Further investigations of the metabolism of fluroxene and the degradation of cytochromes P-450 in vitro
| Autor: | Gillian A. Sapeika, Julia A. Marsh, Sharon A. Lucas, Jean J. Bradshaw, Kathryn M. Ivanetich, Laurence S. Kaminsky |
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| Rok vydání: | 1977 |
| Předmět: |
Male
Cytochrome Heme In Vitro Techniques Biochemistry Cytochrome P-450 Enzyme System medicine Animals Anaerobiosis Pharmacology Metyrapone biology Chemistry Metabolism Trifluoroethanol Articles Lipid Metabolism In vitro Peroxides Rats Kinetics Biodegradation Environmental Fluroxene Enzyme Induction Microsome biology.protein Microsomes Liver Phenobarbital Hepatic microsome Oxidation-Reduction medicine.drug Ethers |
| Zdroj: | AJNR Am J Neuroradiol |
| ISSN: | 0006-2952 |
| Popis: | The effects of inhibitors and of inducing agents for cytochromes P-450 on the fluroxene mediated destruction of cytochromes P-450 were investigated with hepatic microsomes from male rats in vitro and compared with the metabolism of fluroxene (2,2,2-trifluoroethyl vinyl ether) to 2,2,2-tri-fluoroethanol under similar conditions. The fluroxene mediated destruction of cytochromes P-450 and the metabolism of fluroxene are fully inhibited under totally anaerobic conditions. Carbon monoxide, SKF 525A and metyrapone fully inhibit the fluroxene mediated destruction of cytochromes P-450 and partially inhibit the metabolism of fluroxene to trifluoroethanol in microsomes from phenobarbital pretreated rats. The K m values for the destruction of cytochromes P-450 by fluroxene in vitro were calculated as 0.8, 3.3 and 1.5 mM for microsomes from phenobarbital induced, 3-methylcholanthrene induced and uninduced animals, respectively. V max values for 3-methylcholanthrene and phenobarbital induced microsomes (approximately 0.5 nmol cytochromes P-450 destroyed/mg microsomal protein/7 min) are elevated compared to uninduced microsomes (0.2 nmol cytochromes P-450 destroyed/mg microsomal protein/10 min). The K m value for the metabolism of fluroxene to trifluoroethanol in control microsomes of approximately 1.0 mM is unchanged following induction, and V max for the production of trifluoroethanol is increased relative to controls only in phenobarbital induced microsomes. It is concluded that the fluroxene mediated destruction of cytochromes P-450 appears to involve both cytochrome P-448 and cytochrome P-450 whereas the production of trifluoroethanol from fluroxene is catalyzed by cytochrome P-450 but not by cytochrome P-448. |
| Databáze: | OpenAIRE |
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