Alcohol and Aldehyde Metabolizing Systems (eBook)

Front Cover 1
Enzymology and Subcellular Organelles 4
Copyright Page 5
Table of Contents 6
LIST OF PARTICIPANTS 12
PREFACE 18
CHAPTER 1. A COMPARISON OF THE ENZYMICALLY CATALYZED OXIDATION OF GLYCERALDEHYDE-3-PHOSPHATE AND LACTATE 20
I. INTRODUCTION 20
II. RESULTS AND DISCUSSION 22
III. ACKNOWLEDGEMENTS 31
IV. REFERENCES 33
CHAPTER 2. MECHANISM OF ACTION OF LIVER ALCOHOL DEHYDROGENASE 36
I. INTRODUCTION 37
II. RESULTS AND DISCUSSION 38
III. REFERENCES 49
CHAPTER 3. EXTRAPOLATION OF MECHANISM STUDIES ON GLYCERALDEHYDE-3-PHOSPRATE DEHYDROGENASE TO THE TREATMENT OF AVIAN MUSCULAR DYSTROPHY 52
I. INTRODUCTION 52
IV. REFERENCES 59
V. ACKNOWLEDGMENTS 60
CHAPTER 4. KINETICS AND MECHANISM OF ACTIVATED LIVER ALCOHOL DEHYDROGENASE 62
I. INTRODUCTION 62
II. DISCUSSION 63
Ill. ACKNOWLEDGEMENTS 69
IV. REFERENCES 69
CHAPTER 5. SOLVENT ISOTOPE EFFECTS IN THE YEAST ALCOHOL DEHYDROGENASE REACTION 72
I. INTRODUCTION 72
II. EXPERIMENTAL 73
III. RESULTS AND DISCUSSION 73
III. DISCUSSION OF MECHANISM OF DRUG ACTION 58
IV. REFERENCES 59
V. ACKNOWLEDGMENTS 60
CHAPTER 6. KINETICS AND MECHANISM OF ACTIVATED LIVER ALCOHOL DEHYDROGENASE 62
I. INTRODUCTION 62
II. DISCUSSION 63
Ill. ACKNOWLEDGEMENTS 69
IV. REFERENCES 69
CHAPTER 7. SOLVENT ISOTOPE EFFECTS IN THE YEAST ALCOHOL DEHYDROGENASE REACTION 72
I. INTRODUCTION 72
II. EXPERIMENTAL 73
III. RESULTS AND DISCUSSION 73
IV. ACKNOWLEDGEMENTS 79
V. REFERENCES 79
CHAPTER 8. KINETICS OF NATIVE AND CHEMICALLY ACTIVATED HUMAN LIVER ALCOHOL DEHYDROGENASES 82
I. INTRODUCTION 82
II. DISCUSSION 83
III. REFERENCES 88
CHAPTER 9. SUBSTRATE SPECIFICITY AND THE HYDROPHOBIC SITE OF LIVER ALCOHOL DEHYDROGENASE (L-ADH) 90
I. MATERIALS AND METHODS 91
II. RESULTS AND DISCUSSION 92
III. REFERENCES 96
CHAPTER 10. PROPERTIES OF HORSE LIVER ALCOHOL DEHYDROGENASE SS 98
I. INTRODUCTION 98
II. METHODS 99
III. RESULTS AND DISCUSSION 99
IV. ACKNOWLEDGEMENTS 103
V. REFERENCES 103
CHAPTER 11. ROOM AND LOW TEMPERATURE SPECTRAL IDENTIFICATION OF THE COBALT BINDINGS SITES IN LIVER ALCOHOL DEHYDROGENASE 106
I. INTRODUCTION 106
II. MATERIAL AND METHODS 107
III. RESULTS 108
IV. DISCUSSION 114
V. ACKNOWLEDGEMENTS 119
VI. ABBREVIATIONS 119
VII. REFERENCES 119
CHAPTER 12. HETEROGENEITY IN THE RAPIDLY EXCHANGING METALS OF HORSE LIVER ALCOHOL DEHYDROGENASE 122
I. INTRODUCTION 122
II. MATERIALS AND METHODS 123
III. RESULTS AND DISCUSSION 123
IV. REFERENCES 126
CHAPTER 13. MAGNETIC RESONANCE STUDIES OF THE INTERACTIONS OF IMIDAZOLE AND OTHER LIGANDS WITH COBALT SUBSTITUTED ALCOHOL DEHYDROGENASE FROM LIVER 128
I. INTRODUCTION 128
II. MATERIALS AND METHODS 129
