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Becker's World of the Cell, Global Edition

Becker's World of the Cell, Global Edition

Jeff Hardin | Gregory Paul Bertoni | Lewis J. Kleinsmith

(2017)

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Book Details

Abstract

For courses in cell biology.

 

Explore the world of the cell

 

Widely praised for its strong biochemistry coverage and clear, easy-to-follow explanations and figures, Becker’s World of the Cell provides a beautifully-illustrated, up-to-date introduction to cell biology concepts, processes, and applications. Informed by many years of classroom experience in the sophomore-level cell biology course, the dramatically-revised Ninth Edition introduces molecular genetics concepts earlier in the text and includes more extensive coverage of key techniques in each chapter. Becker’s World of the Cell provides accessible and authoritative descriptions of all major principles, as well as unique scientific insights into visualization and applications of cell and molecular biology.

 

MasteringBiologynot included. Students, if MasteringBiology is a recommended/mandatory component of the course, please ask your instructor for the correct ISBN and course ID. MasteringBiology should only be purchased when required by an instructor. Instructors, contact your Pearson representative for more information.

 

MasteringBiology is an online homework, tutorial, and assessment program designed to work with this text to engage students and improve results. Interactive, self-paced tutorials provide individualized coaching to help students stay on track. With a wide range of activities available, students can actively learn, understand, and retain even the most difficult concepts.


