The Enzymes of Biological Membranes (2^nd Ed., Softcover reprint of the original 1st ed. 1985)
Volume 3: Membrane Transport (SECOND EDITION)

In the first edition of The Enzymes of Biological Membranes. published in four volumes in 1976, we collected the mass of widely scattered information on membrane-linked enzymes and metabolic processes up to about 1975. This was a period of transition from the romantic phase of membrane biochemistry, preoccupied with conceptual developments and the general properties of membranes, to an era of mounting interest in the specific properties of membrane-linked enzymes analyzed from the viewpoints of modem enzymology. The level of sophistication in various areas of membrane research varied widely; the structures of cytochrome c and cytochrome b were known 5 to atomic detail, while the majority of membrane-linked enzymes had not even been isolated. In the intervening eight years our knowledge of membrane-linked enzymes ex­ panded beyond the wildest expectations. The purpose of the second edition of The Enzymes of Biological Membranes is to record these developments. The first volume describes the physical and chemical techniques used in the analysis of the structure and dynamics of biological membranes. In the second volume the enzymes and met­ abolic systems that participate in the biosynthesis of cell and membrane components are discussed. The third and fourth volumes review recent developments in active transport, oxidative phosphorylation and photosynthesis.

of Volume 3.- 27. The Energetics of Active Transport.- I. Introduction.- II. Thermodynamics of Protein-Ligand Interactions.- A. The Thermodynamic Box 3 · B. Intrinsic and Apparent Affinities 5.- III. Transport of the Simple Carrier-A Uni-Uni Isoenzyme.- A. Kinetics of the Simple Carrier 7 · B. Countertransport or Antiport-Coupling of Flows on the Simple Carrier 11.- IV. The CoTransport Systems-Iso Bi-Bi Enzymes.- A. The Fundamental Equation of Cotransport 19 · B. Maximizing the Effectiveness of the Cotransporter 19 · C. Apparent Affinities for a Cotransport System 23.- V. Primary Active Transport-Chemiosmotic Coupling.- A. Primary Active Transport vs. Secondary Active Transport 27 · B. The Kinetics of Primary Active Cotransport 28 · C. Maximizing the Effectiveness of the Primary Cotransporter 30 · D. Apparent Affinities of a Primary Cotransport System 30.- VI. Conclusions.- References.- 28. The Na+,K+-Transporting Adenosine Triphosphatase.- I. Introduction.- A. Definition 35 · B. Functions 35 · C. History 36.- II. Purification of the Na +,K +-ATPase.- A. Membrane-Bound Na+,K+-ATPase 38 · B. Soluble Na+,K+ATPase 39 · C. Criteria of Purity 39.- III. Cation Fluxes.- A. An Outline Scheme 40 · B. The Six Flux Modes 40 · C. Compatibility of the Pump Model with Steady-State Flux Kinetics 47.- IV. Catalytic Activities Not Associated with Ion Fluxes.- A. ATP-ADP Exchange 48 · B. Exchange of 18O between Orthophosphate and Water 49 · C. Phosphatase Activity 50.- V. Phosphorylation Studies.- A. Phosphorylation by ATP 52 · B. Phosphorylation by Orthophosphate 53 · C. Rephosphorylation of Newly Dephosphorylated Enzyme: Evidence for the Occlusion of K+ Ions 54 · D. Mechanism of Hydrolysis of Phosphoenzyme 54 · E. Kinetic Studies 55.- VI. Evidence for the Existence of Different Forms of the Dephosphoenzyme.- A. Differences in Reactivity to ATP and Orthophosphate 59 · B. Differences in Reactivity to Inhibitors 59 · C. Differences in Affinity for Nucleotides and Related Compounds 60 · D. Differences in the Pattern of Attack by Proteolytic Enzymes and in the Products of Proteolytic Digestion 61 · E. Differences in Intrinsic Fluorescence and in the Fluorescence of Probe Molecules 61 · F. Differences in Equilibrium Binding of Na+ and K+ Ions 65.