋is similar in many dehydrogenases 485

Fructose and galactose are converted into glycolytic intermediates 485

Many adults are intolerant of milk because they are deficient in lactase 487

Galactose is highly toxic if the transferase is missing 488

16.2 The Glycolytic Pathway Is Tightly Controlled 488

Glycolysis in muscle is regulated to meet the need for ATP 489

The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver 490

A family of transporters enables glucose to enter and leave animal cells 493

Cancer and exercise training affect glycolysis in a similar fashion 494

16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors 495

Gluconeogenesis is not a reversal of glycolysis 497

The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate 498

Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate 499

The conversion of fructose 1，6-bisphosphate into fructose 6-phosphate and orthophosphate is an irreversible step 500

The generation of free glucose is an important control point 500

Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate 501

16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated 502

Energy charge determines whether glycolysis or gluconeogenesis will be most active 502

The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration 503

Substrate cycles amplify metabolic signals and produce heat 505

Lactate and alanine formed by contracting muscle are used by other organs 505

Glycolysis and gluconeogenesis are evolutionarily intertwined 507

Chapter 17 The Citric Acid Cycle 515

The citric acid cycle harvests high-energy electrons 516

17.1 Pyruvate Dehydrogenase Links Glycolysis to the Citric Acid Cycle 517

Mechanism：The synthesis of acetyl coenzyme a frompyruvate requires three enzymes and five coenzymes 518

Flexible linkages allow lipoamide to move between different active sites 520

17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units 521

Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A 522

Mechanism：The mechanism of citrate synthase prevents undesirable reactions 522

Citrate is isomerized into isocitrate 524

Isocitrate is oxidized and decarboxylated to alpha-ketoglutarate 524

Succinyl coenzyme A is formed by the oxidative decarboxylation of alpha-ketoglutarate 525

A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A 525

Mechanism：Succinyl coenzyme A synthetase transforms types of biochemical energy 526

Oxaloacetate is regenerated by the oxidation of succinate 527

The citric acid cycle produces high-transfer-potential electrons，ATP，and CO2 528

17.3 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled 530

The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation 531

The citric acid cycle is controlled at several points 532

Defects in the citric acid cycle contribute to the development of cancer 533

17.4 The Citric Acid Cycle Is a Source of Biosynthetic Precursors 534

The citric acid cycle must be capable of being rapidly replenished 534

The disruption of pyruvate metabolism is the cause of beriberi and poisoning by mercury and arsenic 535

The citric acid cycle may have evolved from preexisting pathways 536

17.5 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate 536

Chapter 18 Oxidative Phosphorylation 543

18.1 Eukaryotic Oxidative Phosphorylation Takes Place in Mitochondria 544

Mitochondria are bounded by a double membrane 544

Mitochondria are the result of an endosymbiotic event 545

18.2 Oxidative Phosphorylation Depends on Electron Transfer 546

The electron-transfer potential of an electron is measured as redox potential 546

A 1.14-volt potential difference between NADH and molecular oxygen drives electron transport through the chain and favors the formation of a proton gradient 548

18.3 The Respiratory Chain Consists of Four Complexes：Three Proton Pumps and a Physical Link to the Citric Acid Cycle 549

The high-potential electrons of NADH enter the respiratory chain at NADH-Qoxidoreductase 551

Ubiquinol is the entry point for electrons from FADH2 of flavoproteins 553

Electrons flow from ubiquinol to cytochrome c through Q-cytochrome c oxidoreductase 553

The Qcycle funnels electrons from a two-electron carrier to a one-electron carrier and pumps protons 554

Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water 555

Toxic derivatives of molecular oxygen such as superoxide radical are scavenged by protective enzymes 558

Electrons can be transferred between groups that are not in contact 560

The conformation of cytochrome c has remained essentially constant for more than a billion years 561

18.4 A Proton Gradient Powers the Synthesis of ATP 561

ATP synthase is composed of a proton-conducting unit and a catalytic unit 563

Proton flow through ATP synthase leads to the release of tightly bound ATP：The binding-change mechanism 564