Table of Contents

Section Title Page Action Price
Front Cover Front Cover
About the Authors 3
Brief Contents 4
Detailed Contents 5
Preface 18
Acknowledgments 24
Chapter 1: A Preview of Cell Biology 25
1.1: The Cell Theory: A Brief History 26
Advances in Microscopy Allowed Detailed Studies of Cells 26
The Cell Theory Applies to All Organisms 26
1.2: The Emergence of Modern Cell Biology 27
The Cytological Strand Deals with Cellular Structure 29
The Biochemical Strand Studies the Chemistry of Biological Structure and Function 33
The Genetic Strand Focuses on Information Flow 35
1.3: How Do We Know What We Know? 38
Biological “Facts” May Turn Out to Be Incorrect 38
Experiments Test Specific Hypotheses 38
Model Organisms Play a Key Role in Modern Cell Biology Research 39
Well-Designed Experiments Alter Only One Variable at a Time 41
Summary of Key Points 42
Problem Set 43
Key Technique: Using Immunofluorescence to Identify Specific Cell Components 32
Human Connections: The Immortal Cells of Henrietta Lacks 40
Chapter 2: The Chemistry of the Cell 45
2.1: The Importance of Carbon 46
Carbon-Containing Molecules Are Stable 47
Carbon-Containing Molecules Are Diverse 48
Carbon-Containing Molecules Can Form Stereoisomers 49
2.2: The Importance of Water 50
Water Molecules Are Polar 51
Water Molecules Are Cohesive 52
Water Has a High Temperature-Stabilizing Capacity 52
Water Is an Excellent Solvent 52
2.3: The Importance of Selectively Permeable Membranes 55
A Membrane Is a Lipid Bilayer with Proteins Embedded in It 55
Lipid Bilayers Are Selectively Permeable 56
2.4: The Importance of Synthesis by Polymerization 56
Macromolecules Are Critical for Cellular Form and Function 56
Cells Contain Three Different Kinds of Macromolecular Polymers 58
Macromolecules Are Synthesized by Stepwise Polymerization of Monomers 59
2.5: The Importance of Self-Assembly 60
Noncovalent Bonds and Interactions Are Important in the Folding of Macromolecules 61
Many Proteins Spontaneously Fold into Their Biologically Functional State 61
Molecular Chaperones Assist the Assembly of Some Proteins 62
Self-Assembly Also Occurs in Other Cellular Structures 62
The Tobacco Mosaic Virus Is a Case Study in Self-Assembly 62
Self-Assembly Has Limits 63
Hierarchical Assembly Provides Advantages for the Cell 63
Summary of Key Points 64
Problem Set 65
Key Technique: Determining the Chemical Fingerprint of a Cell Using Mass Spectrometry 50
Human Connections: Taking a Deeper Look: Magnetic Resonance Imaging (MRI) 54
Chapter 3: The Macromolecules of the Cell 66
3.1: Proteins 67
The Monomers Are Amino Acids 67
The Polymers Are Polypeptides and Proteins 69
Several Kinds of Bonds and Interactions Are Important in Protein Folding and Stability 70
Protein Structure Depends on Amino Acid Sequence and Interactions 73
3.2: Nucleic Acids 82
The Monomers Are Nucleotides 82
The Polymers Are DNA and RNA 83
A DNA Molecule Is a Double-Stranded Helix 85
3.3: Polysaccharides 86
The Monomers Are Monosaccharides 86
The Polymers Are Storage and Structural Polysaccharides 88
Polysaccharide Structure Depends on the Kinds of Glycosidic Bonds Involved 90
3.4: Lipids 90
Fatty Acids Are the Building Blocks of Several Classes of Lipids 91
Triacylglycerols Are Storage Lipids 93
Phospholipids Are Important in Membrane Structure 93
Glycolipids Are Specialized Membrane Components 94
Steroids Are Lipids with a Variety of Functions 94
Terpenes Are Formed from Isoprene 95
Summary of Key Points 95
Problem Set 96
Human Connections: Aggregated Proteins and Alzheimer’s 71
Key Technique: Using X-Ray Crystallography to Determine Protein Structure 80
Chapter 4: Cells and Organelles 99
4.1: Where Did the First Cells Come From? 99
Simple Organic Molecules May Have Formed Abiotically in the Young Earth 99
RNA May Have Been the First Informational Molecule 100
Liposomes May Have Defined the First Primitive Protocells 101
4.2: Properties and Strategies of Cells 101
All Organisms Are Bacteria, Archaea, or Eukaryotes 101
There Are Several Limitations on Cell Size 102
Bacteria, Archaea, and Eukaryotes Differ from Each Other in Many Ways 104
4.3: The Eukaryotic Cell in Overview: Structure and Function 107
The Plasma Membrane Defines Cell Boundaries and Retains Contents 107
The Nucleus Is the Information Center of the Eukaryotic Cell 108
Mitochondria and Chloroplasts Provide Energy for the Cell 109
The Endosymbiont Theory Proposes That Mitochondria and Chloroplasts Were Derived From Bacteria 111
The Endomembrane System Synthesizes Proteins for a Variety of Cellular Destinations 113
Other Organelles Also Have Specific Functions 116
Ribosomes Synthesize Proteins in the Cytoplasm 119
The Cytoskeleton Provides Structure to the Cytoplasm 119
The Extracellular Matrix and Cell Walls Are Outside the Plasma Membrane 122
4.4: Viruses, Viroids, and Prions: Agents That Invade Cells 123
A Virus Consists of a DNA or RNA Core Surrounded by a Protein Coat 123
Viroids Are Small, Circular RNA Molecules That Can Cause Plant Diseases 124
Prions Are Infectious Protein Molecules 125
Summary of Key Points 125
Problem Set 126
Human Connections: When Cellular “Breakdown” Breaks Down 116
Key Technique: Using Centrifugation to Isolate Organelles 120
Chapter 5: Bioenergetics: The Flow of Energy in the Cell 128
5.1: The Importance of Energy 129
Cells Need Energy to Perform Six Different Kinds of Work 129
Organisms Obtain Energy Either from Sunlight or from the Oxidation of Chemical Compounds 130
Energy Flows Through the Biosphere Continuously 131
The Flow of Energy Through the Biosphere Is Accompanied by a Flow of Matter 133
5.2: Bioenergetics 133
Understanding Energy Flow Requires Knowledge of Systems, Heat, and Work 133
The First Law of Thermodynamics States That Energy Is Conserved 134
The Second Law of Thermodynamics States That Reactions Have Directionality 136
Entropy and Free Energy Are Two Means of Assessing Thermodynamic Spontaneity 137
5.3: Understanding ∆G and Keq 140
The Equilibrium Constant Keq Is a Measure of Directionality 140
∆G Can Be Calculated Readily 141
The Standard Free Energy Change Is ∆G Measured Under Standard Conditions 141
Summing Up: The Meaning of ∆G´ and ∆G˚´ 144
Free Energy Change: Sample Calculations 145
Jumping Beans Provide a Useful Analogy for Bioenergetics 146
Life Requires Steady-State Reactions That Move Toward Equilibrium Without Ever Getting There 147
Summary of Key Points 148
Problem Set 149
Human Connections: The “Potential” of Food to Provide Energy 135
Key Technique: Measuring How Molecules Bind to One Another Using Isothermal Titration Calorimetry 142
Chapter 6: Enzymes: The Catalysts of Life 151
6.1: Activation Energy and the Metastable State 152
Before a Chemical Reaction Can Occur, the Activation Energy Barrier Must Be Overcome 152
The Metastable State Is a Result of the Activation Barrier 153
Catalysts Overcome the Activation Energy Barrier 153
6.2: Enzymes as Biological Catalysts 154
Most Enzymes Are Proteins 154
Substrate Binding, Activation, and Catalysis Occur at the Active Site 157
Ribozymes Are Catalytic RNA Molecules 159
6.3: Enzyme Kinetics 161
Monkeys and Peanuts Provide a Useful Analogy for Understanding Enzyme Kinetics 161
Most Enzymes Display Michaelis–Menten Kinetics 162
What Is the Meaning of Vmax and Km? 163
Why Are Km and Vmax Important to Cell Biologists? 164
The Double-Reciprocal Plot Is a Useful Means of Visualizing Kinetic Data 164
Enzyme Inhibitors Act Either Irreversibly or Reversibly 165
6.4: Enzyme Regulation 168
Allosteric Enzymes Are Regulated by Molecules Other than Reactants and Products 168
Allosteric Enzymes Exhibit Cooperative Interactions Between Subunits 170
Enzymes Can Also Be Regulated by the Addition or Removal of Chemical Groups 170
Summary of Key Points 172
Problem Set 173
Human Connections: ACE Inhibitors: Enzyme Activity as the Difference Between Life and Death 160
Key Technique: Determining Km and Vmax Using Enzyme Assays 166
Chapter 7: Membranes: Their Structure, Function, and Chemistry 176
7.1: The Functions of Membranes 177