- VII. The Existence and Role of Occluded-Ion Forms of the Na+,K+ATPase.- A. The Occluded-K+ Form of Dephosphoenzyme 67 · B. The Occluded-Na+ Form of Phosphoenzyme 70.- VIII. Structure of the Na+,K+-ATPase 71.- A. Number, Molecular Weight, and Ratio of Subunits 71 · B. Information from Electron Microscopy 72 · C. Structure of the ?-and ?-Subunits 73 · D. The Molecular Weight of Na+,K+-ATPase 75 · E. Is the Dimeric Nature of the Na+,K+-ATPase Relevant to Its Mechanism? 79 · F. The Role of Lipids 84.- IX. Inhibitors.- A. Cardiac Glycosides 85 · B. Vanadate 88 · C. Oligomycin 90 · D. Thimerosal 91.- X. Conclusion.- References.- 29. The Sarcoplasmic Reticulum Membrane.- I. Introduction.- II. Structure, Function, and Isolation of the Sarcotubular System.- III. Protein Composition of the Sarcoplasmic Reticulum Membrane.- IV. Ultrastructure and Asymmetry of the Sarcoplasmic Reticulum Membrane.- V. The ATPase of the Sarcoplasmic Reticulum Membrane.- A. Purification and Characterization of the ATPase 122 · B. Tryptic Fragments and Amino Acid Sequence of the ATPase 123 · C. ATPase-ATPase Interaction: An Oligomeric Form of the Enzyme 125 · D. Lipid-ATPase Interaction 128 · E. Reconstitution of the ATPase 132.- VI. Phosphorylation of Sarcoplasmic Reticulum Proteins.- VII. Calcium Release by the Sarcoplasmic Reticulum.- VIII. Cardiac Sarcoplasmic Reticulum Membrane.- IX. Biosynthesis of the Sarcoplasmic Reticulum Membrane.- A. Biosynthesis of Sarcoplasmic Reticulum in Vivo 140 · B. Biosynthesis of Sarcoplasmic Reticulum in Vitro 141 · C. Synthesis of Sarcoplasmic Reticulum Proteins in Cell-Free Systems 142.- X. Concluding Remarks.- References.- 30. Kinetic Regulation of Catalytic and Transport Activities in Sarcoplasmic Reticulum ATPase.- I. Introduction.- A. Ca2+ Uptake and ATP Hydrolysis 158 · B. Ca2+ Activation of SR ATPase 160.- II. Substrate Specificity.- A. Phosphorylated Enzymes Intermediate 165 · B. Calcium Translocation and Phosphoenzyme Cleavage 168 · C. Interconversion of the Ca2+-Binding Sites of High and Low Affinities 169 · D. The Ca2+-H+ Exchange 173 · E. Reversal of the Ca2+ Pump and Coupled ATPase 174 · F. Enzyme Phosphorylation in the Absence of a Transmembrane Ca2+ Gradient 177 · G. ATP Synthesis 179.- III. Conformational Changes.- IV. Conclusions.- References.- 31. Calcium-Induced Potassium Transport in Cell Membranes.- I. Introduction.- II. Characteristics of the Ca2+-Induced K+ Transport in Human Red Cells.- A. Calcium Homeostasis in Red Cells-Induction of Rapid K+ Transport 194 · B. Calcium Dependence and Activation Kinetics of K+ Transport 195 · C. Effects of Metal Ions 199 · D. Membrane Potential and Ca2+-Induced K+ Transport 200 · E. Effects of Cellular Components and Drugs 205.- III. Ca2+-Induced K+ Transport in Complex Cells.- A. Nonexcitable Cells 208 · B. Excitable Cells 212.- IV. The Molecular Basis of Ca2+-Induced K+ Transport.- A. The Transport Molecule(s): Biochemical Characteristics 219 · B. The Transport Molecule(s): Physical Characteristics 221.- V. Conclusions: The Prevalence and Significance of Ca2+-Induced K+ Transport.- References.- 32. Biochemistry of Plasma-Membrane Calcium-Transporting Systems.- I. Introduction.- II. The Ca2+-Pumping ATPase of the Plasma Membrane 236 A. The Enzyme in Situ 236 · B. The Purified Enzyme.- III. The Plasma Membrane Na+-Ca2+ Exchange.- References.- 33. The Calcium Carriers of Mitochondria.- I. Introduction.- II. The Ca2+ Uniporter.