Rotational catalysis is the world’s smallest molecular motor 565

Proton flow around the c ring powers ATP synthesis 566

ATP synthase and G proteins have several common features 568

18.5 Many Shuttles Allow Movement Across Mitochondrial Membranes 568

Electrons from cytoplasmic NADH enter mitochondria by shuttles 569

The entry of ADP into mitochondria is coupled to the exit of ATP by ATP-ADP translocase 570

Mitochondrial transporters for metabolites have a common tripartite structure 571

18.6 The Regulation of Cellular Respiration Is Governed Primarily by the Need for ATP 572

The complete oxidation of glucose yields about 30 molecules of ATP 572

The rate of oxidative phosphorylation is determined by the need for ATP 573

Regulated uncoupling leads to the generation of heat 574

Oxidative phosphorylation can be inhibited at many stages 576

Mitochondrial diseases are being discovered 576

Mitochondria play a key role in apoptosis 577

Power transmission by proton gradients is a central motif of bioenergetics 577

Chapter 19 The Light Reactions of Photosynthesis 585

Photosynthesis converts light energy into chemical energy 586

19.1 Photosynthesis Takes Place in Chloroplasts 587

The primary events of photosynthesis take place in thylakoid membranes 587

Chloroplasts arose from an endosymbiotic event 588

19.2 Light Absorption by Chlorophyll Induces Electron Transfer 588

A special pair of chlorophylls initiate charge separation 589

Cyclic electron flow reduces the cytochrome of the reaction center 592

19.3 Two Photosystems Generate a Proton Gradient and NADPH in Oxygenic Photosynthesis 592

Photosystem Ⅱ transfers electrons from water to plastoquinone and generates a proton gradient 592

Cytochrome bf links photosystem Ⅱ to photosystem Ⅰ 595

Photosystem I uses light energy to generate reduced ferredoxin，a powerful reductant 595

Ferredoxin-NADP＋reductase converts NADP＋into NADPH 596

19.4 A Proton Gradient Across the Thylakoid Membrane Drives ATP Synthesis 597

The ATP synthase of chloroplasts closely resembles those of mitochondria and prokaryotes 598

Cyclic electron flow through photosystem I leads to the production of ATP instead of NADPH 599

The absorption of eight photons yields one O2，two NADPH，and three ATP molecules 600

19.5 Accessory Pigments Funnel Energy into Reaction Centers 601

Resonance energy transfer allows energy to move from the site of initial absorbance to the reaction center 601

Light-harvesting complexes contain additional chlorophylls and carotinoids 602

The components of photosynthesis are highly organized 603

Many herbicides inhibit the light reactions of photosynthesis 604

19.6 The Ability to Convert Light into Chemical Energy Is Ancient 604

Chapter 20 The Calvin Cycle and Pentose Phosphate Pathway 609

20.1 The Calvin Cycle Synthesizes Hexoses from Carbon Dioxide and Water 610

Carbon dioxide reacts with ribulose 1，5-bisphosphate to form two molecules of 3-phosphoglycerate 611

Rubisco activity depends on magnesium and carbamate 612

Rubisco also catalyzes a wasteful oxygenase reaction：Catalytic imperfection 613

Hexose phosphates are made from phosphoglycerate，and ribulose 1，5-bisphosphate is regenerated 614

Three ATP and two NADPH molecules are used to bring carbon dioxide to the level of a hexose 617

Starch and sucrose are the major carbohydrate stores in plants 617

20.2 The Activity of the Calvin Cycle Depends on Environmental Conditions 617

Rubisco is activated by light-driven changes in proton and magnesium ion concentrations 618

Thioredoxin plays a key role in regulating the Calvin cycle 618

The C4 pathway of tropical plants accelerates photosynthesis by concentrating carbon dioxide 619

Crassulacean acid metabolism permits growth in arid ecosystems 620

20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes Five-Carbon Sugars 621

Two molecules of NADPH are generated in the conversion of glucose 6-phosphate into ribulose 5-phosphate 621

The pentose phosphate pathway and glycolysis are linked by transketolase and transaldolase 621

Mechanism：Transketolase and transaldolase stabilize carbanionic intermediates by different mechanisms 624