Membranes Define Boundaries and Serve as Permeability Barriers 177
Membranes Are Sites of Specific Proteins and Therefore of Specific Functions 177
Membrane Proteins Regulate the Transport of Solutes 178
Membrane Proteins Detect and Transmit Electrical and Chemical Signals 178
Membrane Proteins Mediate Cell Adhesion and Cell-to-Cell Communication 178
7.2: Models of Membrane Structure: An Experimental Perspective 179
Overton and Langmuir: Lipids Are Important Components of Membranes 179
Gorter and Grendel: The Basis of Membrane Structure Is a Lipid Bilayer 179
Davson and Danielli: Membranes Also Contain Proteins 180
Robertson: All Membranes Share a Common Underlying Structure 180
Further Research Revealed Major Shortcomings of the Davson–Danielli Model 180
Singer and Nicolson: A Membrane Consists of a Mosaic of Proteins in a Fluid Lipid Bilayer 181
Unwin and Henderson: Most Membrane Proteins Contain Transmembrane Segments 181
Recent Findings Suggest Membranes Are Organized into Microdomains 182
7.3: Membrane Lipids: The “Fluid” Part of the Model 183
Membranes Contain Several Major Classes of Lipids 183
Fatty Acids Are Essential to Membrane Structure and Function 185
Thin-Layer Chromatography Is an Important Technique for Lipid Analysis 185
Membrane Asymmetry: Most Lipids Are Distributed Unequally Between the Two Monolayers 186
The Lipid Bilayer Is Fluid 187
Membranes Function Properly Only in the Fluid State 187
Most Organisms Can Regulate Membrane Fluidity 190
Lipid Rafts Are Localized Regions of Membrane Lipids That Are Involved in Cell Signaling 191
7.4: Membrane Proteins: The “Mosaic” Part of the Model 192
The Membrane Consists of a Mosaic of Proteins: Evidence from Freeze-Fracture Microscopy 192
Membranes Contain Integral, Peripheral, and Lipid-Anchored Proteins 192
Membrane Proteins Can Be Isolated and Analyzed 195
Determining the Three-Dimensional Structure of Membrane Proteins Is Becoming Easier 198
Molecular Biology Has Contributed Greatly to Our Understanding of Membrane Proteins 199
Membrane Proteins Have a Variety of Functions 199
Membrane Proteins Are Oriented Asymmetrically Across the Lipid Bilayer 200
Many Membrane Proteins and Lipids Are Glycosylated 200
Membrane Proteins Vary in Their Mobility 202
The Erythrocyte Membrane Contains an Interconnected Network of Membrane-Associated Proteins 204
Summary of Key Points 205
Problem Set 206
Key Technique: SDS–Polyacrylamide Gel Electrophoresis (SDS-PAGE) of Membrane Proteins 196
Chapter 8: Transport Across Membranes: Overcoming the Permeability Barrier 209
8.1: Cells and Transport Processes 210
Solutes Cross Membranes by Simple Diffusion, Facilitated Diffusion, and Active Transport 210
The Movement of a Solute Across a Membrane Is Determined by Its Concentration Gradient or Its Electrochemical Potential 210
The Erythrocyte Plasma Membrane Provides Examples of Transport Mechanisms 212
8.2: Simple Diffusion: Unassisted Movement Down the Gradient 212
Diffusion Always Moves Solutes Toward Equilibrium 213
Osmosis Is the Diffusion of Water Across a Selectively Permeable Membrane 213
Simple Diffusion Is Typically Limited to Small, Nonpolar Molecules 215
The Rate of Simple Diffusion Is Directly Proportional to the Concentration Gradient 216
8.3: Facilitated Diffusion: Protein-Mediated Movement Down the Gradient 216
Carrier Proteins and Channel Proteins Facilitate Diffusion by Different Mechanisms 217
Carrier Proteins Alternate Between Two Conformational States 217
Carrier Proteins Are Analogous to Enzymes in Their Specificity and Kinetics 217
Carrier Proteins Transport Either One or Two Solutes 218
The Erythrocyte Glucose Transporter and Anion Exchange Protein Are Examples of Carrier Proteins 218
Channel Proteins Facilitate Diffusion by Forming Hydrophilic Transmembrane Channels 221
8.4: Active Transport: Protein-Mediated Movement Up the Gradient 225
The Coupling of Active Transport to an Energy Source May Be Direct or Indirect 225
Direct Active Transport Depends on Four Types of Transport ATPases 226
Indirect Active Transport Is Driven by Ion Gradients 228
8.5: Examples of Active Transport 229
Direct Active Transport: The Na+/K+ Pump Maintains Electrochemical Ion Gradients 229
Indirect Active Transport: Sodium Symport Drives the Uptake of Glucose 230
The Bacteriorhodopsin Proton Pump Uses Light Energy to Transport Protons 232
8.6: The Energetics of Transport 233
For Uncharged Solutes, the ∆G of Transport Depends Only on the Concentration Gradient 233
For Charged Solutes, the ∆G of TransportDepends on the Electrochemical Potential 234
Summary of Key Points 235
Problem Set 236
Key Technique: Expression of Heterologous Membrane Proteins in Frog Oocytes 220
Human Connections: Membrane Transport, Cystic Fibrosis, and the Prospects for Gene Therapy 222
Chapter 9: Chemotrophic Energy Metabolism: Glycolysis and Fermentation 239
9.1: Metabolic Pathways 240
9.2: ATP: The Primary Energy Molecule in Cells 240
ATP Contains Two Energy-Rich Phosphoanhydride Bonds 240
ATP Hydrolysis Is Highly Exergonic Due to Several Factors 241
ATP Is Extremely Important in Cellular Energy Metabolism 242
9.3: Chemotrophic Energy Metabolism 244
Biological Oxidations Usually Involve the Removal of Both Electrons and Protons and Are Highly Exergonic 244
Coenzymes Such as NAD+ Serve as Electron Acceptors in Biological Oxidations 245
Most Chemotrophs Meet Their Energy Needs by Oxidizing Organic Food Molecules 245
Glucose Is One of the Most Important Oxidizable Substrates in Energy Metabolism 246
The Oxidation of Glucose Is Highly Exergonic 246
Glucose Catabolism Yields Much More Energy in the Presence of Oxygen Than in Its Absence 246
Based on Their Need for Oxygen, Organisms Are Aerobic, Anaerobic, or Facultative 246
9.4: Glycolysis: ATP Generation Without the Involvement of Oxygen 247
Glycolysis Generates ATP by Catabolizing Glucose to Pyruvate 247
9.5: Fermentation 250
In the Absence of Oxygen, Pyruvate Undergoes Fermentation to Regenerate NAD 250
Fermentation Taps Only a Fraction of the Substrate’s Free Energy but Conserves That Energy Efficiently as ATP 252
Cancer Cells Ferment Glucose to Lactate Even in the Presence of Oxygen 252
9.6: Alternative Substrates for Glycolysis 253
Other Sugars and Glycerol Are Also Catabolized by the Glycolytic Pathway 253
Polysaccharides Are Cleaved to Form Sugar Phosphates That Also Enter the Glycolytic Pathway 254
9.7: Gluconeogenesis 255
9.8: The Regulation of Glycolysis and Gluconeogenesis 259
Key Enzymes in the Glycolytic and Gluconeogenic Pathways Are Subject to Allosteric Regulation 259
Fructose-2,6-Bisphosphate Is an Important Regulator of Glycolysis and Gluconeogenesis 260
9.9: Novel Roles for Glycolytic Enzymes 261
Summary of Key Points 262
Problem Set 263
Key Technique: Using Isotopic Labeling to Determine the Fate of Atoms in a Metabolic Pathway 256
Human Connections: What Happens to the Sugar? 258
Chapter 10: Chemotrophic Energy Metabolism: Aerobic Respiration 266
10.1: Cellular Respiration: Maximizing ATP Yields 267
Aerobic Respiration Yields Much More Energy than Fermentation Does 267
Respiration Includes Glycolysis, Pyruvate Oxidation, the Citric Acid Cycle, Electron Transport, and ATP Synthesis 267
10.2: The Mitochondrion: Where the Action Takes Place 267
Mitochondria Are Often Present Where the ATP Needs Are Greatest 269
Are Mitochondria Interconnected Networks Rather than Discrete Organelles? 269
The Outer and Inner Membranes Define Two Separate Compartments and Three Regions 270
Mitochondrial Functions Occur in or on Specific Membranes and Compartments 271
In Bacteria, Respiratory Functions Are Localized to the Plasma Membrane and the Cytoplasm 273
10.3: The Citric Acid Cycle: Oxidation in the Round 274
Pyruvate Is Converted to Acetyl Coenzyme A by Oxidative Decarboxylation 275
The Citric Acid Cycle Begins with the Entry of Acetate as Acetyl CoA 275
Two Oxidative Decarboxylations Then Form NADH and Release CO2 276
Direct Generation of GTP (or ATP) Occurs at One Step in the Citric Acid Cycle 276
The Final Oxidative Reactions of the Citric Acid Cycle Generate FADH2 and NADH 276
