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Detailed Contents About the Authors v Preface vii Acknowledgments x Chapter 1 A Preview of the Cell The Cell Theory: A Brief History The Emergence of Modern Cell Biology The Cytological Strand Deals with Cellular Structure The Biochemical Strand Covers the Chemistry of Biological Structure and Function The Genetic Strand Focuses on Information Flow "Facts" and the Scientific Method Perspective Problem Set Suggested Reading Box 1A: Units of Measurement in Cell Biology Box 1B: Further Insights: Biology, "Facts," and the Scientific Method Chapter 2 The Chemistry of the Cell The Importance of Carbon Carbon-Containing Molecules Are Stable Carbon-Containing Molecules Are Diverse Carbon-Containing Molecules Can Form Stereoisomers The Importance of Water Water Molecules Are Polar Water Molecules Are Cohesive Water Has a High Temperature-Stabilizing Capacity Water Is an Excellent Solvent The Importance of Selectively Permeable Membranes A Membrane Is a Lipid Bilayer with Proteins Embedded in It Membranes Are Selectively Permeable The Importance of Synthesis by Polymerization Macromolecules Are Responsible for Most of the Form and Function in Living Systems Cells Contain Three Different Kinds of Macromolecules Macromolecules Are Synthesized by Stepwise Polymerization of Monomers The Importance of Self-Assembly Many Proteins Self-Assemble Molecular Chaperones Assist the Assembly of Some Proteins Noncovalent Interactions Are Important in the Folding of Macromolecules Self-Assembly Also Occurs in Other Cellular Structures The Tobacco Mosaic Virus Is a Case Study in Self-Assembly Self-Assembly Has Limits Hierarchical Assembly Provides Advantages for the Cell Perspective Problem Set Suggested Reading Box 2A: Further Insights: Tempus Fugit and the Fine Art of Watchmaking Chapter 3 The Macromolecules of the Cell Proteins The Monomers Are Amino Acids The Polymers Are Polypeptides and Proteins Several Kinds of Bonds and Interactions Are Important in Protein Folding and Stability Protein Structure Depends on Amino Acid Sequence and Interactions Nucleic Acids The Monomers Are Nucleotides The Polymers Are DNA and RNA A DNA Molecule Is a Double-Stranded Helix Polysaccharides The Monomers Are Monosaccharides The Polymers Are Storage and Structural Polysaccharides Polysaccharide Structure Depends on the Kinds of Glycosidic Bonds Involved Lipids Fatty Acids Are the Building Blocks of Several Classes of Lipids Triacylglycerols Are Storage Lipids Phospholipids Are Important in Membrane Structure Glycolipids Are Specialized Membrane Components Steroids Are Lipids with a Variety of Functions Terpenes Are Formed from Isoprene Perspective Problem Set Suggested Reading Box 3A: Further Insights: On the Trail of the Double Helix Chapter 4 Cells and Organelles Properties and Strategies of Cells All Organisms Are Prokaryotes, Eukaryotes, or Archaebacteria Cells Come in Many Sizes and Shapes Eukaryotic Cells Use Organelles to Compartmentalize Cellular Function Prokaryotes and Eukaryotes Differ from Each Other in Many Ways Cell Specialization Demonstrates the Unity and Diversity of Biology The Eukaryotic Cell in Overview: Pictures at an Exhibition The Plasma Membrane Defines Cell Boundaries and Retains Contents The Nucleus Is the Cell's Information Center Intracellular Membranes and Organelles Define Compartments The Cytoplasm of Eukaryotic Cells Contains the Cytosol and Cytoskeleton The Extracellular Matrix and the Cell Wall Are the "Outside" of the Cell Viruses, Viroids, and Prions: Agents That Invade Cells A Virus Consists of a DNA or RNA Core Surrounded by a Protein Coat Viroids Are Small, Circular RNA Molecules Prions Are "Proteinaceous Infective Particles" Perspective Problem Set Suggested Reading Box 4A: Human Applications: Organelles and Human Diseases Box 4B: Further Insights: Discovering Organelles: The Importance of Centrifuges and Chance Observations Chapter 5 Bioenergetics: The Flow of Energy in the Cell The Importance of Energy Cells Need Energy to Cause Six Different Kinds of Changes Most Organisms Obtain Energy Either from Sunlight or from Organic Food Molecules Energy Flows Through the Biosphere Continuously The Flow of Energy Through the Biosphere Is Accompanied by Flow of Matter Bioenergetics To Understand Energy Flow, We Need to Understand Systems, Heat, and Work The First Law of Thermodynamics Tells Us That Energy Is Conserved The Second Law of Thermodynamics Tells Us That Reactions Have Directionality Entropy and Free Energy Are Two Alternative Means of Assessing Thermodynamic Spontaneity Understanding _G The Equilibrium Constant Is a Measure of Directionality _G Can Be Calculated Readily The Standard Free Energy Change Is _G Measured Under Standard Conditions Summing Up: The Meaning of _G_ and _G°_ Free Energy Change: Sample Calculations Life and the Steady State: Reactions That Move Toward Equilibrium Without Ever Getting There Perspective Problem Set Suggested Reading Box 5A: Further Insights: Jumping Beans and Free Energy Chapter 6 Enzymes: The Catalysts of Life Activation Energy and the Metastable State Before a Chemical Reaction Can Occur, the Activation Energy Barrier Must Be Overcome The Metastable State Is a Result of the Activation Barrier Catalysts Overcome the Activation Energy Barrier Enzymes as Biological Catalysts Most Enzymes Are Proteins Substrate Binding, Activation, and Reaction Occur at the Active Site Enzyme Kinetics Most Enzymes Display Michaelis-Menten Kinetics What Is the Meaning of Vmax and Km? Why are Vmax and Km Important to Cell Biologists? The Double-Reciprocal Plot Is a Useful Means of Linearizing Kinetic Data Determining Km and Vmax: An Example Enzyme Inhibitors Act Irreversibly or Reversibly Enzyme Regulation Allosteric Enzymes Are Regulated by Molecules Other than Reactants and Products Allosteric Enzymes Exhibit Cooperative Interactions Between Subunits Enzymes Can Also Be Regulated by the Addition or Removal of Chemical Groups RNA Molecules as Enzymes: Ribozymes Perspective Problem Set Suggested Reading Box 6A: Further Insights: Monkeys and Peanuts Chapter 7 Membranes: Their Structure, Function, and Chemistry The Functions of Membranes Membranes Define Boundaries and Serve as Permeability Barriers Membranes Are Sites of Specific Proteins and Therefore of Specific Functions Membrane Proteins Regulate the Transport of Solutes Membrane Proteins Detect and Transmit Electrical and Chemical Signals Membrane Proteins Mediate Cell Adhesion and Cell-to-Cell Communication Models of Membrane Structure: An Experimental Perspective Overton and Langmuir: Lipids Are Important Components of Membranes Gorter and