MECHANISM OF INHIBITION OF THE LIVER CYTOCHROME-P-450-DEPENDENT MONOOXYGENASE SYSTEM BY PERFLUOROCARBONS

被引:0
作者
OBRAZTSOV, VV [1 ]
GRISHANOVA, AY [1 ]
GUDKOVA, OV [1 ]
SHEKHTMAN, DG [1 ]
机构
[1] RUSSIAN ACAD MED SCI,INST CLIN & EXPTL MED,NOVOSIBIRSK,RUSSIA
关键词
PERFLUOROCARBONS; CYTOCHROME-P-450; MONOOXYGENASE REACTIONS; INHIBITION;
D O I
暂无
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Perfluorodecalin, an inducer of the liver monooxygenase system, forms an enzyme-substrate complex with cytochrome P-450 when added to microsomes as a submicron emulsion. The K(app) values for perfluorodecalin binding to cytochrome P-450 in microsomes isolated from the liver of control and phenobarbital-treated rats are 5 . 10(-5) M and 2.3 . 10(-6) M, respectively. Perfluorodecalin competitively inhibits binding of substrates to cytochrome P-450 and decreases rates of monooxygenase reactions. When an excess of inert (not interacting with cytochrome P-450) perfluorocarbon is added to microsomes, perfluorodecalin is extracted from the active center of cytochrome P-450. The simultaneous inhibition and induction of monooxygenase enzymes after administration of perfluorodecalin to rats cause considerable uncertainty concerning the rates of various monooxygenase reactions. The data are consistent with the hypothesis that constitutive forms of cytochrome P-450 act as primary receptors for xenobiotic inducers of phenobarbital-type cytochrome P-450 isoforms.
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页码:694 / 701
页数:8
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