20.4 The Metabolism of Glucose 6-phosphate by the Pentose Phosphate Pathway Is Coordinated with Glycolysis 626

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 ATP 627

Through the looking-glass：The Calvin cycle and the pentose phosphate pathway are mirror images 629

20.5 Glucose 6-phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species 629

Glucose 6-phosphate dehydrogenase deficiency causes a drug-induced hemolytic anemia 629

A deficiency of glucose 6-phosphate dehydrogenase confers an evolutionary advantage in some circumstances 631

Chapter 21 Glycogen Metabolism 637

Glycogen metabolism is the regulated release and storage of glucose 638

21.1 Glycogen Breakdown Requires the Interplay of Several Enzymes 639

Phosphorylase catalyzes the phosphorolytic cleavage of glycogen to release glucose 1-phosphate 639

Mechanism：Pyridoxal phosphate participates in the phosphorolytic cleavage of glycogen 640

A debranching enzyme also is needed for the breakdown of glycogen 641

Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate 642

The liver contains glucose 6-phosphatase，a hydrolytic enzyme absent from muscle 643

21.2 Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation 643

Muscle phosphorylase is regulated by the intracellular energy charge 643

Liver phosphorylase produces glucose for use by other tissues 645

Phosphorylase kinase is activated by phosphorylation and calcium ions 645

21.3 Epinephrine and Glucagon Signal the Need for Glycogen Breakdown 646

G proteins transmit the signal for the initiation of glycogen breakdown 646

Glycogen breakdown must be rapidly turned off when necessary 648

The regulation of glycogen phosphorylase became more sophisticated as the enzyme evolved 649

21.4 Glycogen Is Synthesized and Degraded by Different Pathways 649

UDP-glucose is an activated form of glucose 649

Glycogen synthase catalyzes the transfer of glucose from UDP-glucose to a growing chain 650

A branching enzyme forms α-1，6 linkages 651

Glycogen synthase is the key regulatory enzyme in glycogen synthesis 651

Glycogen is an efficient storage form of glucose 651

21.5 Glycogen Breakdown and Synthesis Are Reciprocally Regulated 652

Protein phosphatase 1 reverses the regulatory effects of kinases on glycogen metabolism 653

Insulin stimulates glycogen synthesis by inactivating glycogen synthase kinase 654

Glycogen metabolism in the liver regulates the blood-glucose level 655

A biochemical understanding of glycogen-storage diseases is possible 656

Chapter 22 Fatty Acid Metabolism 663

Fatty acid degradation and synthesis mirror each other in their chemical reactions 664

22.1 Triacylglycerols Are Highly Concentrated Energy Stores 665

Dietary lipids are digested by pancreatic lipases 665

Dietary lipids are transported in chylomicrons 666

22.2 The Use of Fatty Acids As Fuel Requires Three Stages of Processing 667

Triacylglycerols are hydrolyzed by hormone-stimulated lipases 667

Fatty acids are linked to coenzyme A before they are oxidized 668

Carnitine carries long-chain activated fatty acids into the mitochondrial matrix 669

Acetyl CoA，NADH，and FADH2 are generated in each round of fatty acid oxidation 670

The complete oxidation of palmitate yields 106 molecules of ATP 671

22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation 672

An isomerase and a reductase are required for the oxidation of unsaturated fatty acids 672

Odd-chain fatty acids yield propionyl CoA in the final thiolysis step 673

Vitamin B12 contains a corrin ring and a cobalt atom 674

Mechanism：Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA 675

Fatty acids are also oxidized in peroxisomes 676

Ketone bodies are formed from acetyl CoA when fat breakdown predominates 677

Ketone bodies are a major fuel in some tissues 678

Animals cannot convert fatty acids into glucose 680

22.4 Fatty Acids Are Synthesized by Fatty Acid Synthase 680

Fatty acids are synthesized and degraded by different pathways 680

The formation of malonyl CoA is the committed step in fatty acid synthesis 681

Intermediates in fatty acid synthesis are attached to an acyl carrier protein 681

Fatty acid synthesis consists of a series of condensation，reduction，dehydration，and reduction reactions 682

Fatty acids are synthesized by a multifunctional enzyme complex in animals 683

The synthesis of palmitate requires 8 molecules of acetyl CoA，14 molecules of NADPH，and 7 molecules of ATP 685

Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis 686

Several sources supply NADPH for fatty acid synthesis 686

Fatty acid synthase inhibitors may be useful drugs 687

22.5 The Elongation and Unsaturation of Fatty Acids Are Accomplished by Accessory Enzyme Systems 687

Membrane-bound enzymes generate unsaturated fatty acids 688

Eicosanoid hormones are derived from polyunsaturated fatty acids 688

22.6 Acetyl CoA Carboxylase Plays a Key Role in Controlling Fatty Acid Metabolism 690

Acetyl CoA carboxylase is regulated by conditions in the cell 690

Acetyl CoA carboxylase is regulated by a variety of hormones 690

Chapter 23 Protein Turnover and Amino Acid Catabolism 697

23.1 Proteins Are Degraded to Amino Acids 698

The digestion of dietary proteins begins in the stomach and is completed in the intestine 698

Cellular proteins are degraded at different rates 699

23.2 Protein Turnover Is Tightly Regulated 699

Ubiquitin tags proteins for destruction 699

The proteasome digests the ubiquitin-tagged proteins 701

The ubiquitin pathway and the proteasome have prokaryotic counterparts 701

Protein degradation can be used to regulate biological function 702

23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen 704

Alpha-amino groups are converted into ammonium ions by the oxidative deamination of glutamate 704

Mechanism：Pyridoxal phosphate forms Schiff-base intermediates in aminotransferases 705

Aspartate aminotransferase is an archetypal pyridoxal-dependent transaminase 706

Pyridoxal phosphate enzymes catalyze a wide array of reactions 707

Serine and threonine can be directly deaminated 708

Peripheral tissues transport nitrogen to the liver 708

23.4 Ammonium Ion Is Converted into Urea in Most Terrestrial Vertebrates 709

The urea cycle begins with the formation of carbamoyl phosphate 709

The urea cycle is linked to gluconeogenesis 711

Urea-cycle enzymes are evolutionarily related to enzymes in other metabolic pathways 712

Inherited defects of the urea cycle cause hyperammonemia and can lead to brain damage 712

Urea is not the only means of disposing of excess nitrogen 713

23.5 Carbon Atoms of Degraded Amino Acids Emerge As Major Metabolic Intermediates 714

Pyruvate is an entry point into metabolism for a number of amino acids 715

Oxaloacetate is an entry point into metabolism for aspartate and asparagine 716

Alpha-ketoglutarate is an entry point into metabolism for five-carbon amino acids 716

Succinyl coenzyme A is a point of entry for several nonpolar amino acids 717

Methionine degradation requires the formation of a key methyl donor，S-adenosylmethionine 717

The branched-chain amino acids yield acetyl CoA，acetoacetate，or propionyl CoA 717

Oxygenases are required for the degradation of aromatic amino acids 719

23.6 Inborn Errors of Metabolism Can Disrupt Amino Acid Degradation 721

Part Ⅲ SYNTHESIZING THE MOLECULES OF LIFE 729

Chapter 24 The Biosynthesis of Amino Acids 729

Amino acid synthesis requires solutions to three key biochemical problems 730

24.1 Nitrogen Fixation：Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia 730

The iron-molybdenum cofactor of nitrogenase binds and reduces atmospheric nitrogen 731

Ammonium ion is assimilated into an amino acid through glutamate and glutamine 733

24.2 Amino Acids Are Made from Intermediates of the Citric Acid Cycle and Other Major Pathways 735

Human beings can synthesize some amino acids but must obtain others from the diet 735

Aspartate，alanine，and glutamate are formed by the addition of an amino group to an alpha-ketoacid 736

A common step determines the chirality of all amino acids 737

The formation of asparagine from aspartate requires an adenylated intermediate 737

Glutamate is the precursor of glutamine，proline，and arginine 738

3-Phosphoglycerate is the precursor of serine，cysteine，and glycine 738

Tetrahydrofolate carries activated one-carbon units at several oxidation levels 739