Grendel: The Basis of Membrane Structure Is a Lipid Bilayer Davson and Danielli: Membranes Also Contain Proteins Robertson: All Membranes Share a Common Underlying Structure Further Research Revealed Major Shortcomings of the Davson-Danielli Model Singer and Nicolson: A Membrane Consists of a Mosaic of Proteins in a Fluid Lipid Bilayer Unwin and Henderson: Most Membrane Proteins Contain Transmembrane Segments Recent Findings Further Refine Our Understanding of Membrane Structure Membrane Lipids: The "Fluid" Part of the Model Membranes Contain Several Major Classes of Lipids Thin-Layer Chromatography Is an Important Technique for Lipid Analysis Fatty Acids Are Essential to Membrane Structure and Function Membrane Asymmetry: Most Lipids Are Distributed Unequally Between the Two Monolayers The Lipid Bilayer Is Fluid Membranes Function Properly Only in the Fluid State Most Organisms Can Regulate Membrane Fluidity Lipid Rafts Are Localized Regions of Membrane Lipids That Are Involved in Cell Signaling Membrane Proteins: The "Mosaic" Part of the Model The Membrane Consists of a Mosaic of Proteins: Evidence from Freeze-Fracture Microscopy Membranes Contain Integral, Peripheral, and Lipid-Anchored Proteins Proteins Can Be Separated by SDS-Polyacrylamide Gel Electrophoresis Determining the Three-Dimensional Structure of Membrane Proteins Is Proving to Be Increasingly Feasible Molecular Biology Has Contributed Greatly to Our Understanding of Membrane Proteins Membrane Proteins Have a Variety of Functions Membrane Proteins Are Oriented Asymmetrically Across the Lipid Bilayer Many Membrane Proteins Are Glycosylated Membrane Proteins Vary in Their Mobility Perspective Problem Set Suggested Reading 193 Box 7A: Experimental Techniques: Revolutionizing the Study of Membrane Proteins: The Impact of Molecular Biology 182 Chapter 8 Transport Across Membranes: Overcoming the Permeability Barrier 195 Cells and Transport Processes 195 Solutes Cross Membranes by Simple Diffusion, Facilitated Diffusion, and Active Transport 196 The Movement of a Solute Across a Membrane Is Determined by Its Concentration Gradient or Its Electrochemical Potential 000 The Erythrocyte Plasma Membrane Provides Examples of Transport Mechanisms 197 Simple Diffusion: Unassisted Movement Down the Gradient 197 Diffusion Always Moves Solutes Toward Equilibrium 198 Osmosis Is the Diffusion of Water Across a Differentially Permeable Membrane 199 Simple Diffusion Is Limited to Small, Nonpolar Molecules 199 The Rate of Simple Diffusion Is Directly Proportional to the Concentration Gradient 201 Facilitated Diffusion: Protein-Mediated Movement Down the Gradient 203 Carrier Proteins and Channel Proteins Facilitate Diffusion by Different Mechanisms 203 Carrier Proteins Alternate Between Two Conformational States 203 Carrier Proteins Are Analogous to Enzymes in Their Specificity and Kinetics 204 Carrier Proteins Transport Either One or Two Solutes 204 The Erythrocyte Glucose Transporter and Anion Exchange Protein Are Examples of Carrier Proteins 204 Channel Proteins Facilitate Diffusion by Forming Hydrophilic Transmembrane Channels 206 Active Transport: Protein-Mediated Movement Up the Gradient 207 The Coupling of Active Transport to an Energy Source May Be Direct or Indirect 207 Direct Active Transport Depends on Four Types of Transport ATPases 208 Indirect Active Transport Is Driven by Ion Gradients 210 Examples of Active Transport 211 Direct Active Transport: The Na+/K+ Pump Maintains Electrochemical Ion Gradients 211 Indirect Active Transport: Sodium Symport Drives the Uptake of Glucose 214 The Bacteriorhodopsin Proton Pump Uses Light Energy to Transport Protons 215 The Energetics of Transport 218 For Uncharged Solutes, the _G of Transport Depends Only on the Concentration Gradient 218 For Charged Solutes, the _G of Transport Depends on the Electrochemical Potential 218 Beyond Ions and Small Molecules: Secretion and Uptake of Macromolecules and Particles 000 Perspective 220 Problem Set 221 Suggested Reading 224 Box 8A: Further Insights: Osmosis: The Special Case of Water Diffusion 200 Box 8B: Human Applications: Membrane Transport, Cystic Fibrosis, and the Prospects For Gene Therapy 212 Chapter 9 Chemotrophic Energy Metabolism: Glycolysis and Fermentation 368 Metabolic Pathways 368 ATP: The Universal Energy Coupler 369 ATP Contains Two Energy Rich Phosphoanhydride Bonds 369 ATP Hydrolysis Is Highly Exergonic Because of Charge Repulsion and Resonance Stabilization 370 ATP Is an Important Intermediate in Cellular Energy Transactions 371 Chemotrophic Energy Metabolism 373 Biological Oxidations Usually Involve the Removal of Both Electrons and Protons and Are Highly Exergonic 373 Coenzymes Such as NAD+ Serve as Electron Acceptors in Biological Oxidations 374 Most Chemotrophs Meet Their Energy Needsby Oxidizing Organic Food Molecules 375 Glucose Is One of the Most Important Oxidizable Substrates in Energy Metabolism 375 The Oxidation of Glucose Is Highly Exergonic 375 Glucose Catabolism Yields Much More Energyin the Presence of Oxygen than in Its Absence 375 Based on Their Need for Oxygen, Organisms Are Aerobic, Anaerobic, or Facultative 378 Glycolysis and Fermentation: ATP Generation Without the Involvement of Oxygen 378 Glycolysis Generates ATP by Catabolizing Glucose to Pyruvate 378 The Fate of Pyruvate Depends on Whether or Not Oxygen Is Available 383 In the Absence of Oxygen, Pyruvate Undergoes Fermentation to Regenerate NAD+ 384 Fermentation Taps Only a Small Fraction of the Free Energy of the Substrate but Conserves That Energy Efficiently as ATP 385 Alternative Substrates for Glycolysis 386 Other Sugars and Glycerol Are Also Catabolized by the Glycolytic Pathway 386 Polysaccharides Are Cleaved to Form Sugar Phosphates That Also Enter the Glycolytic Pathway 386 Gluconeogenesis 386 The Regulation of Glycolysis and Gluconeogenesis 389 Key Enzymes in the Glycolytic and Gluconeogenic Pathways Are Subject to Allosteric Regulation 390 Fructose-2,6-Bisphosphate Is an Important Regulator of Glycolysis and Gluconeogenesis 391 Perspective 393 Problem Set 394 Suggested Reading 397 Box 9A: Further Insights: "What Happens to the Sugar?" 376 Chapter 10 Chemotrophic Energy Metabolism: Aerobic Respiration 398 Cellular Respiration: Maximizing ATP Yields 398 Aerobic Respiration Yields Much More Energy than Fermentation 400 Respiration Includes Glycolysis, the TCA Cycle, Electron Transport, and ATP Synthesis 400 The Mitochondrion: Where the Action Takes Place 400 Mitochondria Are Often Present Where the ATP Needs Are Greatest 401 Are Mitochondria Interconnected Networks Rather than Discrete Organelles? 