III. RESULTS AND DISCUSSION 130
IV. CONCLUSIONS 135
V. ACKNOWLEDGEMENTS 135
VI. REFERERENCES 135
CHAPTER 14. WATER PROTON RELAXATION AND SPECTRAL STUDIES OF ALCOHOL DEHYDROGENASE PARTIALLY SUBSTITUTED WITH COBALT 138
I. INTRODUCTION 138
II. MATERIALS AND METHODS 138
III. RESULTS AND DISCUSSION 140
IV. ACKNOWLEDGEMENTS 141
V. REFERENCES 141
CHAPTER 15. INTERACTION AND ACTIVITIES OF NAD+ AND NAD+ ANALOGS WITH FOUR DEHYDROGENASES 142
I. INTRODUCTION 142
II. RESULTS 144
III. DISCUSSION 149
IV. REFERENCES 155
CHAPTER 16. MODIFICATION OF TRYPTOPHAN IN LIVER ALCOHOL DEHYDROGENASE 156
I. INTRODUCTION 156
II. INCORPORATION OF HNB 157
III. SPECTROSCOPIC STUDIES OF MODIFIED ENZYME 159
IV. PEPTIDE SEQUENCE STUDIES 159
V. EFFECTS OF HNB MODIFICATION ON STRUCTURE AND REACTIVITY 160
VI. ACKNOWLEDGEMENTS 161
VII. REFERENCES 161
CHAPTER 17. STRUCTURAL AND FUNCTIONAL CHANGES IN DIFFERENT ALCOHOL DEHYDROGENASES DURING EVOLUTION 164
1. INTRODUCTION 164
II. MATERIALS AND METHODS 165
III. RESULTS AND DISCUSSION 165
IV. GENERAL CONCLUSIONS 173
V. ACKNOWLEDGEMENT 173
VI. REFERENCES 174
CHAPTER 18. METAL ... EFFECTORS OF HORSE LIVER ALDEHYDE DEHYDROGENASES 176
I. INTRODUCTION 176
II. RESULTS AND DISCUSSION 178
III. CONCLUSIONS 184
IV. ACKNOWLEDGEMENTS 185
V. REFERENCES 185
CHAPTER 19. INTERACTION OF DISULFIRAM WITH HORSE LIVER ALDEHYDE DEHYDROGENASE 186
I. INTRODUCTION 186
III. RESULTS AND DISCUSSION 187
IV. CONCLUSIONS 191
V. ACKNOWLEDGEMENTS 192
VI. REFERENCES 192
CHAPTER 20. INTRACELLULAR LOCATION OF 3, 4-DIHYDROXYPHENYLACETALDEHYDE AND ACETALDEHYDE OXIDATION IN RAT LIVER 194
I. INTRODUCTION 194
II. RESULTS AND DISCUSSION 196
III. CONCLUSIONS 200
IV. ACKNOWLEDGEMENTS 201
V. REFERENCES 201
CHAPTER 21. LOCALIZATION AND PROPERTIES OF ALDEHYDE REDUCTASE 204
I. INTRODUCTION 204
III. REFERENCES 213
CHAPTER 22. HUMAN LIVER ALDEHYDE DEHYDROGENASE 214
I. INTRODUCTION 214
II. REFERENCES 221
III. ACKNOWLEDGEMENT 221
CHAPTER 23. INHIBITION OF RAT-LIVER ALDEHYDE DEHYDROGENASESIN VITRO AND IN VIVO BY DISULFIRAM, CYANAMIDE AND THEALCOHOL-SENSITIZING COMPOUND COPRINE 222
I. INTRODUCTION 222
II. MATERIALS AND METHODS 223
III. RESULTS AND DISCUSSION 224
IV. ACKNOWLEDGEMENTS 230
V. REFERENCES 231
CHAPTER 24. CORRELATION BETWEEN THE ACTIVITY OF ACETALDEHYDE DEHYDROGENASE AND THE STRUCTURE OF MITOCHONDRIA 232
I. INTRODUCTION 232
II. RESULTS AND DISCUSSION 233
III. ACKNOWLEDGEMENT 239
IV. REFERENCES 239
CHAPTER 25. INDUCTION1 OF CYTOSOLIC ALDEHYDE DEHYDROGENASE ISOZYMES: INFLUENCE ON ACETALDEHYDE METABOLISM 242
I. INTRODUCTION 242
II. METHODS 244
III. RESULTS AND DISCUSSION 245
IV. CONCLUSIONS 251
V. ACKNOWLEDGEMENT 252