- A. The Driving Force for Ca2+ Accumulation 251 · B. The Molecular Nature of the Uniporter 253 · C. Factors Affecting Uniporter Activity 254.- III. The Na+-Ca2+ Carrier.- A. The Binding of External Substrate Cations 255 · B. The Binding of Internal Cations 256 · C. The Transport Mechanism 257 · D. The Dependence of the Na+-Induced Efflux of Ca2+ on the Mitochondrial Energy State 259 · E. Physiological Effectors of the Na+-Ca2+ Carrier 260 · F. Tissue Distribution 262.- IV. The Na+-Independent Release of Ca2+.- A. The Reaction Mechanism 263 · B. The Transport System 264 · C. Factors Affecting Activity of the Na+-Independent System 264 · D. Tissue Distribution 265.- V. The Resolution of the Component Fluxes of the Ca2+ Cycles.- A. Lanthanides 265 · B. Ruthenium Red 266 · C. Ca2+ Antagonists 266 · D. Other Distinctions 267.- VI. The Capacity of Isolated Mitochondria to Retain Accumulated Ca2+.- A. The Dependence of Ca2+-Induced Destabilization on Inorganic Phosphate and Redox State 267 · B. The Reversibility of Ca2+-Induced Destabilization 268 · C. The Effects of Adenine Nucleotides and Mg2+ 269.- VII. Ca2+ Recycling.- A. Properties of the Ca2+ Cycles 272 · B. Ca2+ Recycling in Heart Mitochondria 275 · C. Ca2+ Recycling in Liver Mitochondria 277.- VIII. Concluding Remarks.- References.- 34. Intestinal Phosphate Transport.- I. Introduction.- II. Intestinal Sites and Modes of Phosphate Absorption.- A. P, Transport in Small and Large Intestine 288 · B. Influence of Vitamin D 289 · C. Transepithelial P, Transport: Transcellular Pathways 289 · D. Transepithelial Pi Transport: Paracellular Pathway 295 · E. Absorption vs. Secretion 296.- III. Active Transport of Inorganic Phosphate across the Brush-Border Membrane.- A. Transmucosal Pi Transport in Intact Cells 298 · B. Na+-Gradient-Driven Pi Transport in Brush-Border Membrane Vesicles 299 · C. Attempts at Characterization of the P, Carrier 302.- IV. Hormonal Regulation of Intestinal Pi Transport.- A. Vitamin D 304 · B. Parathyroid Hormone and Cyclic AMP 308 · C. Calcitonin 309 · D. Glucocorticoids 309 · E. Insuli 310.- V. Intestinal Phosphate Absorption in Health and Disease.- A. Efficiency of Pi Absorption under Physiological Conditions 311 · B. Alteration of Phosphate Absorption in Human Disease 313.- References.- 35. Ion Transport in Nerve Membrane.- I. Introduction.- II. Methods for Transport Studies.- A. Introduction 322 · B. Isotopes 322 · C. Analytical Measurements 322 · D. Electrode Measurements 323 E. Optical Measurements 323.- III. Active Transport.- A. Introduction to Na Fluxes 323 · B. Na-Transport Systems 324 · C. Potassium Fluxes 326 · D. Chloride Transport 326 · E. Introduction to Calcium Transport 326 F. Magnesium Transport 329 · G. Hydrogen Ion Transport 331.- IV. Physiological Integration of Ion Fluxes.- References.- 36. The Molecular Basis of Neurotransmission: Structure and Function of the Nicotinic Acetylcholine Receptor.- I. Introduction.- II. Structural Aspects of the Acetylcholine Receptor.- A. Acetylcholine Receptor from Electric Organ 337 · B. Acetylcholine Receptor from Muscle 351 · C. Assembly and Degradation of Acetylcholine Receptors 353.- III. Functional Aspects of the Acetylcholine Receptor.- A. Electrophysiology of the Postsynaptic Membrane 360 · B. Pharmacology of the Nicotinic Acetylcholine Receptor 363.- IV. Structure-Function Correlations within the Acetylcholine Receptor Molecule: Reconstitution Studies as an Experimental Approach.- A. Reconstitution of Acetylcholine Receptors in Model Membranes 371 · B. Functional Studies of Acetylcholine Receptors after Reconstitution in Model Membranes 376.- V. Conclusions.- References.