Channels, Carriers, and Pumps (eBook)

An Introduction to Membrane Transport

Thomas Litman, Wilfred D. Stein (Autoren)

eBook Download: PDF

2014 | 2. Auflage
422 Seiten
Elsevier Science (Verlag)
978-0-12-416583-0 (ISBN)

Infos

An introduction to the principles of membrane transport: How molecules and ions move across the cell membrane by simple diffusion and by making use of specialized membrane components (channels, carriers, and pumps). The text emphasizes the quantitative aspects of such movement and its interpretation in terms of transport kinetics. Molecular studies of channels, carriers, and pumps are described in detail as well as structural principles and the fundamental similarities between the various transporters and their evolutionary interrelationships. The regulation of transporters and their role in health and disease are also considered. - Provides an introduction to the properties of transport proteins: channels, carriers, and pumps - Presents up-to-date information on the structure of transport proteins and on their function and regulation - Includes introductions to transport kinetics and to the cloning of genes that code transport proteins - Furnishes a link between the experimental basis of the subject and theoretical model building

Wilfred Stein is the author of three previous books on membrane transport, the first appearing almost fifty years ago. He has edited numerous books and written some 180 papers on various aspects of membrane transport and especially transport kinetics. These papers, especially those written together with his colleague William Lieb, defined many of the concepts used today in discussing movement across cell membranes. More recently he has turned to the study of the kinetics of drugs used in cancer therapy and in the treatment of malaria. He has taught biochemistry, biophysics and physiology at the University of Manchester and the Hebrew University of Jerusalem and also at the Weizmann Institute in Israel. He is currently Emeritus Professor of Biophysics at the Hebrew University. He is married to a librarian and has four children and nine grandchildren.