Summing Up: The Products of the Citric Acid Cycle Are CO2, ATP, NADH, and FADH2 278
Several Citric Acid Cycle Enzymes Are Subject to Allosteric Regulation 279
The Citric Acid Cycle Also Plays a Central Role in the Catabolism of Fats and Proteins 279
The Citric Acid Cycle Serves as a Source of Precursors for Anabolic Pathways 282
The Glyoxylate Cycle Converts Acetyl CoA to Carbohydrates 282
10.4: Electron Transport: Electron Flow from Coenzymes to Oxygen 284
The Electron Transport System Conveys Electrons from Reduced Coenzymes to Oxygen 284
The Electron Transport System Consists of Five Kinds of Carriers 285
The Electron Carriers Function in a Sequence Determined by Their Reduction Potentials 286
Most of the Carriers Are Organized into Four Large Respiratory Complexes 288
The Respiratory Complexes Move Freely Within the Inner Membrane 290
10.5: The Electrochemical Proton Gradient: Key to Energy Coupling 292
Electron Transport and ATP Synthesis Are Coupled Events 292
Coenzyme Oxidation Pumps Enough Protons to Form Three ATP Molecules per NADH and Two ATP Molecules per FADH2 293
The Chemiosmotic Model Is Affirmed by an Impressive Array of Evidence 293
10.6: ATP Synthesis: Putting It All Together 295
F1 Particles Have ATP Synthase Activity 295
Proton Translocation Through Fo Drives ATP Synthesis by F1 297
ATP Synthesis by FoF1 Involves Physical Rotation of the Gamma Subunit 298
The Chemiosmotic Model Involves Dynamic Transmembrane Proton Traffic 300
10.7: Aerobic Respiration: Summing It All Up 301
The Maximum ATP Yield of Aerobic Respiration Is 38 ATP Molecules per Glucose 302
Aerobic Respiration Is a Highly Efficient Process 303
Summary of Key Points 303
Problem Set 304
Key Technique: Visualizing Cellular Structures with Three-Dimensional Electron Microscopy 272
Human Connections A Diet Worth Dying For? 296
Chapter 11: Phototrophic Energy Metabolism: Photosynthesis 307
11.1: An Overview of Photosynthesis 308
The Energy Transduction Reactions Convert Solar Energy to Chemical Energy 308
The Carbon Assimilation Reactions Fix Carbon by Reducing Carbon Dioxide 308
The Chloroplast Is the Photosynthetic Organelle in Eukaryotic Cells 310
Chloroplasts Are Composed of Three Membrane Systems 310
11.2: Photosynthetic Energy Transduction I: Light Harvesting 313
Chlorophyll Is Life’s Primary Link to Sunlight 313
Accessory Pigments Further Expand Access to Solar Energy 314
Light-Gathering Molecules Are Organized into Photosystems and Light-Harvesting Complexes 315
Oxygenic Phototrophs Have Two Types of Photosystems 316
11.3: Photosynthetic Energy Transduction II: NADPH Synthesis 316
Photosystem II Transfers Electrons from Water to a Plastoquinone 316
The Cytochrome b6/f Complex Transfers Electrons from a Plastoquinol to Plastocyanin 319
Photosystem I Transfers Electrons from Plastocyanin to Ferredoxin 319
Ferredoxin-NADP+ Reductase Catalyzes the Reduction of NADP 319
11.4: Photosynthetic Energy Transduction III: ATP Synthesis 322
The ATP Synthase Complex Couples Transport of Protons Across the Thylakoid Membrane to ATP Synthesis 322
Cyclic Photophosphorylation Allows a Photosynthetic Cell to Balance NADPH and ATP Synthesis 322
A Summary of the Complete Energy Transduction System 323
Bacteria Use a Photosynthetic Reaction Center and Electron Transport System Similar to Those in Plants 323
11.5: Photosynthetic Carbon Assimilation I: The Calvin Cycle 324
Carbon Dioxide Enters the Calvin Cycle by Carboxylation of Ribulose-1,5-Bisphosphate 325
3-Phosphoglycerate Is Reduced to Form Glyceraldehyde-3-Phosphate 325
Regeneration of Ribulose-1,5-Bisphosphate Allows Continuous Carbon Assimilation 327
The Complete Calvin Cycle and Its Relation to Photosynthetic Energy Transduction 327
11.6: Regulation of the Calvin Cycle 328
The Calvin Cycle Is Highly Regulated to Ensure Maximum Efficiency 328
Rubisco Activase Regulates Carbon Fixation by Rubisco 328
11.7: Photosynthetic Carbon Assimilation II: Carbohydrate Synthesis 329
Glucose-1-Phosphate Is Synthesized from Triose Phosphates 329
The Biosynthesis of Sucrose Occurs in the Cytosol 330
The Biosynthesis of Starch Occurs in the Chloroplast Stroma 330
Photosynthesis Also Produces Reduced Nitrogen and Sulfur Compounds 330
11.8: Rubisco’s Oxygenase Activity Decreases Photosynthetic Efficiency 331
The Glycolate Pathway Returns Reduced Carbon from Phosphoglycolate to the Calvin Cycle 331
C4 Plants Minimize Photorespiration by Confining Rubisco to Cells Containing High Concentrations of CO2 333
CAM Plants Minimize Photorespiration and Water Loss by Opening Their Stomata Only at Night 335
Summary of Key Points 336
Problem Set 337
Key Technique: Determining Absorption and Action Spectra via Spectrophotometry 312
Human Connections: How do Plants Put on Sunscreen? 320
Chapter 12: The Endomembrane System 338
12.1: The Endoplasmic Reticulum 339
The Two Basic Kinds of Endoplasmic Reticulum Differ in Structure and Function 340
Rough ER Is Involved in the Biosynthesis and Processing of Proteins 340
Smooth ER Is Involved in Drug Detoxification, Carbohydrate Metabolism, Calcium Storage, and Steroid Biosynthesis 341
The ER Plays a Central Role in the Biosynthesis of Membranes 343
12.2: The Golgi Apparatus 343
The Golgi Apparatus Consists of a Series of Membrane-Bounded Cisternae 343
Two Models Account for the Flow of Lipids and Proteins Through the Golgi Apparatus 344
12.3: Roles of the ER and Golgi Apparatus in Protein Glycosylation 345
Initial Glycosylation Occurs in the ER 345
Further Glycosylation Occurs in the Golgi Apparatus 346
12.4: Roles of the ER and Golgi Apparatus in Protein Trafficking 348
ER-Specific Proteins Contain Retention and Retrieval Tags 348
Golgi Apparatus Proteins May Be Sorted According to the Lengths of Their Membrane-Spanning Domains 349
Targeting of Soluble Lysosomal Proteins to Endosomes and Lysosomes Is a Model for Protein Sorting in the TGN 349
12.5: Exocytosis and Endocytosis: Transporting Material Across the Plasma Membrane 351
Secretory Pathways Transport Molecules to the Exterior of the Cell 351
Exocytosis Releases Intracellular Molecules Outside the Cell 352
Endocytosis Imports Extracellular Molecules by Forming Vesicles from the Plasma Membrane 353
12.6: Coated Vesicles in Cellular Transport Processes 360
Clathrin-Coated Vesicles Are Surrounded by Lattices Composed of Clathrin and Adaptor Protein 360
The Assembly of Clathrin Coats Drives the Formation of Vesicles from the Plasma Membrane and TGN 361
COPI- and COPII-Coated Vesicles Travel Between the ER and Golgi Apparatus Cisternae 362
SNARE Proteins Mediate Fusion Between Vesicles and Target Membranes 362
12.7: Lysosomes and Cellular Digestion 364
Lysosomes Isolate Digestive Enzymes from the Rest of the Cell 364
Lysosomes Develop from Endosomes 364
Lysosomal Enzymes Are Important for Several Different Digestive Processes 365
Lysosomal Storage Diseases Are Usually Characterized by the Accumulation of Indigestible Material 367
12.8: The Plant Vacuole: A Multifunctional Organelle 368
12.9: Peroxisomes 368
Most Peroxisomal Functions Are Linked to Hydrogen Peroxide Metabolism 369
Plant Cells Contain Types of Peroxisomes Not Found in Animal Cells 370
Peroxisome Biogenesis Can Occur by Division of Preexisting Peroxisomes or by Vesicle Fusion 370
Summary of Key Points 371
Problem Set 372
Key Technique: Visualizing Vesicles at the Cell Surface Using Total Internal Reflection (TIRF) Microscopy 354
Human Connections: It’s All in the Family 357
Chapter 13: Cytoskeletal Systems 375
13.1: Major Structural Elements of the Cytoskeleton 376
Eukaryotes Have Three Basic Types of Cytoskeletal Elements 376
Bacteria Have Cytoskeletal Systems That Are Structurally Similar to Those in Eukaryotes 376
The Cytoskeleton Is Dynamically Assembled and Disassembled 376
13.2: Microtubules 378
Two Types of Microtubules Are Responsible for Many Functions in the Cell 378
Tubulin Heterodimers Are the Protein Building Blocks of Microtubules 378
Microtubules Can Form as Singlets, Doublets, or Triplets 379
Microtubules Form by the Addition of Tubulin Dimers at Their Ends 379
