Inhibition of human cytochrome P450 3A4 activity by zinc(II) ion

被引：7
作者：
Kim, JS
Yun, CH [1 ]
机构：
[1] Chonnam Natl Univ, Hormone Res Ctr, Kwangju 500757, South Korea
[2] Paichai Univ, AngioLab, Taejon 302735, South Korea
[3] Chonnam Natl Univ, Sch Biol Sci & Technol, Kwangju 500757, South Korea
来源：
TOXICOLOGY LETTERS | 2005年 / 156卷 / 03期
关键词：
cytochrome P450 3A4; Zn(II) ion; NADPH-cytochrome P450 reductase; cytochrome b(5); testosterone 6 beta-hydroxylation activity;
D O I：
10.1016/j.toxlet.2004.12.006
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
Effects of Zn2+ on the activity and conformation of cytochorome P450 3A4 (CYP3A4) were investigated. Zn2+ specifically inhibited the testosterone 6 beta-hydroxylation activity of CYP3A4 with an IC50 value of 27 mu M. Zn2+ inhibited the CO-binding spectra of CYP3A4 reduced by NADPH-cytochrome P450 reductase (CPR) and NADPH only in the presenceof b(5).Zn2+-induced conformational changes of CYP3A4 were monitored by CD and intrinsic fluorescence. Zn2+ showed no significant effects on the activity of CYP3A4 supported by tert-butyl hydroperoxide, an oxygen surrogate, and on the reduction of b(5) by CPR and NADPH. These results suggest that the inhibitory effects of Zn2+ come from preventing the stimulation of b(5) on CYP3A4 activity. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
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页码：341 / 350
页数：10
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