401 The Outer and Inner Membranes Define Two Separate Compartments 402 Mitochondrial Functions Occur in or on Specific Membranes and Compartments 404 In Prokaryotes, Respiratory Functions Are Localized to the Plasma Membrane and the Cytoplasm 404 The Tricarboxylic Acid Cycle: Oxidation in the Round 405 Pyruvate Is Converted to Acetyl Coenzyme A by Oxidative Decarboxylation 406 The TCA Cycle Begins with the Entry of Acetate as Acetyl CoA 406 NADH Is Formed and CO2 Is Released in Two Reactions of the TCA Cycle 406 Direct Generation of GTP (or ATP) Occurs at One Step in the TCA Cycle 409 The Final Oxidative Reactions of the TCA Cycle Generate FADH2 and NADH 409 Summing Up: The Products of the TCA Cycle are CO2, ATP, NADH, and FADH2 410 Several TCA Cycle Enzymes Are Subject to Allosteric Regulation 410 The TCA Cycle Also Plays a Central Role in the Catabolism of Fats and Proteins 412 The TCA Cycle Serves as a Source of Precursors for Anabolic Pathways 414 The Glyoxylate Cycle Converts Acetyl CoA to Carbohydrates 415 Electron Transport: Electron Flow from Coenzymes to Oxygen 415 The Electron Transport System Conveys Electrons Stepwise from Reduced Coenzymes to Oxygen 418 The Electron Transport System Consists of Five Different Kinds of Carriers 418 The Electron Carriers Function in a Sequence Determined by Their Reduction Potentials 420 Most of the Carriers Are Organized into Four Large Respiratory Complexes 422 The Respiratory Complexes Move Freely Within the Inner Membrane 424 The Electrochemical Proton Gradient: Key to Energy Coupling 425 Electron Transport and ATP Synthesis Are Coupled Events 426 The Chemiosmotic Model: The "Missing Link" Is a Proton Gradient 426 Coenzyme Oxidation Pumps Enough Protons to Form 3 ATP per NADH and 2 ATP per FADH2 427 The Chemiosmotic Model Is Affirmed by an Impressive Array of Evidence 427 1. Electron Transport Causes Protons to Be Pumped Out of the Mitochondrial Matrix 428 2. Components of the Electron Transport System Are Asymmetrically Oriented Within the Inner Mitochondrial Membrane 428 3. Membrane Vesicles Containing Complexes I, III, or IV Establish Proton Gradients 428 4. Oxidative Phosphorylation Requires a Membrane-Enclosed Compartment 429 5. Uncoupling Agents Abolish Both the Proton Gradient and ATP Synthesis 429 6. The Proton Gradient Has Enough Energy to Drive ATP Synthesis 429 7. Artificial Proton Gradients Can Drive ATP Synthesis in the Absence of Electron Transport 429 ATP Synthesis: Putting It All Together 430 F1 Particles Have ATP Synthase Activity 430 The FoF1 Complex: Proton Translocation Through Fo Drives ATP Synthesis by F1 431 ATP Synthesis by FoF1 Involves Physical Rotation of the Gamma Subunit 431 The Chemiosmotic Model Involves Dynamic Transmembrane Proton Traffic 434 Aerobic Respiration: Summing It All Up 434 The Maximum ATP Yield of Aerobic Respiration Is 36-38 ATPs per Glucose 435 Aerobic Respiration Is a Highly Efficient Process 438 Perspective 439 Problem Set 440 Suggested Reading 443 Box 10A: Further Insights: The Glyoxylate Cycle, Glyoxysomes, and Seed Germination 416 Chapter 11 Phototrophic Energy Metabolism: Photosynthesis 445 An Overview of Photosynthesis 445 The Chloroplast: A Photosynthetic Organelle 447 Chloroplasts Are Composed of Three Membrane Systems 448 Photosynthetic Energy Transduction 452 Chlorophyll Is Life's Primary Link to Sunlight 452 Accessory Pigments Further Expand Access to Solar Energy 453 Light-Gathering Molecules Are Organized into Photosystems and Light-Harvesting Complexes 453 Oxygenic Phototrophs Have Two Types of Photosystems 454 Photoreduction (NADPH Synthesis) in Oxygenic Phototrophs 455 Photosystem II Transfers Electrons from Water to a Plastoquinone 456 The Cytochrome b6/f Complex Transfers Electrons from a Plastoquinol to Plastocyanin 457 Photosystem I Transfers Electrons from Plastocyanin to Ferredoxin 458 Ferredoxin-NADP? Reductase Catalyzes the Reduction of NADP? 458 Photophosphorylation (ATP Synthesis) in Oxygenic Phototrophs 459 The ATP Synthase Complex Couples Transport of Protons Across the Thylakoid Membrane to ATP Synthesis 459 Cyclic Photophosphorylation Allows a Photosynthetic Cell to Balance NADPH and ATP Synthesis to Meet Its Precise Energy Needs 459 The Complete Energy Transduction System 460 A Photosynthetic Reaction Center from a Purple Bacterium 461 Photosynthetic Carbon Assimilation: The Calvin Cycle 462 Carbon Dioxide Enters the Calvin Cycle by Carboxylation of Ribulose-1,5-Bisphosphate 463 3-Phosphoglycerate Is Reduced to Form Glyceraldehyde-3-Phosphate 464 Regeneration of Ribulose-1,5-Bisphosphate Allows Continuous Carbon Assimilation 464 The Complete Calvin Cycle 465 The Calvin Cycle Is Highly Regulated to Ensure Maximum Efficiency 465 Rubisco Carbon Fixation Is Regulated by Rubisco Activase 000 Photosynthetic Energy Transduction and the Calvin Cycle 466 Carbohydrate Synthesis 467 Glyceraldehyde-3-Phosphate and Dihydroxyacetone Phosphate Are Combined to Form Glucose-1-Phosphate 467 The Biosynthesis of Sucrose Occurs in the Cytosol 468 The Biosynthesis of Starch Occurs in the Chloroplast Stroma 468 Other Photosynthetic Assimilation Pathways 468 Rubisco's Oxygenase Activity Decreases Photosynthetic Efficiency 468 The Glycolate Pathway Returns Reduced Carbon from Phosphoglycolate to the Calvin Cycle 469 C4 Plants Minimize Photorespiration by Confining Rubisco to Cells Containing High Concentrations of CO2 471 CAM Plants Minimize Photorespiration and Water Loss by Opening Their Stomata Only at Night 473 Perspective 474 Problem Set 475 Suggested Reading 477 Box 11A: Further Insights: The Endosymbiont Theory and the Evolution of Mitochondria and Chloroplasts from Ancient Bacteria 450 Chapter 12 Intracellular Compartments: The Endoplasmic Reticulum, Golgi Complex, Endosomes, Lysosomes, and Peroxisomes 323 The Endoplasmic Reticulum 323 The Two Basic Kinds of Endoplasmic Reticulum Differ in Structure and Function 324 Rough ER Is Involved in the Biosynthesis and Processing of Proteins 325 Smooth ER Is Involved in Drug Detoxification, Carbohydrate Metabolism, and Other Cellular Processes 330 The ER Plays a Central Role in the Biosynthesis of Membranes 332 The Golgi Complex 333 The Golgi Complex Consists of a Series of Membrane-Bounded Cisternae 333 Two Models Depict the Flow of Lipids and Proteins Through the Golgi Complex 335 Roles of the ER and Golgi Complex in Protein Glycosylation 336 Roles of the ER and Golgi Complex in Protein Trafficking 338 ER-Specific Proteins Contain Retrieval Tags 338 Golgi Complex Proteins May Be Sorted According to the Lengths of Their Membrane-Spanning Domains 339 Targeting of Soluble Lysosomal Proteins to Endosomes and Lysosomes Is a Model for Protein Sorting