S-Adenosylmethionine is the major donor of methyl groups 740

Cysteine is synthesized from serine and homocysteine 742

High homocysteine levels correlate with vascular disease 743

Shikimate and chorismate are intermediates in the biosynthesis of aromatic amino acids 743

Tryptophan synthase illustrates substrate channeling in enzymatic catalysis 746

24.3 Feedback Inhibition Regulates Amino Acid Biosynthesis 747

Branched pathways require sophisticated regulation 747

An enzymatic cascade modulates the activity of glutamine synthetase 749

24.4 Amino Acids Are Precursors of Many Biomolecules 750

Glutathione，a gamma-glutamyl peptide，serves as a sulfhydryl buffer and an antioxidant 751

Nitric oxide，a short-lived signal molecule，is formed from arginine 751

Porphyrins are synthesized from glycine and succinyl coenzyme A 752

Porphyrins accumulate in some inherited disorders of porphyrin metabolism 754

Chapter 25 Nucleotide Biosynthesis 761

Nucleotides can be synthesized by de novo or salvage pathways 762

25.1 The Pyrimidine Ring Is Assembled de Novo or Recovered by Salvage Pathways 763

Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation 763

The side chain of glutamine can be hydrolyzed to generate ammonia 763

Intermediates can move between active sites by channeling 763

Orotate acquires a ribose ring from PRPP to form a pyrimidine nucleotide and is converted into uridylate 764

Nucleotide mono-，di-，and triphosphates are interconvertible 765

CTP is formed by amination of UTP 765

Salvage pathways recycle pyrimidine bases 766

25.2 Purine Bases Can Be Synthesized de Novo or Recycled by Salvage Pathways 766

The purine ring system is assembled on ribose phosphate 766

The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement 767

AMP and GMP are formed from IMP 769

Enzymes of the purine synthesis pathway associate with one another in vivo 770

Salvage pathways economize intracellular energy expenditure 770

25.3 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides Through a Radical Mechanism 771

Mechanism：A tyrosyl radical is critical to the action of ribonucleotide reductase 771

Stable radicals other than tyrosyl radical are employed by other ribonucleotide reductases 773

Thymidylate is formed by the methylation of deoxyuridylate 774

Dihydrofolate reductase catalyzes the regeneration of tetrahydrofolate，a one-carbon carrier 775

Several valuable anticancer drugs block the synthesis of thymidylate 775

25.4 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition 776

Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase 777

The synthesis of purine nucleotides is controlled by feedback inhibition at several sites 777

The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase 778

25.5 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions 778

The loss of adenosine deaminase activity results in severe combined immunodeficiency 778

Gout is induced by high serum levels of urate 779

Lesch-Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme 780

Folic acid deficiency promotes birth defects such as spina bifida 781

Chapter 26 The Biosynthesis of Membrane Lipids and Steroids 787

26.1 Phosphatidate Is a Common Intermediate in the Synthesis of Phospholipids and Triacylglycerols 788

The synthesis of phospholipids requires an activated intermediate 789

Sphingolipids are synthesized from ceramide 791

Gangliosides are carbohydrate-rich sphingolipids that contain acidic sugars 792

Sphingolipids confer diversity on lipid structure and function 793

Respiratory distress syndrome and Tay-Sachs disease result from the disruption of lipid metabolism 793

Phosphatiditic acid phosphatase is a key regulatory enzyme in lipid metabolism 794

26.2 Cholesterol Is Synthesized from Acetyl Coenzyme A in Three Stages 795

The synthesis of mevalonate，which is activated as isopentenyl pyrophosphate，initiates the synthesis of cholesterol 795

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

Squalene cyclizes to form cholesterol 797

26.3 The Complex Regulation of Cholesterol Biosynthesis Takes Place at Several Levels 798

Lipoproteins transport cholesterol and triacylglycerols throughout the organism 801

The blood levels of certain lipoproteins can serve diagnostic purposes 802

Low-density lipoproteins play a central role in cholesterol metabolism 803

The absence of the LDL receptor leads to hypercholesterolemia and atherosclerosis 804

Mutations in the LDL receptor prevent LDL release and result in receptor destruction 805

HDL appears to protect against arteriosclerosis 806

The clinical management of cholesterol levels can be understood at a biochemical level 807