- 37. Structural Distinctions among Acetylcholinesterase Forms.- I. Introduction.- II. Asymmetric Acetylcholinesterase Forms Contain Collagen-like Tail Structures.- A. Acetylcholinesterase from Fish Electric Organs Provides a Structural Model for the Asymmetric Forms 405 · B. Asymmetric Acetylcholinesterase Forms in Other Tissues Have Hydrodynamic and Aggregation Properties Similar to the Electric Organ Forms 412 · C. Asymmetric Acetylcholinesterases Appear To Be Localized in the Extracellular Basement Membrane Matrix in Skeletal Muscle 413.- III. Globular Acetylcholinesterase Occurs as Soluble and Amphipathic Forms.- A. Human Erythrocyte Acetylcholinesterase Is an Amphipathic Form 415 · B. Comparison of Human Erythrocyte Acetylcholinesterase to Globular Acetylcholinesterases in Other Tissues That Bind Detergent 419.- IV. Relationships among Acetylcholinesterase Forms.- A. Acetylcholinesterase Forms in Rat Diaphragm 420 · B. Biosynthesis of Acetylcholinesterase Forms 423.- References.- 38. The Gastric H,K-ATPase.- I. Introduction.- II. Localization of the H,K-ATPase within the Parietal Cell.- III. Discovery of a Pathway for the Transport of K+ Salts in Membrane Vesicles Isolated from Secreting Tissues.- IV. Structure of the H,K-ATPase.- V. Catalytic Properties of the H,K-ATPase.- VI. Model.- VII. Comparison with Other Transport ATPases.- VIII. Problems and Future Research.- References.- 39. H+-Translocating ATPase and Other Membrane Enzymes Involved in the Accumulation and Storage of Biological Amines in Chromaffin Granules.- I. Introduction.- II. Isolation of Chromaffin Granules and Preparation of Chromaffin Ghosts.- III. The Composition of the Chromaffin Granule.- A. Membrane Proteins 451 · B. Soluble Proteins 454 · C. Lipids 455 · D. Storage Components 455 · E. Topography 456.- IV. The Electrochemical H+ Gradient.- A. Membrane Permeability to Ions 458 · B. Measurement of the ?pH 459 · C. Measurement of the ??, 461 · D. Measurement of the $$\Delta {{{\bar{\mu }}}_{{H + {\text{ }}}}}$$ 463.- V. The H +-Translocating ATPase.- A. Generation of a $$\Delta {{{\bar{\mu }}}_{{H + {\text{ }}}}}$$ 464 · B. Stoichiometry of H+/ATP 465 · C. Reversal of the ATPase 467 · D. Physicochemical Properties of the ATPase 467 · E. Isolation and Reconstitution 469.- VI. Amine Accumulation.- A. Physiochemical Properties 470 · B. Inhibitors 472 · C. Coupling to the $$\Delta {{{\bar{\mu }}}_{{H + {\text{ }}}}}$$ 472 · D. Net Accumulation of Biogenic Amines 478.- VII. The Electron-Transport Chain.- A. Organization 479 · B. Physicochemical Properties 481 · C. Physiologic Role 483.- VIII. Other Transport Systems.- A. ATP Accumulation 484 · B. Ascorbate Accumulation 485 · C. Calcium Accumulation 486.- IX. Conclusion: Biogenic Amine Transport into Other Organelles.- References.- 40. Hexose Transport and Its Regulation in Mammalian Cells.- I. Introduction.- A. Facilitative d-Glucose Transport 498 · B. Assay Methodology 500.- II. Human Erythrocyte d-Glucose Transport System.- A. Affinity Labeling 502 · B. Purification 503.- III. Regulation of the d-Glucose Transporter in Cultured Cells 504.- IV. Insulin Regulation of d-Glucose Transport Activity.- A. Insulin Binding and d-Glucose Transport Activation 506 · B. Insulinomimetic Agents 507 · C. Insulin-Receptor Aggregation 509 · D. Structural Relationships between the d-Glucose Transporter and Insulin Receptor 510 · E. Identification of the Insulin-Sensitive d-Glucose Transporter 511.- V. Mechanism of Insulin Activation of the d-Glucose Transporter.- VI. Summary and Conclusions.- References.- 41. The Bacterial Phosphoenolpyruvate:Sugar Phosphotransferase System.- I. Introduction.- II. Enzyme I.