in the TGN 339 Secretory Pathways Transport Molecules to the Exterior of the Cell 341 Exocytosis and Endocytosis: Transporting Material Across the Plasma Membrane 342 Exocytosis Releases Intracellular Molecules to the Extracellular Medium 342 Endocytosis Imports Extracellular Molecules by Forming Vesicles from the Plasma Membrane 343 Coated Vesicles in Cellular Transport Processes 349 Clathrin-Coated Vesicles Are Surrounded by Lattices Composed of Clathrin and Adaptor Protein 349 The Assembly of Clathrin Coats Drives the Formation of Vesicles from the Plasma Membrane and TGN 350 COPI- and COPII-Coated Vesicles Connect the ER and Golgi Complex Cisternae 351 SNARE Proteins Mediate Fusion of Vesicles and Target Membranes Following Tethering 352 Lysosomes and Cellular Digestion 353 Lysosomes Isolate Digestive Enzymes from the Rest of the Cell 353 Lysosomes Develop from Endosomes 354 Lysosomal Enzymes Are Important for Several Different Digestive Processes 355 Lysosomal Storage Diseases Are Usually Characterized by the Accumulation of Indigestible Material 357 The Plant Vacuole: A Multifunctional Organelle 357 Peroxisomes 358 The Discovery of Peroxisomes Depended on Innovations in Equilibrium Density Centrifugation 358 Most Peroxisomal Functions Are Linked to Hydrogen Peroxide Metabolism 359 Plant Cells Contain Types of Peroxisomes Not Found in Animal Cells 361 Peroxisome Biogenesis Occurs by Division of Preexisting Peroxisomes 362 Perspective 363 Problem Set 365 Suggested Reading 367 Box 12A: Experimental Techniques: Centrifugation: An Indispensable Technique of Cell Biology 326 Box 12B: Human Applications: Cholesterol, the LDL Receptor, and Receptor-Mediated Endocytosis 346 Chapter 13 Signal Transduction Mechanisms: I. Electrical Signals in Nerve Cells 225 The Nervous System 225 Neurons Are Specially Adapted for the Transmission of Electrical Signals 227 Understanding Membrane Potential 228 The Resting Membrane Potential Depends on Differing Concentrations of Ions Inside and Outside the Neuron 228 The Nernst Equation Describes the Relationship Between Membrane Potential and Ion Concentration 230 Ions Trapped Inside the Cell Have Important Effects on Resting Membrane Potential 230 Steady-State Concentrations of Common Ions Affect Resting Membrane Potential 230 The Goldman Equation Describes the Combined Effects of Ions on Membrane Potential 231 Electrical Excitability 233 Ion Channels Act Like Gates for the Movement of Ions Through the Membrane 233 Patch Clamping and Molecular Biological Techniques Allow the Activity of Single Ion Channels to Be Monitored 233 Specific Domains of Voltage-Gated Channels Act as Sensors and Inactivators 234 The Action Potential 236 Action Potentials Propagate Electrical Signals Along an Axon 236 Action Potentials Involve Rapid Changes in the Membrane Potential of the Axon 236 Action Potentials Result from the Rapid Movement of Ions Through Axonal Membrane Channels 237 Action Potentials Are Propagated Along the Axon Without Losing Strength 240 The Myelin Sheath Acts Like an Electrical Insulator Surrounding the Axon 241 Synaptic Transmission 243 Neurotransmitters Relay Signals Across Nerve Synapses 243 Elevated Calcium Levels Stimulate Secretion of Neurotransmitters from Presynaptic Neurons 245 Secretion of Neurotransmitters Requires the Docking and Fusion of Vesicles with the Plasma Membrane 246 Neurotransmitters Are Detected by Specific Receptors on Postsynaptic Neurons 247 Neurotransmitters Must Be Inactivated Shortly After Their Release 249 Integration and Processing of Nerve Signals 250 Neurons Can Integrate Signals from Other Neurons Through Both Temporal and Spatial Summation 251 Neurons Can Integrate Both Excitatory and Inhibitory Signals from Other Neurons 251 Perspective 252 Problem Set 254 Suggested Reading 255 Box 13A: Human Applications: Poisoned Arrows, Snake Bites, and Nerve Gases 250 Chapter 14 Signal Transduction Mechanisms: II. Messengers and Receptors 256 Chemical Signals and Cellular Receptors 256 Different Types of Chemical Signals Can Be Received by Cells 257 Receptor Binding Involves Specific Interactions Between Ligands and Their Receptors 257 Receptor Binding Activates a Sequence of Signal Transduction Events Within the Cell 258 G Protein-Linked Receptors 259 Seven-Membrane Spanning Receptors Act via G Proteins 259 Cyclic AMP Is a Second Messenger Used by One Class of G Proteins 261 Disruption of G Protein Signaling Causes Several Human Diseases 262 Many G Proteins Use Inositol Trisphosphate and Diacylglycerol as Second Messengers 263 The Release of Calcium Ions Is a Key Event in Many Signaling Processes 264 Nitric Oxide Couples G Protein-Linked Receptor Stimulation in Endothelial Cells to Relaxation of Smooth Muscle Cells in Blood Vessels 269 Protein Kinase-Associated Receptors 270 Receptor Tyrosine Kinases Aggregate and Undergo Autophosphorylation 270 Receptor Tyrosine Kinases Initiate a Signal Transduction Cascade Involving Ras and MAP Kinase 271 Receptor Tyrosine Kinases Activate a Variety of Other Signaling Pathways 272 Growth Factors as Messengers 272 Disruption of Growth Factor Signaling Through Receptor Tyrosine Kinases Can Have Dramatic Effects on Embryonic Development 273 Other Growth Factors Transduce Their Signals via Receptor Serine/Threonine Kinases 274 Growth Factor Receptor Pathways Share Common Themes 275 Disruption of Growth Factor Signaling Can Lead to Cancer 275 The Endocrine and Paracrine Hormone Systems 276 Hormonal Signals Can Be Classified by the Distance They Travel to Their Target Cells 276 Hormones Control Many Physiological Functions 276 Animal Hormones Can Be Classified by Their Chemical Properties 276 Adrenergic Hormones and Receptors Are a Good Example of Endocrine Regulation 278 Prostaglandins Are a Good Example of Paracrine Regulation 280 Cell Signals and Apoptosis 282 Apoptosis Is Triggered by Death Signals or Withdrawal of Survival Factors 284 Perspective 286 Problem Set 287 Suggested Reading 288 Box 14A: Experimental Techniques: Using Genetic Model Systems to Study Cell Signaling 000 Chapter 15 Cytoskeletal Systems 742 The Major Structural Elements of the Cytoskeleton 742 Techniques for Studying the Cytoskeleton 744 Modern Microscopy Techniques Have Revolutionized the Study of the Cytoskeleton 744 Drugs and Mutations Can Be Used to Disrupt Cytoskeletal Structures 744 Microtubules 744 Two Types of Microtubules Are Responsible for Many Functions in the Cell 744 Tubulin Heterodimers Are the Protein Building Blocks of Microtubules 746 Microtubules Form by the Addition of Tubulin Dimers at Their Ends 747 Addition of Tubulin Dimers Occurs More Quickly at the Plus Ends of Microtubules 