PHENYTOIN 4-HYDROXYLATION BY RABBIT LIVER P450IIC3 AND IDENTIFICATION OF ORTHOLOGS IN HUMAN LIVER-MICROSOMES

被引：34

作者：

DOECKE, CJ ^{[1
]}

SANSOM, LN ^{[1
]}

MCMANUS, ME ^{[1
]}

机构：

[1] FLINDERS UNIV,SCH MED,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1990年 / 166卷 / 02期

关键词：

D O I：

10.1016/0006-291X(90)90889-U

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：

The ability of rabbit liver microsomes to 4-hydroxylate phenytoin to 5-(4-hydroxyphenyl)-5-phenylhydantoin was studied. No significant difference was observed between the capacity of control and rifampicin, phenobarbital, acetone, 2,3,7,8-tetrachlorodibenzo-p-dioxin and phenytoin induced rabbit liver microsomes to 4-hydroxylate phenytoin. In reconstitution experiments using six purified rabbit cytochromes P450 isozymes, only P450IIC3 was capable of 4-hydroxylating phenytoin whereas P450IA1, P450IA2, P450IIB4, P450IIIA6, and P450IVB1 were inactive. Further, anti-P450IIC3 IgG completely inhibited phenytoin 4-hydroxylase activity in rabbit liver microsomes. The above data suggest a major role for the constitutive isozyme P450IIC3 in phenytoin 4-hydroxylase activity in rabbit liver. In human liver microsomes P450IIC3 IgG inhibited phenytoin 4-hydroxylase activity by 66%, suggesting that an ortholog to rabbit P450IIC3 is in part responsible for this activity in man. © 1990.

引用

页码：860 / 866

页数：7

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