VI. REFERENCES 252
CHAPTER 26. THE PLASTIC AND FLUID NATURE OF THE MITOCHONDRIAL ENERGY TRANSDUCING MEMBRANE 254
I. INTRODUCTION 254
II. DISCUSSION 256
III. CONCLUSIONS 276
IV. ACKNOWLEDGEMENTS 277
V. REFERENCES 277
CHAPTER 27. PEROXIDE GENERATION IN MITOCHONDRIA AND UTILIZATION BY CATALASE 280
I. DISCUSSION 280
II. SUMMARY 292
III. REFERENCES 292
CHAPTER 28. METABOLISM OF H2O2 AND FATTY ACIDS BY RAT LIVER PEROXISOMES: IMPLICATIONS FOR ETHANOL DETOXIFICATION 294
I. H2O2 METABOLISM 294
II. FATTY ACID OXIDATION 297
III. ROLE OF PEROXISOMES IN ETHANOL OXIDATION 301
IV. ACKNOWLEDGEMEOTS 306
CHAPTER 29. SOME EFFECTS OF AGING AND LIPID-LOWERING DRUGSON LIPID METABOLISM AND THE HEPATIC ENDOPLASMIC RETICULUM 310
I. INTRODUCTION: AGING, REPRODUCTIVE ACTIVITY AND ARTERIOSCLEROSIS 310
II. LIPID LEVELS IN MALE RATS 311
III. PLASMA LIPOPROTEINS OF YOUND ADULT AND RETIRED BREEDER RATS 311
IV. AGE-RELATED CHANGES IN HEPATIC FINE STRUCTURE 314
V. THE EFFECT OF OXANDROLONE ON SERUM AND LIVER OF MALE RATS 319
VI. SUMMARY 322
VII. ACKNOWLEDGEMENTS 323
VIII. REFERENCES 323
CHAPTER 30. ON THE QUESTION OF WHETHER CYTOCHROME P-450 CATALYZES ETHANOL OXIDATION: STUDIES WITH PURIFIED FORMS OF THE CYTOCHROME FROM RABBIT LIVER MICROSOMES 326
I. INTRODUCTION 326
II. RESULTS AND DISCUSSION 327
III. ACKNOWLEDGEMENT 340
IV. REFERENCES 340
CHAPTER 31. EVIDENCE FOR THE DIRECT INVOLVEMENT OF HEPATIC CYTOCHROME P450 IN ETHANOL METABOLISM 342
I. INTRODUCTION 342
III. ACETALDEHYDE QUANTITATION 343
IV. COMPARISON OF VARIOUS ASSAY METHODS FOR MEASURING ACETALDEHYDE 345
V. THE EFFECT OF ANTIBODIES TO CYTOCHROME P450 AND CYTOCHROME P448 ON MICROSOMAL ETHANOL METABOLISM 346
VI. ETHANOL METABOLISM BY THE RECONSTITUTED P450 SYSTEM 347
VII. ACKNOWLEDGEMENTS 352
VIII. REFERENCES 352
CHAPTER 32. ADVANTAGES OF GAS CHROMATOGRAPHIC DETERMINATION OF ACETALDEHYDE IN STUDIES WITH ETHANOL AND ARECONSTITUTED ENZYME SYSTEM CONTAINING ELECTROPHORETICALLY HOMOGENEOUS PHENOBARBITAL-INDUCIBLE CYTOCHROME P-450 FROM RABBIT LIVER MICROSOMES 354
REFERENCES 358
CHAPTER 33. RECONSTITUTION OF THE HEPATIC MICROSOMAL ETHANOL OXIDIZING SYSTEM (MEOS) IN CONTROL RATS AND AFTER ETHANOL FEEDING 360
I. INTRODUCTION 360
II. RECONSTITUTION OF MEOS WITH CYTOCHROME P-450,NADPH-CYTOCHROME C REDUCTASE AND PHOSPHOLIPID 361
III. DIFFERENTIATION OF CATALASE ACTIVITY FROM THE RECONSTITUTED MEOS 363
IV. DIFFERENTIATION OF ADH ACTIVITY FROM THE RECONSTITUED MEOS 363
V. EFFECT OF CHRONIC ETHANOL CONSUMPTION ON THE ACTIVITY OF THEAZIDE INSENSITIVE MICROSOMAL ETHANOL, PROPANOL AND BUTANOL OXIDIZING SYSTEM (MEOS) 363
