Riassunto
P-450 has in common with our nation that it can call Phila delphia its hometown. Yet there are differences, too. The U. S. A. was born and named in this city. P-450 was first recog nized here -- an odd CO-combining pigment without family or func tion. Japanese workers identified it as an unusual member of the cytochrome family. Finally, in Philadelphia, its biological func tion was established and its growth to a global power initiated. Since discovery of its function as terminal oxidase of the 21-steroid hydroxylase system of adrenocortical microsomes, P-450 has proved to play the same role in a wide variety of other mixed function oxidase systems involved in biosynthesis and catabolism of specific cell or body components as well as in the metabolism of foreign substances entering organisms. P-450-like oxygenating enzymes appear to be fundamental cellular constituents in most forms of aerobic organisms. Activation of molecular oxygen and incorporation of one of its atoms into organic compounds as cata lyzed by P-450 enzymes are reactions of vital importance not only for biosynthesis and degradation of steroid hormones necessary for sustaining life, but also for metabolic activation or inactivation of foreign agents such as drugs, food preservatives and additives, insecticides and carcinogens. Moreover, P-450 linked enzyme sys tems can either be induced or suppressed by these agents with significant biological consequences.
Contenuti
Session I — Chairman, John Schenkman.- 1.- Partial Purification and Separation of Multiple Forms of Cytochrome P-450 and Cytochrome P-448 from Rat Liver Microsomes.- Biochemical Characterization of Highly Purified Cytochrome P-450 and Other Components of the Mixed Function Oxidase System of Liver Microsomal Membranes.- Immunochemical and Compositional Comparison of Cytochromes P-450cam of Pseudomonas putida and P-450LM of Phenobarbital-Induced Rabbit Liver Microsomes.- Immunochemical and Functional Similarities and Differences among Iron-Sulfur Proteins Involved in Mammalian Steroidogenesis.- General Discussion.- Peisach, Coon, Jerina, Schenkman, Levin, Peterson, Ballou, Kamin, Baron, Masters.- 2.- Comparison of the Induction Course, Biophysical Chemical Interactions and Photochemical Action Spectra of Pheobarbital- and 3-Methylcholanthrene-Induced Hepatic Microsomal P-450.- Cytochrome P-450 in the Activation and Inactivation of Carcinogens.- Effect of Cyclic AMP on the Phenobarbital Induced Increase in Cytochrome P-450 and Hypertrophy of the Endoplasmic Reticulum of the Rat Liver.- Evidence for the Activation of 3-Methylcholanthrene as a Carcinogen In Vivo and as a Mutagen In Vitro by P1-450 from Inbred Strains of Mice.- Increased Translation as a Result of Elevated Initiation Factor Activity after Administration of 3-Methylcholanthrene.- General Discussion.- Holtzman, Hutterer, Coon, Cooper, Schenkman, Jerina, Peisach, Remmer, Schleyer, Cinti, Nebert, Bresnick, Narasimhulu, Orrenius.- Session II: Chairman, Daniel Nebert.- 1.- Optical and EPR Studies of Partially Purified Rabbit Liver Cytochrome P-450.- Studies on the Spin State of 3-Methylcholanthrene-Induced Cytochrome P-450 from Rat Liver.- An Analysis of the Optical Titrations of the 430 and 455 nm Chromophores of Ethyl Isocyanide Complexes of Mammalian Hepatic Cytochrome P-450.- Implications of Ligand Modified Spectra of Cytochrome P-450 Associated with Pregnenolone Synthesis in Mitochondria from Corpus Luteum.- General Discussion.- Mannering, Witmer, Lu, Snyder, Levin, Nebert, Holtzman, Remmer, Vore, Narasimhulu, Stern, Kamin, Peisach, Schenkman, Hildebrandt, Coon.- 2.- Studies on the Interaction of Water with Microsomal Cytochrome P-450.- Drug Metabolism in Isolated Rat Liver Cells.- Role of Phospholipids in Adrenocortical Microsomal Hydroxylation Reactions: Activation of Lipid-Depleted Microsomal Preparations by Non-Ionic Detergents.- On the Structure of Putidaredoxin and Cytochrome P-450cam, and Their Mode of Interaction.- Metabolic Control of Cytochrome P-450cam.- General Discussion.- Stern, Peterson, Dus, Peisach, Bresnick, Orrenius, Holtzman, Remmer, Cinti, Thurman, Nebert, Narasimhulu, Coon, Lu, Jerina.- Session III — Chairman, Charlotte Witmer.- Relationship between Microsomal Hydroxylase and Glucuronyltransferase.- A Possible Role of Copper in the Regulation of Heme Biosynthesis through Ferrochelatase.- Mixed Function Oxidation and Intermediary Metabolism: Metabolic Interdependence in the Liver.- Dissociation of Microsomal Ethanol Oxidation from Cytochrome P-450 Catalyzed Drug Metabolism.- General Discussion.- van der Hoeven, Remmer, Mannering, Thurman, Coon, Vatsis, Orrenius, Schenkman, Kamin, Bresnick, Wagner, Hildebrandt, Thurman.- Session IV : Chairman, Otto Rosenthal.- Interaction between Microsomal Electron Transfer Pathways.- Role of Cytochrome b5 in the NADH Synergism of NADPH-Dependent Reactions of the Cytochrome P-450.- The Role of Cytochrome b5 in Cytochrome P-450 Enzymes.- Role of Cytochrome b5 in NADPH- and NADH-Dependent Hydroxylation by the Reconstituted Cytochrome P-450- or P-448-Containing System.- The Role of Cytochrome b5 in Mixed Function Oxidations: Effect on Microsomal Binding of the Hemoprotein on Hepatic N-Demethylations.- Comparison of Methods to Study Enzyme Induction in Man.- General Discussion.- Holtzman, Lu, Mannering, Kamin, Lichtenberger, Rosenthal, Hildebrandt, Schleyer, Narasimhulu, Orrenius, Schenkman, Levin, Sasame, Cinti, Lotlikar.- Contributors.- Author Index.
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