747 GTP Hydrolysis Contributes to the Dynamic Instability of Microtubules 748 MTs Originate from Microtubule-Organizing Centers Within the Cell 749 MTOCs Organize and Polarize the Microtubules Within Cells 750 Microtubule Stability Within Cells Is Highly Regulated 751 Drugs Can Affect the Assembly of Microtubules 753 Microtubules Are Regulated Along Their Length by Microtubule-Associated Proteins (MAPs) 753 Microfilaments 754 Actin Is the Protein Building Block of Microfilaments 755 Different Types of Actin and Actin-Related Proteins Are Found in Cells 756 G-Actin Monomers Polymerize into F-Actin Microfilaments 756 Cells Can Dynamically Regulate How and Where Actin Is Assembled 757 Specific Proteins and Drugs Affect Polymer Dynamics at the Ends of Microfilaments 758 Inositol Phospholipids Regulate Molecules That Affect Actin Polymerization 758 Actin Branching Is Controlled by the Arp2/3 Complex 000 Rho, Rac, and Cdc42 Regulate Actin Polymerization 000 Actin-Binding Proteins Regulate Interactions Between Microfilaments 758 Bundled Actin Filaments Form the Core of Microvilli 000 A Variety of Proteins Link Actin to Membranes 760 Intermediate Filaments 762 Intermediate Filament Proteins Are Tissue-Specific 762 Intermediate Filaments Assemble from Fibrous Subunits 763 Intermediate Filaments Confer Mechanical Strength on Tissues 764 The Cytoskeleton Is a Mechanically Integrated Structure 765 Perspective 765 Problem Set 766 Suggested Reading 767 Box 15A: Human Applications; Infectious Microorganisms Can Move Within Cells Using Actin "Tails" 000 Chapter 16 Cellular Movement: Motility and Contractility 769 Motile Systems 769 Intracellular Microtubule-Based Movement: Kinesin and Dynein 770 Motor MAPs Move Organelles Along Microtubules During Axonal Transport 770 Kinesins Move Along Microtubules by Hydrolyzing ATP 771 Kinesins Are a Large Family of Proteins with Varying Structures and Functions 772 Dyneins Can Be Grouped into Two Major Classes: Axonemal and Cytoplasmic Dyneins 772 Motor MAPs Are Involved in the Transport of Intracellular Vesicles 773 Microtubule-Based Motility 773 Cilia and Flagella Are Common Motile Appendages of Eukaryotic Cells 773 Cilia and Flagella Consist of an Axoneme Connected to a Basal Body 774 Microtubule Sliding Within the Axoneme Causes Cilia and Flagella to Bend 776 Actin-Based Cell Movement: The Myosins 777 Myosins Have Diverse Roles in Cell Motility 777 Some Myosins Move Along Actin Filaments in Short Steps 779 Filament-Based Movement in Muscle 779 Skeletal Muscle Cells Are Made of Thin and Thick Filaments 779 Sarcomeres Contain Ordered Arrays of Actin, Myosin, and Accessory Proteins 780 The Sliding-Filament Model Explains Muscle Contraction 782 Cross-Bridges Hold Filaments Together and ATP Powers Their Movement 783 The Regulation of Muscle Contraction Depends on Calcium 786 The Coordinated Contraction of Cardiac Muscle Cells Involves Electrical Coupling 789 Smooth Muscle Is More Similar to Nonmuscle Cells than to Skeletal Muscle 790 Actin-Based Motility in Nonmuscle Cells 792 Cell Migration via Lamellipodia Involves Cycles of Protrusion, Attachment, Translocation, and Detachment 792 Amoeboid Movement Involves Cycles of Gelation and Solation of the Actin Cytoskeleton 795 Cytoplasmic Streaming Moves Components Within the Cytoplasm of Some Cells 795 Chemotaxis Is a Directional Movement in Response to a Graded Chemical Stimulus 798 Perspective 799 Problem Set 800 Suggested Reading 801 Box 16A: Human Applications: Cytoskeletal Motor Proteins and Human Disease 778 Chapter 17 Beyond the Cell: Extracellular Structures, Cell Adhesion, and Cell Junctions 290 The Extracellular Matrix of Animal Cells 290 Collagens Are Responsible for the Strength of the Extracellular Matrix 291 A Precursor Called Procollagen Forms Many Types of Tissue-Specific Collagens 292 Elastins Impart Elasticity and Flexibility to the Extracellular Matrix 293 Collagen and Elastin Fibers Are Embedded in a Matrix of Proteoglycans 294 Free Hyaluronate Lubricates Joints and Facilitates Cell Migration 294 Proteoglycans and Adhesive Glycoproteins Anchor Cells to the Extracellular Matrix 295 Fibronectins Bind Cells to the ECM and Guide Cellular Movement 296 Laminins Bind Cells to the Basal Lamina 297 Integrins Are Cell Surface Receptors that Bind ECM Constituents 298 The Glycocalyx Is a Carbohydrate-Rich Zone at the Periphery of Animal Cells 302 Cell-Cell Recognition and Adhesion 302 Transmembrane Proteins Mediate Cell-Cell Adhesion 302 Carbohydrate Groups Are Important in Cell-Cell Recognition and Adhesion 304 Cell Junctions 306 Adhesive Junctions Link Adjoining Cells to Each Other 306 Tight Junctions Prevent the Movement of Molecules Across Cell Layers 310 Gap Junctions Allow Direct Electrical and Chemical Communication Between Cells 313 The Plant Cell Surface 314 Cell Walls Provide a Structural Framework and Serve as a Permeability Barrier 314 The Plant Cell Wall Is a Network of Cellulose Microfibrils, Polysaccharides, and Glycoproteins 315 Cell Walls Are Synthesized in Several Discrete Stages 316 Plasmodesmata Permit Direct Cell-Cell Communication Through the Cell Wall 318 Perspective 319 Problem Set 320 Suggested Reading 322 Box 17A: Human Applications: Food Poisoning and "Bad Bugs": The Cell Surface Connection 308 Chapter 18 The Structural Basis of Cellular Information: DNA, Chromosomes, and the Nucleus 479 The Chemical Nature of the Genetic Material 479 Miescher's Discovery of DNA Led to Conflicting Proposals Concerning the Chemical Nature of Genes 480 Avery Showed That DNA Is the Genetic Material of Bacteria 481 Hershey and Chase Showed That DNA Is the Genetic Material of Viruses 482 Chargaff's Rules Reveal That A=T and G=C 486 DNA Structure 486 Watson and Crick Discovered That DNA Is a Double Helix 487 DNA Can Be Interconverted Between Relaxed and Supercoiled Forms 489 The Two Strands of a DNA Double Helix Can Be Separated by Denaturation and Rejoined by Renaturation 490 The Organization of DNA in Genomes 491 Genome Size Generally Increases with an Organism's Complexity 492 Restriction Enzymes Cleave DNA Molecules at Specific Sites 492 Rapid Procedures Exist for DNA Sequencing 496 The Genomes of Numerous Organisms Have Been Sequenced 497 The Field of Bioinformatics Has Emerged to Decipher Genomes and Proteomes 498 Repeated DNA Sequences Partially Explain the Large Size of Eukaryotic Genomes 499 DNA Packaging 501 Prokaryotes Package DNA in Bacterial Chromosomes and Plasmids 501 Eukaryotes Package DNA in Chromatin and Chromosomes 504 Nucleosomes Are the Basic Unit of Chromatin Structure 505 A Histone Octamer Forms the Nucleosome Core 506 Nucleosomes Are Packed Together to Form