Inhalt

Front Cover 1
Channels, Carriers, and Pumps 4
Copyright Page 5
Dedications 6
Contents 8
Preface to the First Edition 12
Preface to the Second Edition 14
List of Symbols 16
1 Structural Basis of Movement Across Cell Membranes 18
1.1 Membrane Structure: Electron Microscopy of Biological Membranes 18
1.2 Chemical Composition of Biological Membranes 20
1.2.1 Membrane Lipids 21
1.2.2 Membrane Proteins 22
1.2.3 Membrane Carbohydrates 22
1.3 Membrane Phospholipid Structures and Their Self-Assembly 23
1.4 Phase Transitions in Biological Membranes 24
1.5 Membrane Proteins: Their Structure and Arrangement 29
1.5.1 Proteins That Span the Membrane Only Once 30
1.5.2 Proteins That Span the Membrane More Than Once 31
1.6 Synthesis of Membrane Proteins 32
1.7 Quantitation of Membrane Dynamics 37
1.8 Traffic Across the Plasma Membrane 41
1.9 The Cell Membrane as a Barrier and as a Passage 49
Suggested Readings 50
General 50
Membrane Structure 50
Membrane Lipids 50
Liposomes 51
Membrane Proteins 51
Membrane Dynamics 51
Glycophorin 51
Lactose Permease 51
Hydropathy Plots 51
Membrane Protein Structure 52
Synthesis of Membrane Proteins 52
Endocytosis, Membrane Turnover 52
Clathrin-Coated Pits and Caveolae 52
Lipid Rafts 52
Cytoskeleton 53
2 Simple Diffusion of Nonelectrolytes and Ions 54
2.1 Diffusion as a Random Walk 54
2.2 The Electrical Force Acting on an Ion 63
2.3 Permeability Coefficients and Partition Coefficients 68
2.4 Measurement of Permeability Coefficients 73
2.5 Analysis of Permeability Data 79
2.6 The Membrane as a Hydrophobic Sieve 82
2.7 Osmosis and the Diffusion of Water 85
2.8 Comparison of Osmotic and Diffusive Flow of Water 90
Suggested Readings 96
General 96
Diffusion as a Random Walk 96
Chemical Potential 96
Electrical Potential 96
Flux Ratio Test 97
Permeability and Partition Coefficients 97
Measurement of Permeability Coefficients 97
NMR and ESR 97
Unstirred Layers 97
Plant Cell Permeabilities 97
Membrane as a Hydrophobic Sieve 97
Osmosis and the Diffusion of Water 97
Water Channels – The Aquaporins 97
Electroosmosis and Streaming Potential 97
3 Ion Channels Across Cell Membranes 98
3.1 The Gramicidin Channel 99
3.2 The Acetylcholine Receptor Channel 104
3.3 Conductances and Cross-Sectional Areas of Single Channels 107
3.4 An Experimental Interlude 114
3.4.1 Identification of Channels by Patch-Clamping 114
3.4.2 Measurements of Membrane Potential by Using Intracellular Microelectrodes or by Following Dye Distribution 117
3.5 Diffusion Potentials: Goldman–Hodgkin–Katz Equation 119
3.6 Regulation and Modulation of Channel Opening 123
3.6.1 The Potassium Channel of Sarcoplasmic Reticulum 123
3.6.2 Sodium and Potassium Channels of Excitable Tissue 125
3.6.3 The Cell-to-Cell Channel or Gap Junction 135
3.6.4 Regulation and Modulation of Some Other Channels 136
Suggested Readings 144
Internet Resources 144
General 144
Electrostatic (Born) Free Energy 144
Gramicidin Channel 144
Enzyme Kinetics 144
Acetylcholine Receptor 144
Cloning and Molecular Biology 145
Acetylcholine Receptor Structure 145
Ionic Diffusion 145
Ligand-gated Ion Channels 145
Charge Effects on Channel Conductance 145
Patch Clamping 145
Fluorescent Dyes 145
Goldman-Hodgkin-Katz Relation 146
Potassium Channels 146
Sodium Channels 146
Voltage-Gated Channels 146
Cell-to-Cell Channel 146
Calcium Channel 147
4 Carrier-Mediated Transport: Facilitated Diffusion 148
4.1 Inhibition of Mediated Transport Systems 149
4.2 Kinetics of Carrier Transport 153
4.2.1 The Zero-Trans Experiment 154
4.2.2 Competitive and Noncompetitive Inhibition of Transport 156
4.2.3 The Equilibrium Exchange Experiment 158
4.2.4 Stimulation of Transport by Trans Concentrations of Substrate 159
4.3 The Carrier Model 161
4.4 Valinomycin: An Artificial Membrane Carrier That Works by a Solubility-Diffusion Mechanism 162
4.5 Two Conformations of the Carrier 165
4.6 A Deeper Analysis of the Kinetics of Carrier Transport 166
4.6.1 Some Relations Between the Transport Parameters for the Different Experimental Procedures 167
4.6.2 Carrier Systems May Behave Asymmetrically 169
4.7 Electrogenic Aspects of Carrier Transport 169
4.8 Some Individual Transport Systems 175
4.8.1 GLUT4: The Insulin-Regulated Glucose Transporter 175
4.8.2 The Amino Acid Carriers 177
4.8.3 The Organic Cation Transporters: The OCTs 179
4.9 An Overall View of the Membrane Carriers 182
4.10 The Full Equation for Carrier Transport 190
Suggested Readings 194
General 194
Molecular Biology of Glucose Transporter 194
Kinetics of Carrier Transport 194
Valinomycin 194
Two Conformations of the Carrier 194
Electrogenic Aspects of Carrier Transport 195
Amino Acid Transporters 195
Organic Cation Transporters 195
Insulin Regulation of Glucose Transport 195
The Warburg Effect: Glucose Metabolism in Cancer and other Proliferating Cells 195
5 Coupling of Flows of Substrates: Antiporters and Symporters 196
5.1 Countertransport on the Simple Carrier 197
5.2 Exchange-Only Systems: The Antiporters 198
5.2.1 The Kinetics of Antiport 199
5.2.2 Slippage and Leakage in Coupled Transport Systems 202
5.2.3 Asymmetry of Antiporters 203
5.2.4 How the Stoichiometry of Substrate Binding Determines the “Intensity” of Concentration 203
5.2.5 Some Particular Antiporter Systems 204
