Effect of natural phenols on the catalytic activity of cytochrome P450 2E1

被引：0
|
作者：
Mikstacka, R [1 ]
Gnojkowski, J [1 ]
Baer-Dubowska, W [1 ]
机构：
[1] Univ Med Sci, Dept Pharmaceut Biochem, PL-60780 Poznan, Poland
来源：
ACTA BIOCHIMICA POLONICA | 2002年 / 49卷 / 04期
关键词：
polyphenols; tannic acid; protocatechuic acid; resveratrol; CYP2E1; inhibition kinetics; mechanism-based 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：
The effect of protocatechuic acid, tannic acid and trans-resveratrol on the activity of p-nitrophenol hydroxylase (PNPH), an enzymatic marker of CYP2E1, was examined in liver microsomes from acetone induced mice. trans-Resveratrol was found to be the most potent inhibitor (IC50 = 18.5 0.4 muM) of PNPH, while protocatechuic acid had no effect on the enzyme activity. Tannic acid with IC50 = 29.6 +/- 3.3 muM showed mixed- and trans-resveratrol competitive inhibition kinetics (K-i = 1 muM and 2.1 muM, respectively). Moreover, trans-resveratrol produced a NADPH-dependent loss of PNPH activity, suggesting mechanism-based CYP2E1 inactivation. These results indicate that trans-resveratrol and tannic acid may modulate cytochrome P450 2E1 and influence the metabolic activation of xenobiotics mediated by this P450 isoform.
引用
收藏
页码：917 / 925
页数：9
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