Chromatin Fibers and Chromosomes 506 Eukaryotes Also Package Some of Their DNA in Mitochondria and Chloroplasts 507 The Nucleus 510 A Double-Membrane Nuclear Envelope Surrounds the Nucleus 510 Molecules Enter and Exit the Nucleus Through Nuclear Pores 513 The Nuclear Matrix and Nuclear Lamina Are Supporting Structures of the Nucleus 515 Chromatin Fibers Are Dispersed Within the Nucleus in a Nonrandom Fashion 516 The Nucleolus Is Involved in Ribosome Formation 517 Perspective 518 Key Terms for Self-Testing 519 Problem Set 520 Suggested Reading 522 Box 18A: Further Insights: Phages: Model Systems for Studying Genes 484 Box 18B: Further Insights: A Closer Look at Restriction Enzymes 494 Box 18C: Experimental Techniques: DNA Fingerprinting 502 Chapter 19 The Cell Cycle, DNA Replication, and Mitosis 523 An Overview of the Cell Cycle 523 DNA Replication 525 Equilibrium Density Centrifugation Shows That DNA Replication Is Semiconservative 525 DNA Replication Is Usually Bidirectional 527 Eukaryotic DNA Replication Involves Multiple Replicons 528 DNA Polymerases Catalyze the Elongation of DNA Chains 530 DNA Is Synthesized as Discontinuous Segments That Are Joined Together by DNA Ligase 532 Proofreading Is Performed by the 3__5_ Exonuclease Activity of DNA Polymerase 535 RNA Primers Initiate DNA Replication 535 Unwinding the DNA Double Helix Requires DNA Helicases, Topoisomerases, and Single-Stranded DNA Binding Proteins 536 Putting It All Together: DNA Replication in Summary 537 Telomeres Solve the DNA End-Replication Problem 539 Eukaryotic DNA Is Licensed for Replication 541 DNA Damage and Repair 541 DNA Damage Can Occur Spontaneously or in Response to Mutagens 541 Translesion Synthesis and Excision Repair Correct Mutations Involving Abnormal Nucleotides 543 Mismatch Repair Corrects Mutations That Involve Noncomplementary Base Pairs 543 Damage Repair Helps Explain Why DNA Contains Thymine Instead of Uracil 544 Double-Strand DNA Breaks Are Repaired by Nonhomologous End-Joining or Homologous Recombination 000 Nuclear and Cell Division 544 Mitosis Is Subdivided into Prophase, Prometaphase, Metaphase, Anaphase, and Telophase 544 The Mitotic Spindle Is Responsible for Chromosome Movements During Mitosis 549 Cytokinesis Divides the Cytoplasm 551 Regulation of the Cell Cycle 554 The Length of the Cell Cycle Varies Among Different Cell Types 554 Progression Through the Cell Cycle Is Controlled at Several Key Transition Points 555 Studies Involving Cell Fusion and Cell Cycle Mutants Led to the Identification of Molecules That Control the Cell Cycle 556 Progression Through the Cell Cycle Is Controlled by Cyclin-Dependent Kinases (Cdks) 000 Mitotic Cdk-Cyclin Drives Progression Through the G2-M Transition by Phosphorylating Key Proteins Involved in the Early Stages of Mitosis 000 Mitotic Cdk-Cyclin Contributes to Activation of the Anaphase-Promoting Complex 000 G1 Cdk-Cyclin Regulates Progression Through the Restriction Point by Phosphorylating the Rb Protein 000 Checkpoint Pathways Monitor for Chromosome-to-Spindle Attachments, Completion of DNA Replication, and DNA Damage 000 Putting It All Together: The Cell Cycle Regulation Machine 562 Growth Factors and Cell Proliferation 562 Stimulatory Growth Factors Activate the Ras Pathway 562 Inhibitory Growth Factors Act Through Cdk Inhibitors 564 Stimulatory Growth Factors Can Also Activate the P13K-Akt Pathway 000 Perspective 571 Problem Set 573 Suggested Reading 576 Box 19A: Experimental Techniques: The PCR Revolution 533 Chapter 20 Sexual Reproduction, Meiosis, and Genetic Recombination 577 Sexual Reproduction 577 Sexual Reproduction Produces Genetic Variety by Bringing Together Chromosomes from Two Different Parents 577 Diploid Cells May Be Homozygous or Heterozygous for Each Gene 578 Gametes Are Haploid Cells Specialized for Sexual Reproduction 579 Meiosis 580 The Life Cycles of Sexual Organisms Have Diploid and Haploid Phases 580 Meiosis Converts One Diploid Cell into Four Haploid Cells 581 Meiosis I Produces Two Haploid Cells That Have Chromosomes Composed of Sister Chromatids 582 Meiosis II Resembles a Mitotic Division 588 Sperm and Egg Cells Are Generated by Meiosis Accompanied by Cell Differentiation 588 Meiosis Generates Genetic Diversity 590 Genetic Variability: Segregation and Assortment of Alleles 590 Information Specifying Recessive Traits Can Be Present Without Being Displayed 590 The Law of Segregation States That the Alleles of Each Gene Separate from Each Other During Gamete Formation 592 The Law of Independent Assortment States That the Alleles of Each Gene Separate Independently of the Alleles of Other Genes 592 Early Microscopic Evidence Suggested That Chromosomes Might Carry Genetic Information 593 Chromosome Behavior Explains the Laws of Segregation and Independent Assortment 593 The DNA Molecules of Homologous Chromosomes Have Similar Base Sequences 594 Genetic Variability: Recombination and Crossing Over 595 Chromosomes Contain Groups of Linked Genes That Are Usually Inherited Together 596 Homologous Chromosomes Exchange Segments During Crossing Over 597 Gene Locations Can Be Mapped by Measuring Recombination Frequencies 597 Genetic Recombination in Bacteria and Viruses 598 Co-infection of Bacterial Cells with Related Bacteriophages Can Lead to Genetic Recombination 598 Transformation and Transduction Involve Recombination with Free DNA or DNA Brought into Bacterial Cells by Bacteriophages 599 Conjugation Is a Modified Sexual Activity That Facilitates Genetic Recombination in Bacteria 600 Molecular Mechanism of Homologous Recombination 602 DNA Breakage-and-Exchange Underlies Homologous Recombination 602 Homologous Recombination Can Lead to Gene Conversion 603 Homologous Recombination Is Initiated by Single-Strand DNA Exchanges (Holliday Junctions) 604 The Synaptonemal Complex Facilitates Homologous Recombination During Meiosis 606 Recombinant DNA Technology and Gene Cloning 606 The Discovery of Restriction Enzymes Paved the Way for Recombinant DNA Technology 607 DNA Cloning Techniques Permit Individual Gene Sequences to Be Produced in Large Quantities 608 Genomic and cDNA Libraries Are Both Useful for DNA Cloning 612 Large DNA Segments Can Be Cloned in YACs and BACs 613 Genetic Engineering 614 Genetic Engineering Can Produce Valuable Proteins That Are Otherwise Difficult to Obtain 614 The Ti Plsmid Is a Useful Vector for Introducing Foreign Genes into Plants 614 Genetic Modification Can Improve the Traits of Food Crops 615 Concerns Have Been Raised About the Safety and Environmental Risks of GM Crops 616 Gene Therapies Are Being Developed for the Treatment of Human Diseases 616 Perspective 618 Problem Set 619 Suggested