26.4 Important Derivatives of Cholesterol Include Bile Salts and Steroid Hormones 807

Letters identify the steroid rings and numbers identify the carbon atoms 809

Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2 809

The cytochrome P450 system is widespread and performs a protective function 810

Pregnenolone，a precursor of many other steroids，is formed from cholesterol by cleavage of its side chain 811

Progesterone and corticosteroids are synthesized from pregnenolone 811

Androgens and estrogens are synthesized from pregnenolone 812

Vitamin D is derived from cholesterol by the ring-splitting activity of light 813

Chapter 27 The Integration of Metabolism 821

27.1 Caloric Homeostasis Is a Means of Regulating Body Weight 822

27.2 The Brain Plays a Key Role in Caloric Homeostasis 824

Signals from the gastrointestinal tract induce feelings of satiety 824

Leptin and insulin regulate long-term control over caloric homeostasis 825

Leptin is one of several hormones secreted by adipose tissue 826

Leptin resistance may be a contributing factor to obesity 827

Dieting is used to combat obesity 827

27.3 Diabetes Is a Common Metabolic Disease Often Resulting from Obesity 828

Insulin initiates a complex signal-transduction pathway in muscle 828

Metabolic syndrome often precedes type 2 diabetes 830

Excess fatty acids in muscle modify metabolism 830

Insulin resistance in muscle facilitates pancreatic failure 831

Metabolic derangements in type 1 diabetes result from insulin insufficiency and glucagon excess 832

27.4 Exercise Beneficially Alters the Biochemistry of Cells 833

Mitochondrial biogenesis is stimulated by muscular activity 834

Fuel choice during exercise is determined by the intensity and duration of activity 835

27.5 Food Intake and Starvation Induce Metabolic Changes 836

The starved-fed cycle is the physiological response to a fast 837

Metabolic adaptations in prolonged starvation minimize protein degradation 838

27.6 Ethanol Alters Energy Metabolism in the Liver 840

Ethanol metabolism leads to an excess of NADH 840

Excess ethanol consumption disrupts vitamin metabolism 842

Chapter 28 DNA Replication，Repair，and Recombination 849

28.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template 850

DNA polymerases require a template and a primer 850

All DNA polymerases have structural features in common 851

Two bound metal ions participate in the polymerase reaction 851

The specificity of replication is dictated by complementarity of shape between bases 852

An RNA primer synthesized by primase enables DNA synthesis to begin 853

One strand of DNA is made continuously，whereas the other strand is synthesized in fragments 853

DNA ligase joins ends of DNA in duplex regions 854

The separation of DNA strands requires specific helicases and ATP hydrolysis 854

28.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases 855

The linking number of DNA，a topological property，determines the degree of supercoiling 856

Topoisomerases prepare the double helix for unwinding 858

Type Ⅰ topoisomerases relax supercoiled structures 858

Type Ⅱ topoisomerases can introduce negative supercoils through coupling to ATP hydrolysis 859

28.3 DNA Replication Is Highly Coordinated 861

DNA replication requires highly processive polymerases 861

The leading and lagging strands are synthesized in a coordinated fashion 862

DNA replication in Escherichia coli begins at a unique site 864

DNA synthesis in eukaryotes is initiated at multiple sites 865

Telomeres are unique structures at the ends of linear chromosomes 866

Telomeres are replicated by telomerase，a specialized polymerase that carries its own RNA template 867

28.4 Many Types of DNA Damage Can Be Repaired 867

Eerrors can arise in DNA replication 867

Bases can be damaged by oxidizing agents，alkylating agents，and light 868

DNA damage can be detected and repaired by a variety of systems 869

The presence of thymine instead of uracil in DNA permits the repair of deaminated cytosine 871

Some genetic diseases are caused by the expansion of repeats of three nucleotides 872

Many cancers are caused by the defective repair of DNA 872

Many potential carcinogens can be detected by their mutagenic action on bacteria 873