- III. HPr.- IV. IIIGlc.- A. Isolation and Characterization 530 · B. Kinetic Studies with IIIGlc533.- V. Sugar Receptor (II-B) Proteins.- A. Purification 537 · B. General Properties 538 · C. Organization of the Enzymes II-B in Membranes 540 · D. Exchange Transphosphorylation 540.- VI. Regulation of the PTS.- A. Introduction 542 · B. Regulation via Enzyme 1543 · C. Regulation via Acetate Kinase 543 · D. Regulation of the Activity of the Enzymes II 544 · E. Regulation of Methyl a-Glucoside Transport in Membrane Vesicles 546.- VII. PTS Regulation of Non-PTS Systems: PTS-Mediated Repression.- A. The crr and iex Genes 547 · B. crr Is the Structural Gene for IIIGlc 548 · C. Mechanism of Regulation of Non-PTS Transport Systems 550.- VIII. Prospectus.- References.- 42. The Maltose-Maltodextrin-Transport System of Escherichia coli K-12.- I. Introduction.- II. Maltose and Maltodextrin Catabolism in Escherichia coli K-12.- III. General Properties of Maltose and Maltodextrin Transport.- IV. Properties of the Individual Components.- A. The LamB Protein 564 · B. The Maltose-Binding Protein 566 · C. The MaIF and MaIK Proteins 566 · D. The MalG Protein 569.- V. Interactions between the Maltose-Binding Protein and the Membrane Components.- VI. A Model for the Operation of the Maltose-Maltodextrin-Transport System.- A. Transport across the Outer Membrane 571 · B. Transport across the Cytoplasmic Membrane 572.- References.- 43. Bacterial Amino-Acid-Transport Systems.- I. Introduction.- II. Classes of Transport Systems.- A. Multiplicity of Amino-Acid-Transport Systems 579 · B. Membrane-Bound Systems 585 · C. Periplasmic-BP-Dependent Systems 585.- III. Nature of Protein Components of BP-Dependent Transport Systems.- A. Periplasmic Components 587 · B. Membrane Components 588.- IV. Genetic and Physical Maps of the LIV-I and Histidine-Transport Genes.- V. Assembly of Transport Components.- VI. Energization and Reconstitution of Amino-Acid Transport.- A. Membrane-Bound, Osmotic-Shock-Resistant Systems: Energization and Reconstitution 594 · B. Energization of BP-Dependent Systems 595 · C. Reconstitution of BP-Dependent Amino-Acid Transport 596.- VII. Possible Models for Amino-Acid Transport.- VIII. Regulation of Amino-Acid Transport.- A. Regulation of the Histidine-Transport System 599 · B. Regulation of the LIV-I-Transport System 600 · C. Control of Membrane Protein Synthesis 602.- IX. Evolutionary Relationships among Periplasmic Systems.- References.- 44. The Iron-Transport Systems of Escherichia coli.- I. Types of Transport Systems in Escherichia coli.- A. Uptake through the Outer Membrane 617 · B. Uptake through the Cytoplasmic Membrane 618.- II. Peculiarities of the Iron-Transport Systems.- A. Requirement of Siderophores 619 · B. Receptor Proteins at the Cell Surface 622 · C. Functions of Genes Assigned to the Cytoplasmic Membrane; Release of Iron from the Siderophores; Modification of Siderophores 628 · D. The TonB and ExbB Functions 632 · E. Regulation of the Iron-Transport Systems 635.- III. Iron Supply and Virulence of Escherichia coli.- IV. Outlook.- References.- 45. Potassium Pathways in Escherichia coli.- I. Introduction.- II. Acquisition of Potassium-Free Cells: A Mechanical Disorganization of the Hydrophobic Continuum.- III. Potassium Uptake and Its Mechanochemical Switch.- IV. Potassium-Potassium Exchange: A Metabolism-Dependent, Energy-Independent Process.- V. The Effect of Thiol Reagents: A Reversible Opening of Potassium-Specific Channels.- VI. The K+ Channel is Specifically Controlled by Glutathione: It Is a GSH-Controlled Channel (GCC).- VII. Some Unsolved Problems.- References.