Addition of Tubulin Dimers Occurs More Quickly at the Plus Ends of Microtubules 381
Drugs Can Affect the Assembly and Stability of Microtubules 381
GTP Hydrolysis Contributes to the Dynamic Instability of Microtubules 382
Microtubules Originate from Microtubule-Organizing Centers Within the Cell 383
MTOCs Organize and Polarize Microtubules Within Cells 384
Microtubule Stability Is Tightly Regulated in Cells by a Variety of Microtubule-Binding Proteins 386
13.3: Microfilaments 388
Actin Is the Protein Building Block of Microfilaments 389
Different Types of Actin Are Found in Cells 389
G-Actin Monomers Polymerize into F-Actin Microfilaments 389
Specific Drugs Affect Polymerization of Microfilaments 390
Cells Can Dynamically Assemble Actin into a Variety of Structures 390
Actin-Binding Proteins Regulate the Polymerization, Length, and Organization of Microfilaments 390
Proteins That Link Actin to Membranes 393
Phospholipids and Rho Family GTPases Regulate Where and When Actin-Based Structures Assemble 394
13.4: Intermediate Filaments 396
Intermediate Filament Proteins Are Tissue Specific 397
Intermediate Filaments Assemble from Fibrous Subunits 398
Intermediate Filaments Confer Mechanical Strength on Tissues 398
The Cytoskeleton Is a Mechanically Integrated Structure 399
Summary of Key Points 399
Problem Set 400
Key Technique: Studying the Dynamic Cytoskeleton 386
Human Connections: When Actin Kills 395
Chapter 14: Cellular Movement: Motility and Contractility 401
14.1: Microtubule-Based Movement Inside Cells: Kinesins and Dyneins 403
Motor Proteins Move Cargoes Along MTs During Axonal Transport 403
Classic Kinesins Move Toward the Plus Ends of Microtubules 404
Kinesins Are a Large Family of Proteins 404
Dyneins Are Found in Axonemes and the Cytosol 404
Microtubule Motors Direct Vesicle Transport and Shape the Endomembrane System 408
14.2: Microtubule-Based Cell Motility: Cilia and Flagella 408
Cilia and Flagella Are Common Motile Appendages of Eukaryotic Cells 408
Cilia and Flagella Consist of an Axoneme Connected to a Basal Body 409
Doublet Sliding Within the Axoneme Causes Cilia and Flagella to Bend 410
14.3: Microfilament-Based Movement Inside Cells: Myosins 411
Myosins Are a Large Family of Actin-Based Motors with Diverse Roles in Cell Motility 411
Many Myosins Move Along Actin Filaments in Short Steps 413
14.4: Microfilament-Based Motility: Muscle Cells in Action 413
Skeletal Muscle Cells Contain Thin and Thick Filaments 413
Sarcomeres Contain Ordered Arrays of Actin, Myosin, and Accessory Proteins 414
The Sliding-Filament Model Explains Muscle Contraction 416
Cross-Bridges Hold Filaments Together, and ATP Powers Their Movement 418
The Regulation of Muscle Contraction Depends on Calcium 418
The Coordinated Contraction of Cardiac Muscle Cells Involves Electrical Coupling 421
Smooth Muscle Is More Similar to Nonmuscle Cells than to Skeletal Muscle 422
14.5: Microfilament-Based Motility in Nonmuscle Cells 423
Cell Migration via Lamellipodia Involves Cycles of Protrusion, Attachment,Translocation, and Detachment 423
Chemotaxis Is a Directional Movement in Response to a Graded Chemical Stimulus 425
Amoeboid Movement Involves Cycles of Gelation and Solation of Actin 425
Actin-Based Motors Move Components Within the Cytosol of Some Cells 426
Summary of Key Points 426
Problem Set 427
Key Technique: Watching Motors Too Small to See 406
Human Connections: Dyneins Help Us Tell Left from Right 412
Chapter 15: Beyond the Cell: Cell Adhesions, Cell Junctions, and Extracellular Structures 429
15.1: Cell-Cell Junctions 430
Adhesive Junctions Link Adjoining Cells 430
Transient Cell-Cell Adhesions Are Importantf or Many Cellular Events 433
Tight Junctions Prevent the Movement of Molecules Across Cell Layers 434
Gap Junctions Allow Direct Electrical and Chemical Communication Between Cells 438
15.2: The Extracellular Matrix of Animal Cells 439
Collagens Are Responsible for the Strength of the Extracellular Matrix 439
Elastins Impart Elasticity and Flexibility to the Extracellular Matrix 440
Collagen and Elastin Fibers Are Embedded in a Matrix of Proteoglycans 441
Free Hyaluronate Lubricates Joints and Facilitates Cell Migration 443
Adhesive Glycoproteins Anchor Cells to the Extracellular Matrix 443
Fibronectins Bind Cells to the ECM and Guide Cellular Movement 443
Laminins Bind Cells to the Basal Lamina 444
Integrins Are Cell Surface Receptors That Bind ECM Components 444
The Dystrophin/Dystroglycan Complex Stabilizes Attachments of Muscle Cells to the ECM 448
15.3: The Plant Cell Surface 449
Cell Walls Provide a Structural Framework and Serve as a Permeability Barrier 449
The Plant Cell Wall Is a Network of Cellulose Microfibrils, Polysaccharides, and Glycoproteins 449
Cell Walls Are Synthesized in Several Discrete Stages 450
Plasmodesmata Permit Direct Cell-Cell Communication Through the Cell Wall 451
Summary of Key Points 452
Problem Set 453
Human Connections: The Costly Effects of Weak Adhesion 435
Key Technique: Building an ECM from Scratch 446
Chapter 16: The Structural Basis of Cellular Information: DNA, Chromosomes, and the Nucleus 455
16.1: Chemical Nature of the Genetic Material 456
The Discovery of DNA Led to Conflicting Proposals Concerning the Chemical Nature of Genes 456
Avery Showed That DNA Is the Genetic Material of Bacteria 457
Hershey and Chase Showed That DNA Is the Genetic Material of Viruses 457
RNA Is the Genetic Material in Some Viruses 459
16.2: DNA Structure 461
Chargaff’s Rules Reveal That A = T and G = C 461
Watson and Crick Discovered That DNA Is a Double Helix 462
DNA Can Be Interconverted Between Relaxed and Supercoiled Forms 464
The Two Strands of a DNA Double Helix Can Be Denatured and Renatured 466
16.3: DNA Packaging 467
Bacteria Package DNA in Bacterial Chromosomes and Plasmids 467
Eukaryotes Package DNA in Chromatin and Chromosomes 470
Nucleosomes Are the Basic Unit of Chromatin Structure 470
A Histone Octamer Forms the Nucleosome Core 471
Nucleosomes Are Packed Together to Form Chromatin Fibers and Chromosomes 471
Changes in Histones and Chromatin Remodeling Proteins Can Alter Chromatin Packing 473
Chromosomal DNA Contains Euchromatin and Heterochromatin 474
Some Heterochromatin Plays a Structural Role in Chromosomes 474
Chromosomes Can Be Identified by Unique Banding Patterns 474
Eukaryotic Chromosomes Contain Large Amounts of Repeated DNA Sequences 475
Eukaryotes Package Some of Their DNA in Mitochondria and Chloroplasts 477
16.4: The Nucleus 478
A Double-Membrane Nuclear Envelope Surrounds the Nucleus 478
Molecules Enter and Exit the Nucleus Through Nuclear Pores 480
The Nucleus Is Mechanically Integrated with the Rest of the Cell 483
Chromatin Is Located Within the Nucleus in a Nonrandom Fashion 484
The Nucleolus Is Involved in Ribosome Formation 484
Summary of Key Points 486
Problem Set 486
Key Technique: FISHing for Specific Sequences 468
Human Connections: Lamins and Premature Aging 485
Chapter 17: DNA Replication, Repair, and Recombination 488
17.1: DNA Replication 489
DNA Synthesis Occurs During S Phase 489
DNA Replication Is Semiconservative 489
DNA Replication Is Usually Bidirectional 491
Replication Initiates at Specialized DNA Elements 494
DNA Polymerases Catalyze the Elongation of DNA Chains 495
DNA Is Synthesized as Discontinuous Segments That Are Joined Together by DNA Ligase 498
In Bacteria, Proofreading Is Performed bythe 3‘ -> 5‘ Exonuclease Activity of DNA Polymerase 499
RNA Primers Initiate DNA Replication 500
The DNA Double Helix Must Be Locally Unwound During Replication 502
DNA Unwinding and DNA Synthesis Are Coordinated on Both Strands Via the Replisome 503
Eukaryotes Disassemble and Reassemble Nucleosomes as Replication Proceeds 503
Telomeres Solve the DNA End-Replication Problem 505
17.2: DNA Damage and Repair 508
Mutations Can Occur Spontaneously During Replication 508
Mutagens Can Induce Mutations 510
DNA Repair Systems Correct Many Kinds of DNA Damage 512
17.3: Homologous Recombination and Mobile Genetic Elements 517