28.5 DNA Recombination Plays Important Roles in Replication，Repair，and Other Processes 874

RecA can initiate recombination by promoting strand invasion 874

Some recombination reactions proceed through Holliday-junction intermediates 875

Chapter 29 RNA Synthesis and Processing 883

RNA synthesis comprises three stages：Initiation，elongation，and termination 884

29.1 RNA Polymerases Catalyze Transcription 885

RNA chains are formed de novo and grow in the 5’-to-3’ direction 886

RNA polymerases backtrack and correct errors 888

RNA polymerase binds to promoter sites on the DNA template to initiate transcription 888

Sigma subunits of RNA polymerase recognize promoter sites 889

RNA polymerases must unwind the template double helix for transcription to take place 890

Elongation takes place at transcription bubbles that move along the DNA template 890

Sequences within the newly transcribed RNA signal termination 891

Some messenger RNAs directly sense metabolite concentrations 892

The rho protein helps to terminate the transcription of some genes 892

Some antibiotics inhibit transcription 893

Precursors of transfer and ribosomal RNA are cleaved and chemically modified after transcription in prokaryotes 895

29.2 Transcription in Eukaryotes Is Highly Regulated 896

Three types of RNA polymerase synthesize RNA in eukaryotic cells 897

Three common elements can be found in the RNA polymerase Ⅱ promoter region 898

The TFIID protein complex initiates the assembly of the active transcription complex 899

Multiple transcription factors interact with eukaryotic promoters 900

Enhancer sequences can stimulate transcription at start sites thousands of bases away 900

29.3 The Transcription Products of Eukaryotic Polymerases Are Processed 901

RNA polymerase Ⅰ produces three ribosomal RNAs 901

RNA polymerase Ⅲ produces transfer RNA 902

The product of RNA polymerase Ⅱ，the pre-mRNA transcript，acquires a 5’ cap and a 3’ poly（A）tail 902

Small regulatory RNAs are cleaved from larger precursors 904

RNA editing changes the proteins encoded by mRNA 904

Sequences at the ends of introns specify splice sites in mRNA precursors 905

Splicing consists of two sequential transesterification reactions 906

Small nuclear RNAs in spliceosomes catalyze the splicing of mRNA precursors 907

Transcription and processing of mRNA are coupled 909

Mutations that affect pre-mRNA splicing cause disease 909

Most human pre-mRNAS can be spliced in alternative ways to yield different proteins 910

29.4 The Discovery of Catalytic RNA Was Revealing in Regard to Both Mechanism and Evolution 911

Chapter 30 Protein Synthesis 921

30.1 Protein Synthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences 922

The synthesis of long proteins requires a low error frequency 922

Transfer RNA molecules have a common design 923

Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing 925

30.2 Aminoacyl Transfer RNA Synthetases Read the Genetic Code 927

Amino acids are first activated by adenylation 927

Aminoacyl-tRNA synthetases have highly discriminating amino acid activation sites 928

Proofreading by aminoacyl-tRNA synthetases increases the fidelity of protein synthesis 929

Synthetases recognize various features of transfer RNA molecules 930

Aminoacyl-tRNA synthetases can be divided into two classes 931

30.3 The Ribosome Is the Site of Protein Synthesis 931

Ribosomal RNAs（5S，16S，and 23S rRNA）play a central role in protein synthesis 932

Ribosomes have three tRNA-binding sites that bridge the 30s and 50s subunits 934

The start signal is usually AUG preceded by several bases that pair with 16S rRNA 934

Bacterial protein synthesis is initiated by formylmethionyl transfer RNA 935

Formylmethionyl-tRNAf is placed in the P site of the ribosome in the formation of the 70S initiation complex 936

Elongation factors deliver aminoacyl-tRNA to the ribosome 936

Peptidyl transferase catalyzes peptide-bond synthesis 937

The formation of a peptide bond is followed by the GTP-driven translocation of tRNAs and mRNA 938

Protein synthesis is terminated by release factors that read stop codons 940

30.4 Eukaryotic Protein Synthesis Differs from Prokaryotic Protein Synthesis Primarily in Translation Initiation 941

Mutations in initiation factor 2 cause a curious pathological condition 942

30.5 A Variety of Antibiotics and Toxins Can Inhibit Protein Synthesis 943

Some antibiotics inhibit protein synthesis 943

Diphtheria toxin blocks protein synthesis in eukary