EVIDENCE FOR COMPLEXATION OF P-450 IIC6 BY AN ORPHENADRINE METABOLITE

被引：14

作者：

REIDY, GF

MURRAY, M

机构：

[1] Liver Research Unit, Department of Medicine, University of Sydney, Westmead

来源：

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

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/0006-291X(90)90876-O

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：

Removal of the orphenadrine metabolite from its complex with rat liver P-450 IIB1 is associated with a discrepancy in the reactivation of IIB1 activity. Two possible explanations are that either (1) NADPH-P-450-reductase is inaccessible to the restored IIB1, or (2) complexation of other P-450s may occur. Exogenous P-450 reductase increased all pathways of steroid hydroxylation (1.9 to 3.6-fold) but did not enhance reactivation of IIB1-dependent steroid 16β-hydroxylation. Instead, P-450 IIC6-dependent progesterone 21-hydroxylase activity was increased after dissociation to 122% of control. IIC6 activity was also inhibited in vitro in microsomes from phenobarbital-induced rats (ki = 151 μM). Thus, orphenadrine appears to complex P-450 IIC6 as well as IIB1 in rat liver. © 1990.

引用

页码：772 / 779

页数：8

共 19 条

[1]

BAST A, 1983, RES COMMUN CHEM PATH, V40, P391

[2] SPECTRAL INTERACTION OF ORPHENADRINE AND ITS METABOLITES WITH OXIDIZED AND REDUCED HEPATIC-MICROSOMAL CYTOCHROME-P-450 IN THE RAT [J].