Microsomes and Drug Oxidations (eBook)

Front Cover 1
Microsomes and Drug Oxidations 4
Copyright Page 5
Table of Contents 12
Participants 6
Preface 10
PART I: MORPHOLOGICAL AND BIOCHEMICAL CHARACTERISTICS OF MICROSOMES 16
CHAPTER 1. MICROSOMES, ENDOPLASMIC RETICULUM AND INTERACTIONS OF CYTOPLASMIC MEMBRANES 18
Introduction 18
Properties of Lipid and Biological Membranes 23
Endoplasmic Reticulum 25
Peroxisomes and Smooth E.R. 29
Synthesis and Transport of Lipoprotein Granules 31
Smooth Endoplasmic Reticulum and Golgi Apparatus 33
References 35
CHAPTER 2. SUBFRACTIONATION OF RAT LIVER MICROSOMES 56
Abstract 56
Introduction 57
Discussion 66
Acknowledgement 70
References 70
CHAPTER 3. A POSSIBLE ROLE OF THE ENDOPLASMIC RETICULUM IN THE REGULATION OF GENETIC EXPRESSION THE MEMBRON CONCEPT 74
References 92
CHAPTER 4. THE METABOLISM OF DRUGS BY SUBFRACTIONS OF HEPATIC MICROSOMES: THE CASE FOR MICROSOMAL HETEROGENEITY 96
Conclusion 103
References 105
PART II: ELECTRON TRANSFER COMPONENTS 108
CHAPTER 5. ORGANIZATION OF THE MICROSOMAL ELECTRON TRANSPORT SYSTEM 110
Discussion 118
References 119
Discussion 120
CHAPTER 6. CHARACTERIZATION OF TWO HEMOPROTEINS OF LIVER MICROSOMES 126
Spectral Properties of P-450 128
Concluding Remarks 140
Acknowledgment 141
References 141
Discussion 144
CHAPTER 7. CYTOCHROME P-450 REDUCTION IN LIVER MICROSOMES AND ITS RELATIONSHIP TO DRUG METABOLISM 148
Reduction of azo- and nitro- and tetrazolium compounds 149
Distribution of NADPH-dependent enzyme activities in microsomal subfractions 154
Role of Various Components of the Electron Transfer Systemin Species Variation in Hepatic Microsomal Drug Metabolism 156
Effect of Drug Substrates on Hepatic Microsomal Cytochrome P-450 Reduction by NADPH 
157 
References 163
Discussion 164
CHAPTER 8. FATTY ACID . - OXIDATION IN A SOLUBLE MICROSOMAL ENZYME SYSTEM CONTAINING P-450 166
Hemoprotein P-450 167
References 173
Discussion 175
CHAPTER 9. ENZYMATIC . -OXIDATION: STOICHIOMETRY OF THE REACTION CATALYZED BY THE INDUCIBLE ENZYME SYSTEM OF PSEUDOMONAS OLEOVORANS 182
References 186
CHAPTER 10. THE PROPERTIES OF A PURIFIED HEPATIC MICROSOMAL MIXED FUNCTION AMINE OXIDASE 188
Introduction 189
Experimental 189
Discussion 199
References 201
CHAPTER 11. A COMPARISON OF NADPH DEPENDENT REDUCTIVE CLEAVAGE AND N-DEMETHYLATION OF AMINOAZOBENZENE, MONOMETHYLAMINOAZO-BENZENE AND DIMETHYLAMINOAZOBENZENE BY CELL FREE PREPARATIONS FROM RAT LIVER 204
Results 207
Discussion 209
References 212
CHAPTER 12. OXYGEN REACTIONS IN MODEL SYSTEMS 214
References 231
CHAPTER 13. SIGNIFICANCE OF THE NIH SHIFT WITH RESPECT TO LIVER MICROSOME HYDROXYLATIONS 240
References 244
Discussion 246
CHAPTER 14. THE MICROSOMAL HYDROXYLATION OF ETHYLBENZENE STEREOCHEMICAL, INDUCTION AND ISOTOPIC STUDIES 254
Discussion 260
Acknowledgements 261
References 262
PART III: ALTERATIONS OF MICROSOMAL ENZYMES 264
CHAPTER 15. OVERALL BIOCHEMICAL EFFECTS OF DRUG INDUCTION ON LIVER 
266 
Acknowledgment 282
References 282
Discussion 285
CHAPTER 16. SPECIFICITY IN THE REGULATION OF THE 6ß- , 7a AND 16a-HYDROXYLATION OF TESTOSTERONE BY RAT LIVER MICROSOMES 294
Results 294
Summary 309
Acknowledgments 310
References 310
Discussion 311
CHAPTER 17. FORMATION OF A NEW P-450 HEMOPROTEIN AFTER TREATMENT OF RATS WITH POLYCYCLIC HYDROCARBONS 318
SKF 525-A Studies 320
Two-Substrate Kinetic Studies 321
Spectral Studies 
322 
Binding Studies 326
Thioacetamide Studies 332
Summary 339
Acknowledgement 340
References 341
Discussion 342
CHAPTER 18. SPECTROPHOTOMETRIC STUDIES OF CYTOCHROME P-450 OF LIVER MICROSOMES AFTER INDUCTION WITH PHENOBARBITAL AND 3-METHYLCHOLANTHRENE 
346 
References 358
Discussion 359
CHAPTER 19. THE EFFECTS OF 3-METHYLCHOLANTHRENE AND PHENOBARBITAL ON LIVER MICROSOMAL HEMOPROTEINS AND ON THE HYDROXYLATION OF BENZPYRENE 
364 
Discussion 374
References 377
Discussion 379
CHAPTER 20. SPECTRAL INVESTIGATIONS ON CYTOCHROME-P-450 386
References 400
Discussion 401
PART IV: DRUGS AND PROTEIN SYNTHESIS 402
CHAPTER 21. DRUGS AND MICROSOMAL ENZYME FORMATION IN VIVO AND IN MAMMALIAN CELL CULTURE 404
References 436
Discussion 441
CHAPTER 22. ACTIVATION OF CHROMATIN BY 3-METHYLCHOLANTHRENE 446
Introduction 446
Discussion 459
Acknowledgements 461
References 461
Discussion 464
CHAPTER 23. INDUCTION, STABILIZATION AND TURNOVER OF ENDOPLASMIC RETICULUM PROTEINS 468
Summary 468
References 484
Discussion 486
CHAPTER 24. EFFECT OF PHENOBARBITAL ON THE TURNOVER OF MICROSOMAL ENZYMES 490
Methods 491
Results and Discussions 492
References 506
Discussion 507
CHAPTER 25. THE ROLE OF HEME IN THE SYNTHESIS AND REPRESSION OF MICROSOMAL PROTEIN 510
Methods 511
Results and Discussion 512
Acknowledgement 523
References 524
Discussion 527
CHAPTER 26. INSECT MICROSOMES AND INSECTICIDE CHEMICAL OXIDATIONS 532
Introduction 532
Resistance 539
Summary 542
Acknowledgement 542
References 542
Discussion 545
CHAPTER 27. STIMULATORY EFFECT OF ACETONE ON THE ACTIVITY OF MICROSOMAL ANILINE PARA-HYDROXYLASE 548
Summary 548
Introduction 548
Materials and Methods 549
Results 549
Discussion 553
References 554
SUBJECT INDEX 556