Reading 621 Box 20A: Experimental Techniques: Supermouse, an Early Transgenic Triumph 617 Chapter 21 Gene Expression: I. The Genetic Code and Transcription 623 The Directional Flow of Genetic Information 623 The Genetic Code 624 Experiments on Neurospora Revealed That Genes Can Code for Enzymes 624 Most Genes Code for the Amino Acid Sequences of Polypeptide Chains 625 The Genetic Code Is a Triplet Code 628 The Genetic Code Is Degenerate and Nonoverlapping 631 Messenger RNA Guides the Synthesis of Polypeptide Chains 632 The Codon Dictionary Was Established Using Synthetic RNA Polymers and Triplets 633 Of the 64 Possible Codons in Messenger RNA, 61 Code for Amino Acids 634 The Genetic Code Is (Nearly) Universal 634 Transcription in Prokaryotic Cells 635 Transcription Is Catalyzed by RNA Polymerase, Which Synthesizes RNA Using DNA as a Template 635 Transcription Involves Four Stages: Binding, Initiation, Elongation, and Termination 635 Transcription in Eukaryotic Cells 640 RNA Polymerases I, II, and III Carry Out Transcription in the Eukaryotic Nucleus 640 Three Classes of Promoters Are Found in Eukaryotic Nuclear Genes, One for Each Type of RNA Polymerase 641 General Transcription Factors Are Involved in the Transcription of All Nuclear Genes 643 Elongation, Termination, and RNA Cleavage Are Involved in Completing Eukaryotic RNA Synthesis 644 RNA Processing 644 Ribosomal RNA Processing Involves Cleavage of Multiple rRNAs from a Common Precursor 644 Transfer RNA Processing Involves Removal, Addition, and Chemical Modification of Nucleotides 646 Messenger RNA Processing in Eukaryotes Involves Capping, Addition of Poly(A), and Removal of Introns 647 Spliceosomes Remove Introns from Pre-mRNA 650 Some Introns Are Self-Splicing 651 Why Do Eukaryotic Genes Have Introns? 652 RNA Editing Allows the Coding Sequence of mRNA to Be Altered 653 Key Aspects of mRNA Metabolism 654 Most mRNA Molecules Have a Relatively Short Life Span 655 The Existence of mRNA Allows Amplification of Genetic Information 655 Perspective 655 Problem Set 656 Suggested Reading 658 Box 21A: Further Insights: Reverse Transcription, Retroviruses, and Retrotransposons 626 Box 21B: Experimental Techniques: Identifying Protein-Binding Sites on DNA 638 Chapter 22 Gene Expression: II. Protein Synthesis and Sorting 660 Translation: The Cast of Characters 660 The Ribosome Carries Out Polypeptide Synthesis 660 Transfer RNA Molecules Bring Amino Acids to the Ribosome 662 Aminoacyl-tRNA Synthetases Link Amino Acids to the Correct Transfer RNAs 664 Messenger RNA Brings Polypeptide-Coding Information to the Ribosome 666 Protein Factors Are Required for the Initiation, Elongation, and Termination of Polypeptide Chains 666 The Mechanism of Translation 666 The Initiation of Translation Requires Initiation Factors, Ribosomal Subunits, mRNA, and Initiator tRNA 667 Chain Elongation Involves Sequential Cycles of Aminoacyl tRNA Binding, Peptide Bond Formation, and Translocation 669 Termination of Polypeptide Synthesis Is Triggered by Release Factors That Recognize Stop Codons 671 Polypeptide Folding Is Facilitated by Molecular Chaperones 672 Protein Synthesis Typically Utilizes a Substantial Fraction of a Cell's Energy Budget 672 A Summary of Translation 674 Mutations and Translation 674 Suppressor tRNAs Overcome the Effects of Some Mutations 000 Nonsense-Mediated Decay and Nonstop Decay Are Mechanisms for Promoting the Destruction of Defective mRNAs 000 Posttranslational Processing 675 Protein Targeting and Sorting 676 Cotranslational Import Allows Some Polypeptides to Enter the ER as They Are Being Synthesized 678 Posttranslational Import Allows Some Polypeptides to Enter Organelles After They Have Been Synthesized 683 Perspective 688 Problem Set 689 Suggested Reading 691 Box 22A: Human Applications: Protein-Folding Diseases 673 Box 22B: Further Insights: A Mutation Primer 676 Chapter 23 The Regulation of Gene Expression 692 Gene Regulation in Prokaryotes 692 Catabolic and Anabolic Pathways Are Regulated Through Induction and Repression Respectively 692 The Genes Involved in Lactose Catabolism Are Organized into an Inducible Operon 694 The lac Repressor Is an Allosteric Protein Whose Binding to DNA Is Controlled by Lactose 694 Studies of Mutant Bacteria Revealed How the lac Operon Is Organized 000 The Genes Involved in Tryptophan Synthesis Are Organized into a Repressible Operon 698 The lac and trp Operons Illustrate the Negative Control of Transcription 700 Catabolite Repression Illustrates the Positive Control of Transcription 700 Inducible Operons Are Often Under Dual Control 700 Sigma Factors Determine Which Sets of Genes Can Be Expressed 701 Attenuation Allows Transcription to Be Regulated After the Initiation Step 701 Riboswitches Allow Transcription and Translation to Be Controlled by Small Molecule Interactions with RNA 000 Eukaryotic Gene Regulation: Genomic Control 000 Multicellular Eukaryotes Are Composed of Numerous Specialized Cell Types 000 Eukaryotic Gene Expression Is Regulated at Five Main Levels 000 As a General Rule, the Cells of a Multicellular Organism All Contain the Same Set of Genes 000 Gene Amplification and Deletion Can Alter the Genome 707 DNA Rearrangements Can Alter the Genome 709 Chromosome Puffs Provide Visual Evidence That Chromatin Decondensation Is Involved in Genomic Control 710 DNase I Sensitivity Provides Further Evidence for the Role of Chromatin Decondensation in Genomic Control 712 DNA Methylation Is Associated with Inactive Regions of the Genome 714 Changes in Histones, HMG Proteins, and the Nuclear Matrix Are Associated with Active Regions of the Genome 715 Eukaryotic Gene Regulation: Transcriptional Control 715 Different Sets of Genes are Transcribed in Different Cell Types 715 DNA Microarrays Allow the Expression of Thousands of Genes to Be Monitored Simultaneously 716 Proximal Control Elements Lie Close to the Promoter 717 Enhancers and Silencers Are Located at Variable Distances from the Promoter 718 Coactivators Mediate the Interaction Between Regulatory Transcription Factors and the RNA Polymerase Complex 719 Multiple DNA Control Elements and Transcription Factors Act in Combination 721 Several Common Structural Motifs Allow Regulatory Transcription Factors to Bind to DNA and Activate Transcription 721 DNA Response Elements Coordinate the Expression of Nonadjacent Genes 724 Steroid Hormone Receptors Are Transcription Factors That Bind to Hormone Response Elements 724 CREBs and STATs are Examples of Transcription Factors Activated by Phosphorylation 725 The Heat-Shock Response Element Coordinates the Expression of Genes Activated by Elevated Temperatures 726 Homeotic Genes