Homologous Recombination Is Initiated by Double-Stranded Breaks in DNA 517
Transposons Are Mobile Genetic Elements 519
Transposons Differ Based on Their Autonomy and Mechanism of Movement 519
Bacterial Transposons Can Be Composite or Non-composite 520
Eukaryotes Also Have Transposons 521
Summary of Key Points 521
Problem Set 521
Key Technique: The Polymerase Chain Reaction (PCR) 500
Human Connections: Children of the Moon 514
Chapter 18: Gene Expression: I. The Genetic Code and Transcription 523
18.1: The Genetic Code and the Directional Flow of Genetic Information 524
Transcription and Translation Involve Many of the Same Components in Prokaryotes and Eukaryotes 524
Where Transcription and Translation Occur Differs in Prokaryotes and Eukaryotes 524
In Some Cases RNA Is Reversed Transcribed into DNA 526
The Genetic Code 527
The Genetic Code Is a Triplet Code 529
The Genetic Code Is Degenerate and Nonoverlapping 530
Messenger RNA Guides the Synthesis of Polypeptide Chains 531
The Codon Dictionary Was Established Using Synthetic RNA Polymers and Triplets 532
Of the 64 Possible Codons in Messenger RNA, 61 Encode Amino Acids 532
The Genetic Code Is (Nearly) Universal 533
18.2: Mechanisms of Transcription 534
Transcription Involves Four Stages: RNA Polymerase Binding, Initiation, Elongation, and Termination 534
Bacterial Transcription Involves σ Factor Binding, Initiation, Elongation, andTermination 534
Transcription in Eukaryotic Cells Has Additional Complexity Compared with Prokaryotes 540
RNA Polymerases I, II, and III Carry Out Transcription in the Eukaryotic Nucleus 540
Three Classes of Promoters Are Found in Eukaryotic Nuclear Genes, One for Each Type of RNA Polymerase 541
General Transcription Factors Are Involved in the Transcription of All Nuclear Genes 543
Elongation, Termination, and RNA Cleavage Are Involved in Completing Eukaryotic RNA Synthesis 544
18.3: RNA Processing and Turnover 545
The Nucleolus Is Involved in Ribosome Formation 545
Ribosomal RNA Processing Involves Cleavage of Multiple rRNAs from a Common Precursor 546
Transfer RNA Processing Involves Removal, Addition, and Chemical Modification of Nucleotides 548
Messenger RNA Processing in Eukaryotes Involves Capping, Addition of Poly(A), and Removal of Introns 549
Spliceosomes Remove Introns from Pre-mRNA 551
Some Introns Are Self-Splicing 552
The Existence of Introns Permits Alternative Splicing and Exon Shuffling 553
Cells Localize Nuclear RNAs in Several Types of Processing Centers 554
Nucleic Acid Editing Allows Sequences to Be Altered 554
The C-Terminal Domain of RNA Polymerase II Coordinates RNA Processing 555
Most mRNA Molecules Have a Relatively Short Life Span 555
The Abundance of mRNA Allows Amplification of Genetic Information 555
Summary of Key Points 556
Problem Set 556
Key Technique: Hunting for DNA-Protein Interactions 536
Chapter 19: Gene Expression: II. Protein Synthesis and Sorting 559
19.1: Translation: The Cast of Characters 560
Ribosomes Carry Out Polypeptide Synthesis 560
Transfer RNA Molecules Bring Amino Acids to the Ribosome 561
Aminoacyl-tRNA Synthetases Link Amino Acids to the Correct Transfer RNAs 564
Messenger RNA Brings Polypeptide Coding Information to the Ribosome 565
Protein Factors Are Required for Translational Initiation, Elongation, and Termination 566
19.2: The Mechanism of Translation 566
Translational Initiation Requires Initiation Factors, Ribosomal Subunits, mRNA, and Initiator tRNA 566
Chain Elongation Involves Cycles of Aminoacyl tRNA Binding, Peptide Bond Formation, and Translocation 570
Most mRNAs Are Read by Many Ribosomes Simultaneously 572
Termination of Polypeptide Synthesis Is Triggered by Release Factors That Recognize Stop Codons 572
Polypeptide Folding Is Facilitated by Molecular Chaperones 572
Protein Synthesis Typically Utilizes a Substantial Fraction of a Cell’s Energy Budget 574
A Summary of Translation 575
19.3: Mutations and Translation 575
Suppressor tRNAs Overcome the Effects of Some Mutations 576
Nonsense-Mediated Decay and Nonstop Decay Promote the Destruction of Defective mRNAs 577
19.4: Posttranslational Processing 577
19.5: Protein Targeting and Sorting 580
Cotranslational Import Allows Some Polypeptides to Enter the ER as They Are Being Synthesized 580
The Signal Recognition Particle (SRP) Attachesthe Ribosome-mRNA-Polypeptide Complex to the ER Membrane 584
Protein Folding and Quality Control Take Place Within the ER 585
Proteins Released into the ER Lumen Are Routed to the Golgi Apparatus, Secretory Vesicles, Lysosomes, or Back to the ER 585
Stop-Transfer Sequences Mediate the Insertion of Integral Membrane Proteins 586
Posttranslational Import Is an Alternative Mechanism for Import into the ER Lumen 586
Posttranslational Import Across Two Membranes Allows Some Polypeptides to Enter Mitochondria and Chloroplasts 588
Summary of Key Points 590
Problem Set 591
Key Technique: Protein Localization Using Fluorescent Fusion Proteins 578
Human Connections: To Catch a Killer: The Problem of Antibiotic Resistance in Bacteria 583
Chapter 20: The Regulation of Gene Expression 593
20.1: Bacterial Gene Regulation 594
Catabolic and Anabolic Pathways Are Regulated Through Induction and Repression, Respectively 594
The Genes Involved in Lactose Catabolism Are Organized into an Inducible Operon 595
The lac Operon Is Negatively Regulated by the lac Repressor 595
Studies of Mutant Bacteria Revealed How the lac Operon Is Organized 597
Catabolite Activator Protein (CAP) Positively Regulates the lac Operon 599
The lac Operon Is an Example of the Dual Control of Gene Expression 599
The Structure of the lac Repressor/Operator Complex Confirms the Operon Model 600
The Genes Involved in Tryptophan Synthesis Are Organized into a Repressible Operon 600
Sigma Factors Determine Which Sets of Genes Can Be Expressed 600
Attenuation Allows Transcription to Be Regulated After the Initiation Step 601
Riboswitches Allow Transcription and Translation to Be Controlled by Small-Molecule Interactions with RNA 603
The CRISPR/Cas System Protects Bacteria Against Viral Infection 604
20.2: Eukaryotic Gene Regulation: Genomic Control 605
Multicellular Eukaryotes Are Composed of Numerous Specialized Cell Types 605
Eukaryotic Gene Expression Is Regulated at Five Main Levels 605
The Cells of a Multicellular Organism Usually Contain the Same Set of Genes 606
Gene Amplification and Deletion Can Alter the Genome 608
DNA Rearrangements Can Alter the Genome 609
Chromatin Decondensation Is Involved in Genomic Control 610
DNA Methylation Is Associated with Inactive Regions of the Genome 611
20.3: Eukaryotic Gene Regulation: Transcriptional Control 615
Different Sets of Genes Are Transcribed in Different Cell Types 615
Proximal Control Elements Lie Close to the Promoter 616
Enhancers and Silencers Are DNA Elements Located at Variable Distances from the Promoter 617
Coactivators Mediate the Interaction Between Regulatory Transcription Factors and the RNA Polymerase Complex 619
Multiple DNA Control Elements and Transcription Factors Act in Combination 620
DNA-Binding and Activation Domains of Regulatory Transcription Factors Are Functionally Separable 620
Several Common Types of Transcription Factors Bind to DNA and Activate Transcription 621
DNA Response Elements Coordinate the Expression of Nonadjacent Genes 623
Steroid Hormone Receptors Act as Transcription Factors That Bind to Hormone Response Elements 623
CREBs and STATs Are Examples of Transcription Factors Activated by Phosphorylation 624
The Heat-Shock Response Element Coordinates Stress Responses 625
Homeotic Genes Encode Transcription Factors That Regulate Embryonic Development 625
20.4: Eukaryotic Gene Regulation: Posttranscriptional Control 627
Control of RNA Processing and Nuclear Export Follows Transcription 627
Translation Rates Can Be Controlled by Initiation Factors and Translational Repressors 627
Translation Can Also Be Controlled by Regulation of mRNA Degradation 629
RNA Interference Utilizes Small RNAs to Silence Gene Expression 630