5.2.5.1 The Na+/H+ Antiporter as a Transducer of Cell-to-Cell Signals 204
5.2.5.2 Role of the Na+/Ca2+ Antiporter in the Regulation of Intracellular Calcium 207
5.2.6 How the Structural Basis of the Antiporters Is Beginning to Be Elucidated 209
5.2.6.1 The Antiporter EmrE 209
5.2.6.2 The Sodium/Proton Antiporters 216
5.3 The Symporters, Cotransport Systems Where Two (or More) Substrates Ride Together in Symport on a Simple Carrier 222
5.3.1 Crane’s Gradient Hypothesis 224
5.3.2 V and K Kinetics in Cotransport 227
5.3.2.1 K Kinetics 227
5.3.2.2 V and K Kinetics 229
5.3.3 Cis and Trans Inhibition Between Cosubstrates as Tests of the Cotransport (Symport) Model 229
5.3.4 Stoichiometry of Symtransport 231
5.3.5 Electrogenic Aspects of Cotransport: The Equilibrium Potential of a Cotransport System 232
5.3.6 Some Individual Cotransporters Described 234
5.3.6.1 The Lactose and Melibiose Symporters of E. coli 234
5.3.6.2 Accumulation of a Neurotransmitter in Storage Granules 239
5.3.6.3 The Ubiquitous Na+ K+ 2Cl- Cotransporter 240
5.3.7 How the Structural Basis of the Symporters Is Beginning to Be Elucidated 243
5.3.7.1 LacY—The Lactose Permease of E. coli, the Lactose/Proton Symporter 243
5.3.7.2 The Sodium–Sugar Symporters and Their Homologs 250
The Rocking Bundle Model 259
Suggested Readings 259
General 259
Countertransport 259
Kinetics of Antiport 260
ADP/ATP Exchange 260
The Bacterial Proton/Multidrug Antiporters 260
Na+/H+ Antiporter 260
Growth Factors 261
Na+-Ca2+ Antiporter 261
Electrogenicity 261
Cotransport Systems 261
Stoichiometry of Cotransport 261
Melibiose Transport 262
Lactose Permease 262
Molecular Biology of the Sodium-Glucose Symporter 262
Amino Acid Cotransport 262
Na+-K+ - 2Cl- Cotransporter 262
Structural Basis of the Symporters 263
6 Primary Active Transport Systems 264
6.1 The Sodium Pump of the Plasma Membrane 264
6.1.1 The Function of the Sodium Pump 264
6.2 The Calcium Pump of Sarcoplasmic Reticulum 272
6.2.1 Structural Studies on the Calcium ATPase (SERCA1a) 276
6.2.2 Structural Studies on the Na+,K+-ATPase 281
6.2.2.1 A Comparison of the E2 and E1 Conformations of the N+,K+-ATPase 281
6.2.2.2 Functional Role of the ß-Chain 285
6.2.2.3 FXYD Subunits and Regulation 287
6.3 The Calcium Pump of the Plasma Membrane 290
6.4 The H+, K+-ATPase of Gastric Mucosa: The Proton Pump of the Stomach 294
6.4.1 The P-Type ATPases in the Context of Protein Evolution 296
6.5 The Rotary ATPases 299
6.5.1 Structure of the Rotary ATPases 300
6.5.2 Mechanism of Action of the F0F1-ATPases 304
6.6 The Vacuolar Proton-Activated ATPase 313
6.7 Bacteriorhodopsin: A Light-Driven Proton Pump 313
6.8 MDR—Drug Pumps 319
6.8.1 The Discovery of MDR 319
6.8.2 The ABC Superfamily 321
6.8.3 Topology 321
6.8.4 Function 326
6.8.5 ATPase Activity 331
6.8.6 Substrates and Inhibitors of P-gp—Clarification of Concepts 333
6.8.7 Catalytic Cycle of P-gp 338
6.8.8 Structure 340
Suggested Readings 342
General 342
Thermodynamics of Pumping 342
Sodium Pump 342
Calcium Pump of Sarcoplasmic Reticulum 343
Calcium Pump of Plasma Membrane 343
Gastric H+K+-ATPase 343
Multidrug Resistance 343
F0F1 ATPases 344
Vacuolar and Anion Pumps 344
Bacteriorhodopsin 344
7 Regulation and Integration of Transport Systems 346
7.1 Regulation of Cell Volume 347
7.1.1 How the Post–Jolly Equation (Relating Cell Volume, Cell Content, and the Pump-Leak Ratio, Together with the Donnan Di... 349
7.1.2 Short-Term Regulation of Cell Volume 356
7.1.2.1 RVD—A Process Activated by Cell Swelling 357
7.1.2.2 RVI—A Process Activated by Cell Shrinkage 358
Cotransport of Solutes and Water 361
Experimental Data 366
Molecular Dynamics Simulations 370
7.2 Integration of Transport Systems 373
7.2.1 Epithelia, with Special Reference to the Kidney 373
7.2.1.1 Morphology of Epithelia 373
7.2.1.2 Tight, Intermediate, and Leaky Epithelia 375
7.2.1.3 The Mammalian Kidney 378
7.2.1.4 The Transport System “Menu” 379
7.2.2 A Tight Epithelium: The Collecting Duct 382
7.2.3 An “Intermediate” Epithelium: The Thick Ascending Limb of the Mammalian Kidney 384
7.2.4 A Leaky Epithelium: The Proximal Tubule 386
7.2.5 Tight, Intermediate, and Leaky Epithelia Compared 390
7.2.6 The Control of Glucose Transport Across the Intestine 390
7.2.7 Transporters and the Control of Cell Migration 394
7.2.8 Vectorial Assembly and Sorting of Membrane Transport Systems in Epithelia 398
7.3 Channels of Death 400
Suggested Readings 408
General 408
Cell Volume: Long Term 408
Cell Volume: Short Term 408
Cotransport of Sugars, Salt and Water 408
Kidney Structure 408
Types of Epithelia 409
Transport System Menu 409
Intestinal Glucose Transport 409
Water Channels 409
Cell Migration and Cell Volume Control 409
Calcium Transport across Epithelia 409
Vectorial Assembly and Sorting 410
Apoptosis 410
Appendix: Fundamental Constants, Conversion Factors, and Some Useful Approximations 412
Fundamental Constants 412
Conversion Factors 412
Some Useful Approximations (for Back-of-the-Envelope Calculations) 413
Index 414

Produkt-Details

• Erscheint lt. Verlag: 9.12.2014
• Sprache: englisch
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Botanik
• Themenwelt: Naturwissenschaften ► Biologie ► Ökologie / Naturschutz
• Themenwelt: Technik
• ISBN-10: 0-12-416583-4 / 0124165834
• ISBN-13: 978-0-12-416583-0 / 9780124165830