VI. INDUCTION OF A NEW SPECIES OF MICROSOMAL PROTEIN (PRESUMABLY AN APO-PROTEIN OF CYTOCHROME P-450) AFTER CHRONIC ETHANOL CONSUMPTION 365
VII. EFFECT OF CHRONIC ETHANOL CONSUMPTION OF THE SUBSPECIES OF CYTOCHROME P-450 AS DEFINED BY CYANIDE TITRATION 365
VIII. RECONSTITUTION OF MEOS WITH CYTOCHROME P-450 FROM ETHANOLFED OR CONTROL RATS WITH CONTROL NADPH-CYTOCHROME C REDUCTASE AND SYNTHETIC L-a-DIOLEOYL LECITHIN 365
IX. RECONSTITUTION OF MEOS WITH NADPH-CYTOCHROME C REDUCTASE FROM ETHANOL FED OR CONTROL RATS WITH CONTROL CYTOCHROME P-450 AND SYNTHETIC L-a-DIOLEOYL LECITHIN 367
X. CONCLUSIONS 367
XI. ACKNOWLEDGEMENTS 368
XII. REFERENCES 368
CHAPTER 34. MICROSOMAL ELECTRON TRANSPORT REACTIONS: THE FORMATION AND UTILIZATION OF HYDROGEN PEROXIDE AS RELATEDTO ALCOHOL METABOLISM 370
REFERENCES 378
CHAPTER 35. STUDIES ON THE CHARACTERIZATION OF THE ENZYME COMPONENTS PARTICIPATING IN THE HEPATIC-MICROSOMAL OXIDATION OF ALIPHATIC ALCOHOLS 380
.. INTRODUCTION 381
II. RESULTS AND DISCUSSION 381
III. SUMl^RY 388
IV. FOOTNOTES 388
V. ACKNOWLEDGEMENTS 389
VI. REFERENCES 389
CHAPTER 36. QUANTITATION OF PATHWAYS RESPONSIBLE FOR NADPH-DEPENDENT METHANOL, ETHANOL, AND BUTANOL OXIDATION BY HEPATIC MICROSOMES 392
I. INTRODUCTION 392
II. METHODS 393
III. RESULTS AND DISCUSSION 394
IV. REFEP^NCES 398
CHAPTER 37. CATALASE AND ALCOHOL DEHYDROGENASE-MEDIATED OXIDATION OF ETHANOL IN HEPATIC MICROSOMES OF ACATALASEMIC MICE 400
I. INTRODUCTION 400
II. RESULTS AND DISCUSSION 401
III. REFERENCES 408
CHAPTER 38. ANALYSIS OF MITOCHONDRIAL AND MICROSOMALCYTOCHROMES IN HUMAN LIVER BIOPSY 412
I. INTRODUCTION 412
II. MATERIALS AND METHODS 413
III. RESULT 415
IV. DISCUSSION 419
V. ACKNOWLEDGEMENTS 420
VI. REFERENCES 421
CHAPTER 39. A NOVEL ROUTE FOR THE METABOLISM OF ETHANOL THE OXIDATION OF ETHANOL BY HYDROXYL FREE RADICALS
I. INTRODUCTION 422
II. DISCUSSION AND CONCLUSIONS 429
III. ACKNOWLEDGEMENTS 430
IV. REFERENCES 430
CHAPTER 40. FOLATE DEFICXENCY AND METHANOL POISONING IN THE RAT 432
II. INTRODUCTION 432
III. METHODS 434
IV. RESULTS 436
V. DISCUSSION 436
VI. ACKNOWLEDGEMENTS 437
VII. REFERENCES 437
CHAPTER 41. THE MONKEY AS A MODEL IN METHANOL POISONING 438
I. INTRODUCTION 438
II. METHODS 439
III. RESULTS 439
V. DISCUSSION 445
VI. ACKNOWLEDGEMENTS 446
Vll. REFERENCES 447
CHAPTER 42. METHANOL POISONING: ROLE OF FORMATE METABOLISM IN THE MONKEY 448
I. INTRODUCTION 448
II. RESULTS 449
III. DISCUSSION 457
IV. ACKNOWLEDGEjyiENTS 458
V. REFERENCES 459
CHAPTER 43. MITOCHONDRIAL INJURY IN EXPERIMENTAL CHRONIC ALCOHOLISM 460
I. INTRODUCTION 460
II. MATERIALS AND METHODS 461
III. RESULTS AND DISCUSSION 462
IV. CONCLUSIONS 466
V. ACKNOWLEDGEMENTS 468
VI. REFERENCES 468
INDEX 470