MicroRNAs Produced by Normal Cellular Genes Silence the Translation of mRNAs 631
Piwi-interacting RNAs Are Small Regulatory RNAs That Protect the Germline of Eukaryotes 634
Long Noncoding RNAs Play a Variety of Roles in Eukaryotic Gene Regulation 634
Posttranslational Control Involves Modifications of Protein Structure, Function, and Degradation 634
Ubiquitin Targets Proteins for Degradation by Proteasomes 635
A Summary of Eukaryotic Gene Regulation 636
Summary of Key Points 637
Problem Set 638
Human Connections: The Epigenome: Methylation and Disease 613
Key Technique: Gene Knockdown via RNAi 632
Chapter 21: Molecular Biology Techniques for Cell Biology 640
21.1: Analyzing and Manipulating DNA 640
Gel Electrophoresis Allows DNA to Be Separated by Size 641
Restriction Endonucleases Cleave DNA Molecules at Specific Sites 642
Restriction Mapping Can Characterize DNA 643
Restriction Endonucleases Can Identify Methylated DNA 644
Southern Blotting Identifies Specific DNAs from a Mixture 644
Restriction Enzymes Allow Production of Recombinant DNA 645
PCR Is Widely Used to Clone Genes 646
Genomic and cDNA Libraries Are Both Useful for DNA Cloning 646
Rapid Procedures Exist for DNA Sequencing 651
21.2: Analyzing Genomes 654
Whole Genomes Can Be Sequenced 654
Comparative Genomics Allows Comparison of Genomes and Genes Within Them 656
The Field of Bioinformatics Helps to Decipher Genomes 657
Tiny Differences in Genome Sequence Distinguish People from One Another 660
21.3: Analyzing RNA and Proteins 663
Several Techniques Allow Detection of mRNAs in Time and Space 663
The Transcription of Thousands of Genes Can Be Assessed Simultaneously 664
Proteins Can Be Studied Using Electrophoresis 665
Antibodies Can Be Used to Study Specific Proteins 665
Proteins Can Be Isolated by Size, Charge, or Affinity 667
Proteins Can Be Identified from Complex Mixtures Using Mass Spectrometry 668
Protein Function Can Be Studied Using Molecular Biology Techniques 669
Protein-Protein Interactions Can Be Studied in a Variety of Ways 670
21.4: Analyzing and Manipulating Gene Function 672
Transgenic Organisms Carry Foreign Genes That Are Passed On to Subsequent Generations 672
Transcriptional Reporters Are Useful for Studying Regulation of Gene Expression 674
The Role of Specific Genes Can Be Assessed By Identifying Mutations and by Knockdown 674
Genetic Engineering Can Produce Valuable Proteins That Are Otherwise Difficult to Obtain 677
Food Crops Can Be Genetically Modified 678
Gene Therapies Are Being Developed for the Treatment of Human Diseases 678
Summary of Key Points 679
Problem Set 680
Key Technique: DNA Cloning 648
Human Connections: More Than Your Fingertips: Identifying Genetic “Fingerprints” 662
Chapter 22: Signal Transduction Mechanisms: I. Electrical and Synaptic Signaling in Neurons 682
22.1: Neurons and Membrane Potential 683
Neurons Are Specially Adapted for the Transmission of Electrical Signals 683
Neurons Undergo Changes in Membrane Potential 684
Resting Membrane Potential Depends on Ion Concentrations and Selective Membrane Permeability 685
The Nernst Equation Describes the Relationship Between Membrane Potential and Ion Concentration 686
Steady-State Ion Concentrations Affect Resting Membrane Potential 686
The Goldman Equation Describes the Combined Effects of Ions on Membrane Potential 687
22.2: Electrical Excitability and the Action Potential 688
Patch Clamping and Molecular Biological Techniques Allow Study of Single Ion Channels 688
Specific Domains of Voltage-Gated Channels Act as Sensors and Inactivators 688
Action Potentials Propagate Electrical Signals Along an Axon 692
Action Potentials Involve Rapid Changes in the Membrane Potential of the Axon 692
Action Potentials Result from the Rapid Movement of Ions Through Axonal Membrane Channels 692
Action Potentials Are Propagated Along the Axon Without Losing Strength 694
The Myelin Sheath Acts Like an Electrical Insulator Surrounding the Axon 695
22.3: Synaptic Transmission and Signal Integration 697
Neurotransmitters Relay Signals Across Nerve Synapses 697
Elevated Calcium Levels Stimulate Secretion of Neurotransmitters from Presynaptic Neurons 700
Secretion of Neurotransmitters Involves the Docking and Fusion of Vesicles with the Plasma Membrane 701
Neurotransmitters Are Detected by Specific Receptors on Postsynaptic Neurons 703
Neurotransmitters Must Be Inactivated Shortly After Their Release 704
Postsynaptic Potentials Integrate Signals from Multiple Neurons 704
Summary of Key Points 705
Problem Set 706
Key Technique: Patch Clamping 690
Human Connections: In the Search for the Fountain of Youth, Are People Paying for Poison? 702
Chapter 23: Signal Transduction Mechanisms: II. Messengers and Receptors 708
23.1: Chemical Signals and Cellular Receptors 709
Chemical Signaling Involves Several Key Components 709
Receptor Binding Involves Quantitative Interactions Between Ligands and Their Receptors 710
Cells Can Amplify Signals Once They Are Received 711
Cell-Cell Signals Act Through a Limited Number of Receptors and Signal Transduction Pathways 711
23.2: G Protein–Coupled Receptors 713
G Protein–Coupled Receptors Act Via Hydrolysis of GTP 713
Cyclic AMP Is a Second Messenger Whose Production Is Regulated by Some G Proteins 715
Disruption of G Protein Signaling Causes Human Disease 716
Many G Proteins Act Through Inositol Trisphosphate and Diacylglycerol 717
The Release of Calcium Ions Is a Key Event in Many Signaling Processes 718
23.3: Protein Kinase-Associated Receptors 722
Growth Factors Often Bind Protein Kinase-Associated Receptors 723
Receptor Tyrosine Kinases Aggregate and Undergo Autophosphorylation 723
Receptor Tyrosine Kinases Initiate a Signal Transduction Cascade Involving Ras and MAP Kinase 724
The Key Steps in RTK Signaling Can Be Dissected Using Mutants 725
Receptor Tyrosine Kinases Activate a Variety of Other Signaling Pathways 727
Other Growth Factors Transduce Their Signals via Receptor Serine-Threonine Kinases 727
23.4: Putting It All Together: Signal Integration 728
Scaffolding Complexes Can Facilitate Cell Signaling 729
Different Signaling Pathways Are Integrated Through Crosstalk 730
23.5: Hormones and Other Long-Range Signals 731
Hormones Can Be Classified by Their Chemical Properties 731
The Endocrine System Controls Multiple Signaling Pathways to Regulate Glucose Levels 731
Steroid Hormones Bind Hormones in the Cytosol and Carry Them into the Nucleus 733
Gases Can Act as Cell Signals 734
Summary of Key Points 736
Problem Set 737
Key Technique: Calcium Indicators and Ionophore 721
Human Connections: The Gas That Prevents a Heart Attack 735
Chapter 24: The Cell Cycle and Mitosis 738
24.1: Overview of the Cell Cycle 739
24.2: Nuclear and Cell Division 743
Mitosis Is Subdivided into Prophase, Prometaphase, Metaphase, Anaphase, and Telophase 743
The Mitotic Spindle Is Responsible for Chromosome Movements During Mitosis 746
Cytokinesis Divides the Cytoplasm 749
Bacteria and Eukaryotic Organelles Divide in a Different Manner from Eukaryotic Cells 752
24.3: Regulation of the Cell Cycle 753
Cell Cycle Length Varies Among Different Cell Types 753
Cell Cycle Progression Is Controlled at Several Key Transition Points 754
Cell Fusion Experiments and Cell Cycle Mutants Identified Molecules That Control the Cell Cycle 755
Progression Through the Cell Cycle Is Controlled by Cyclin-Dependent Kinases (Cdks) 755
Cdk-Cyclin Complexes Are Regulated 756
The Anaphase-Promoting Complex Allows Exit from Mitosis 758
Checkpoint Pathways Monitor Key Steps in the Cell Cycle 758
Putting It All Together: The Cell Cycle Regulation Machine 761
24.4: Growth Factors and Cell Proliferation 762
Stimulatory Growth Factors Activate the Ras Pathway 762
Stimulatory Growth Factors Can Also Activate the PI 3-Kinase–Akt Pathway 763
Inhibitory Growth Factors Act Through Cdk Inhibitors 764
24.5: Apoptosis 764
Apoptosis Is Triggered by Death Signals or Withdrawal of Survival Factors 765
Summary of Key Points 767
Problem Set 768
Key Technique: Measuring Cells Millions at a Time 740
Human Connections: What Do Ethnobotany and Cancer Have in Common? 750