Code for Transcription Factors That Regulate Embryonic Development 727 Eukaryotic Gene Regulation: Posttranscriptional Control 728 Control of RNA Processing and Nuclear Export Follows Transcription 728 Translation Rates Can Be Controlled by Initiation Factors and Translational Repressors 730 Translation Can Also Be Controlled by Regulation of mRNA Half-Life 731 RNA Interference Utilizes Short RNAs to Silence the Expression of Genes Containing Complementary Base Sequences 000 MicroRNAs Produced by Normal Cellular Genes Silence the Translation of Developmentally Important Messenger RNAs 000 Posttranslational Control Involves Modifications of Protein Structure, Function, and Degradation 732 Ubiquitin Targets Proteins for Degradation by Proteasomes 733 A Summary of Eukaryotic Gene Regulation 734 Perspective 736 Problem Set 738 Suggested Reading 741 Box 23A: Further Insights: Dolly: A Lamb with No Father 708 Chapter 24 Cancer Cells 000 Uncontrolled Cell Proliferation 000 Tumors Are Produced by Uncontrolled Cell Proliferation in Which the Balance Between Cell Division and Cell Differentiation Is Disrupted 3 Cancer Cell Proliferation Is Anchorage-Independent and Insensitive to Population Density 4 Cancer Cells Are Immortalized by Mechanisms That Maintain Telomere Length 5 Abnormalities in Signaling Pathways, Cell Cycle Controls, and Apoptosis Contribute to Uncontrolled Proliferation 6 How Cancer Spreads 7 Angiogenesis Is Required for Tumors To Grow Beyond a Few Millimeters in Diameter 7 Blood Vessel Growth Is Controlled by a Balance Between Angiogenesis Activators and Inhibitors 8 Spreading of Cancer by Invasion and Metastasis Is a Complex Multistep Process 9 Changes in Cell Adhesion, Motility, and Protease Production Allow Cancer Cells to Invade Surrounding Tissues and Vessels 10 Relatively Few Cancer Cells Survive the Voyage Through the Bloodstream and Establish Metastases 11 Blood-Flow Patterns and Organ-Specific Factors Determine Where Cancer Cells Metastasize 12 The Immune System Can Inhibit the Development of Metastases 13 What Causes Cancer? 15 Epidemiological Data Have Allowed Many Causes of Cancer To Be Identified 15 Many Chemicals Can Cause Cancer, Often After Metabolic Activation in the Liver 16 DNA Mutations Triggered by Chemical Carcinogens Lead to Cancer 17 Cancer Arises Through a Multistep Process Involving Initiation, Promotion, and Tumor Progression 17 Ionizing and Ultraviolet Radiation Also Cause DNA Mutations That Lead to Cancer 19 Viruses and Other Infectious Agents Are Responsible for Some Cancers 20 Oncogenes and Tumor Suppressor Genes 22 Oncogenes Are Genes Whose Presence Can Trigger the Development of Cancer 22 Proto-oncogenes Are Converted into Oncogenes by Several Distinct Mechanisms 24 Most Oncogenes Code for Components of Growth Signaling Pathways 26 Tumor Suppressor Genes Are Genes Whose Loss or Inactivation Can Lead to Cancer 29 The RB Tumor Suppressor Gene Was Discovered by Studying Families with Hereditary Retinoblastoma 31 The p53 Tumor Suppressor Gene Is the Most Frequently Mutated Gene in Human Cancers 32 The APC Tumor Suppressor Gene Codes for a Protein That Inhibits the Wnt Signaling Pathway 33 Human Cancers Develop by the Stepwise Accumulation of Mutations Involving Oncogenes and Tumor Suppressor Genes 34 Genetic Instability Facilitates the Accumulation of Mutations in Cancer Cells 35 Summing Up: The Hallmarks of Cancer 37 Diagnosis, Screening, and Treatment 39 Cancer Is Diagnosed by Microscopic Examination of Tissue Specimens 39 Screening Techniques for Early Detection Can Prevent Many Cancer Deaths 40 Surgery, Radiation, and Chemotherapy Are Standard Treatments for Cancer 42 Immunotherapies Exploit the Ability of the Immune System to Recognize Cancer Cells 43 Herceptin and Gleevec Are Cancer Drugs That Act Through Molecular Targeting 44 Anti-angiogenic Therapies Act by Attacking a Tumor's Blood Supply 45 Perspective 000 Problem Set 000 Suggested Reading 000 BOX 24A Human Applications CHILDREN OF THE MOON 52 BOX 24B Experimental Techniques MONOCLONAL ANTIBODIES AND CANCER TREATMENT 54 Appendix Principles and Techniques of Microscopy A-1 Optical Principles of Microscopy A-1 The Illuminating Wavelength Sets a Limit on How Small an Object Can Be Seen A-1 Resolution Refers to the Ability to Distinguish Adjacent Objects as Separate from One Another A-0 The Practical Limit of Resolution Is Roughly 200 nm for Light Microscopy and 2 nm for Electron Microscopy A-0 The Light Microscope A-0 Compound Microscopes Use Several Lenses in Combination A-0 Phase-Contrast Microscopy Detects Differences in Refractive Index and Thickness A-0 Differential Interference Contrast (DIC) Microscopy Utilizes a Split Light Beam to Detect Phase Differences A-0 Fluorescence Microscopy Can Deteect the Presence of Specific Molecules or Ions Within Cells A-0 Confocal Microscopy Minimizes Blurring by Excluding Out-of-Focus Light from an Image A-0 Digital Video Microscopy Can Record Enhanced Time-Lapse Images A-0 Optical Methods Can Be Used to Measure the Movements and Properties of Proteins and Other Macromolecules A-0 Sample Preparation Techniques for Light Microscopy A-0 Specimen Preparation Often Involves Fixation, Sectioning, and Staining A-0 The Electron Microscope A-0 Transmission Electron Microscopy Forms an Image from Electrons that Pass Through the Specimen A-0 Scanning Electron Microscopy Reveals the Surface Architecture of Cells and Organelles A-0 Sample Preparation Techniques for Electron Microscopy A-0 Ultrathin Sectioning and Staining Are Common Preparation Techniques for Transmission Electron Microscopy A-0 Radioisotopes and Antibodies Can Localize Molecules in Electron Micrographs A-0 Correlative Microscopy Can Be Used to Bridge the Gap Between Light and Electron Microscopy A-0 Negative Staining Can Highlight Small Objects in Relief Against a Stained Background A-0 Shadowing Techniques Use Metal Vapor Sprayed Across a Specimen's Surface A-0 Freeze Fracturing and Freeze Etching Are Useful for Examining the Interior of Membranes A-0 Stereo Electron Microscopy Allows Specimens to Be Viewed in Three Dimensions A-0 Specimen Preparation for Scanning Electron Microscopy Involves Fixatin but Not Sectioning A-0 Other Imaging Methods A-0 Scanning Probe Microscopy Reveals the Surface Features of Individual Molecules A-0 X-Ray Diffraction Allows the Three-Dimensional Structure of Macromolecules to Be Determined A-0 CryoEM Bridges the Gap Between X-Ray Crystallography and Electron Microscopy A-0 Suggested Reading A-0 Glossary G-I Photo, Illustration, and Text Credits C-1 Index I-1
Library of Congress Subject Headings for this publication:
Cytology.
Molecular biology.