除草剂绿麦隆在人细胞色素P450 3A4作用下的代谢

Metabolism of the herbicide chlortoluron by human cytochrome P450 3A4.

作者信息

Mehmood Z, Kelly D E, Kelly S L

机构信息

Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, Sheffield University, UK.

出版信息

Chemosphere. 1995 Dec;31(11-12):4515-29. doi: 10.1016/0045-6535(95)00297-l.

DOI:10.1016/0045-6535(95)00297-l

PMID:8574549

Abstract

Studies were carried out to investigate the metabolism of herbicide chlortoluron in the microsomal fractions and whole cells of Saccharomyces cerevisiae expressing human cytochrome P450 3A4. Both whole cells and microsomal fractions of yeast expressing human cytochrome P450 3A4 exhibited a typical dithionite-reduced, CO-difference absorbance spectrum with maximum absorbance at 448 nm. Chlortoluron produced a type I binding spectrum with cytochrome P450 3A4 with a Ks value of 200 microM. Chlortoluron was metabolised into four metabolites; hydroxylated-N-monodemethylated, hydroxylated ring methylated, N-didemethylated and N-monodemethylated products. Chlortoluron metabolism was absolutely dependent on NADPH and no metabolism was observed in control transformants.

摘要

开展了多项研究，以调查除草剂绿麦隆在表达人细胞色素P450 3A4的酿酒酵母微粒体组分和全细胞中的代谢情况。表达人细胞色素P450 3A4的酵母全细胞和微粒体组分均呈现典型的连二亚硫酸盐还原型、CO差示吸收光谱，最大吸收峰位于448 nm。绿麦隆与细胞色素P450 3A4产生I型结合光谱，Ks值为200 microM。绿麦隆代谢生成四种代谢产物；羟基化-N-单去甲基化产物、羟基化环甲基化产物、N-双去甲基化产物和N-单去甲基化产物。绿麦隆的代谢绝对依赖于NADPH，在对照转化体中未观察到代谢现象。