Chapter 25: Sexual Reproduction, Meiosis, and Genetic Recombination 770
25.1: Sexual Reproduction 771
Sexual Reproduction Produces Genetic Variety 771
Gametes Are Haploid Cells Specialized for Sexual Reproduction 771
25.2: Meiosis 771
The Life Cycles of Sexual Organisms Have Diploid and Haploid Phases 772
Meiosis Converts One Diploid Cell into Four Haploid Cells 772
Meiosis I Produces Two Haploid Cells That Have Chromosomes Composed of Sister Chromatids 773
Meiosis II Resembles a Mitotic Division 778
Defects in Meiosis Lead to Nondisjunction 779
Sperm and Egg Cells Are Generated by Meiosis Accompanied by Cell Differentiation 781
Meiotic Maturation of Oocytes is Tightly Regulated 782
25.3: Genetic Variability: Segregation and Assortment of Alleles 784
Meiosis Generates Genetic Diversity 784
Information Specifying Recessive Traits Can Be Present Without Being Displayed 784
Alleles of Each Gene Segregate from Each Other During Gamete Formation 785
Alleles of Each Gene Segregate Independently of the Alleles of Other Genes 786
Chromosome Behavior Explains the Laws of Segregation and Independent Assortment 787
The DNA Molecules of Homologous Chromosomes Have Similar Base Sequences 787
25.4: Genetic Variability: Recombination and Crossing Over 789
Chromosomes Contain Groups of Linked Genes That Are Usually Inherited Together 789
Homologous Chromosomes Exchange Segments During Crossing Over 789
Gene Locations Can Be Mapped by Measuring Recombination Frequencies 791
25.5: Genetic Recombination in Bacteria and Viruses 792
Co-infection of Bacterial Cells with Related Bacteriophages Can Lead to Genetic Recombination 792
Recombination in Bacteria Can Occur Via Transformation or Transduction 793
Conjugation Is a Modified Sexual Activity That Facilitates Genetic Recombination in Bacteria 793
25.6: Mechanisms of Homologous Recombination 796
DNA Breakage and Exchange Underlie Homologous Recombination Between Chromosomes 796
The Synaptonemal Complex Facilitates Homologous Recombination During Meiosis 796
Homologous Recombination Between Chromosomes Relies on High-Fidelity DNA Repair 797
Summary of Key Points 799
Problem Set 799
Human Connections: When Meiosis Goes Awry 780
Key Technique: Using Mendel’s Rules to Predict Human Disease 790
Chapter 26: Cancer Cells 802
26.1: How Cancers Arise 802
Tumors Arise When the Balance Between Cell Division and Cell Differentiation or Death Is Disrupted 803
Cancer Cell Proliferation Is Anchorage Independent and Insensitive to Population Density 804
Cancer Cells Are Immortalized by Mechanisms That Maintain Telomere Length 804
Defects in Signaling Pathways, Cell Cycle Controls, and Apoptosis Contribute to Cancer 804
Cancer Arises Through a Multistep Process Involving Initiation, Promotion, and Tumor Progression 805
26.2: How Cancers Spread 806
Angiogenesis Is Required for Tumors to Grow Beyond a Few Millimeters in Diameter 806
Blood Vessel Growth Is Controlled by a Balance Between Angiogenesis Activators and Inhibitors 807
Cancer Cells Spread by Invasion and Metastasis 808
Changes in Cell Adhesion, Motility, and Protease Production Promote Metastasis 808
Relatively Few Cancer Cells Survive the Voyage Through the Bloodstream 809
Blood Flow and Organ-Specific Factors Determine Sites of Metastasis 809
The Immune System Influences the Growth and Spread of Cancer Cells 810
The Tumor Microenvironment Influences Tumor Growth, Invasion, and Metastasis 810
26.3: What Causes Cancer? 811
Epidemiological Data Have Allowed Many Causes of Cancer to Be Identified 811
Many Chemicals Can Cause Cancer, Often After Metabolic Activation in the Liver 812
DNA Mutations Triggered by Chemical Carcinogens Lead to Cancer 812
Ionizing and Ultraviolet Radiation Also Cause DNA Mutations That Lead to Cancer 813
Viruses and Other Infectious Agents Trigger the Development of Some Cancers 814
26.4: Oncogenes and Tumor Suppressor Genes 815
Oncogenes Are Genes Whose Products Can Trigger the Development of Cancer 815
Proto-oncogenes Are Converted into Oncogenes by Several Distinct Mechanisms 815
Most Oncogenes Encode Components of Growth-Signaling Pathways 817
Tumor Suppressor Genes Are Genes Whose Loss or Inactivation Can Lead to Cancer 820
The RB Tumor Suppressor Gene Was Discovered by Studying Families with Hereditary Retinoblastoma 821
The p53 Tumor Suppressor Gene Is the Most Frequently Mutated Gene in Human Cancers 822
The APC Tumor Suppressor Gene Encodes a Protein That Inhibits the Wnt Signaling Pathway 823
Inactivation of Some Tumor Suppressor Genes Leads to Genetic Instability 824
Cancers Develop by the Stepwise Accumulation of Mutations Involving Oncogenes and Tumor Suppressor Genes 825
Epigenetic Changes in Gene Expression Influence the Properties of Cancer Cells 828
Summing Up: Carcinogenesis and the Hallmarks of Cancer 828
26.5: Diagnosis, Screening, and Treatment 829
Cancer Is Diagnosed by Microscopic and Molecular Examination of Tissue Specimens 830
Screening Techniques for Early Detection Can Prevent Cancer Deaths 830
Surgery, Radiation, and Chemotherapy Are Standard Treatments for Cancer 831
Using the Immune System to Target Cancer Cells 831
Molecular Targeting Can Attack Cancer Cells More Specifically Than Chemotherapy 834
Cancer Treatments Can Be Tailored to Individual Patients 834
Summary of Key Points 834
Problem Set 835
Key Technique: Targeting Molecules in the Fight Against Cancer 832
Human Connections: Molecular Sleuthing in Cancer Diagnosis 826
Appendix: Visualizing Cells and Molecules 837
Optical Principles of Microscopy 837
The Illuminating Wavelength Sets a Limit on How Small an Object Can Be Seen 837
Resolution Refers to the Ability to Distinguish Adjacent Objects as Separate from One Another 838
The Practical Limit of Resolution Is Roughly 200 nm for Standard Light Microscopes and 2 nm for Electron Microscopes 840
The Light Microscope 840
Compound Microscopes Use Several Lenses in Combination 840
Phase-Contrast Microscopy Detects Differences in Refractive Index and Thickness 841
Differential Interference Contrast (DIC) Microscopy Utilizes a Split Light Beam to Detect Phase Differences 842
Digital Microscopy Can Enhance Captured Images 843
Fluorescence Microscopy Can Detect the Presence of Specific Molecules or Ions Within Cells 844
Confocal Microscopy Minimizes Blurring by Excluding Out-of-Focus Light from an Image 846
Other Techniques Minimize Blurring by Exciting a Thin Strip of Fluorescent Molecules 848
Digital Deconvolution Microscopy Can Be Used to Generate Sharp Three-Dimensional Images After Acquisition 849
Optical Methods Can Be Used to Measure and Manipulate Macromolecules 850
Superresolution Microscopy Has Broken the Diffraction Limit 851
Specimen Preparation Often Involves Fixation, Sectioning, and Staining 852
The Electron Microscope 852
Transmission Electron Microscopy Forms an Image from Electrons That Pass Through the Specimen 852
Scanning Electron Microscopy Reveals the Surface Architecture of Cells and Organelles 854
Sample Preparation Techniques for Electron Microscopy 854
Ultrathin Sectioning and Staining Are Common Techniques in Transmission Electron Microscopy 854
Radioisotopes and Antibodies Can Localize Molecules in Electron Micrographs 856
Negative Staining Can Highlight Small Objects in Relief Against a Stained Background 856
Shadowing Techniques Use Metal Vapor Sprayed Across a Specimen’s Surface 856
Freeze Fracturing and Freeze Etching Are Useful for Examining Membranes 857
Stereo Electron Microscopy and 3-D Electron Tomography Allow Specimens to Be Viewed in Three Dimensions 858
Specimen Preparation for Scanning Electron Microscopy Involves Fixation but Not Sectioning 859
Other Imaging Methods 860
Scanning Probe Microscopy Reveals the Surface Features of Individual Molecules 860
CryoEM Bridges the Gap Between X-Ray Crystallography and Electron Microscopy 861
Answer Key to Concept Check and Key Technique Box Questions 862
Glossary 869
Photo, Illustration, and Text Credits 895
Index 901
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