大鼠和小鼠体内一种抗双香豆素的肝脏4-硝基喹啉1-氧化物（4NQO）硝基还原酶将4-硝基喹啉1-氧化物（4NQO）转化为4-羟基氨基喹啉1-氧化物。

Conversion of 4-nitroquinoline 1-oxide (4NQO) to 4-hydroxyaminoquinoline 1-oxide by a dicumarol-resistant hepatic 4NQO nitroreductase in rats and mice.

作者信息

Benson A M

机构信息

Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock 72205-7199.

出版信息

Biochem Pharmacol. 1993 Oct 5;46(7):1217-21. doi: 10.1016/0006-2952(93)90470-h.

DOI:10.1016/0006-2952(93)90470-h

PMID:8216372

Abstract

The product formed from 4-nitroquinoline 1-oxide (4NQO), a potent carcinogen, by the action of mouse NADH:4NQO nitroreductase NR-1 was directly identified as 4-hydroxyaminoquinoline 1-oxide (4HAQO) by high performance liquid chromatography analyses in two systems. In liver cytosols from both male and female mice, NADH:4NQO nitroreductase was the predominant enzyme catalyzing the reduction of 4NQO. Rat liver cytosol catalyzed the conversion of 4NQO to either 4HAQO or a glutathione conjugate depending upon coenzyme or cosubstrate availability. Whereas NAD(P)H:quinone reductase (NAD(P)H:(quinone acceptor) oxidoreductase; DT diaphorase; EC 1.6.99.2) was the predominant 4NQO reductase present in liver cytosol from Sprague-Dawley rats, dicumarol-resistant NADH:4NQO nitroreductase specific activities were comparable with those of mouse liver cytosols. A 4NQO nitroreductase from rat liver cytosol was separated from NAD(P)H:quinone reductase chromatographically and shown to have a strong preference for NADH and to be insensitive to inhibition by dicumarol.

摘要

通过在两个系统中进行高效液相色谱分析，由强效致癌物4-硝基喹啉1-氧化物（4NQO）在小鼠NADH：4NQO硝基还原酶NR-1作用下形成的产物被直接鉴定为4-羟基氨基喹啉1-氧化物（4HAQO）。在雄性和雌性小鼠的肝脏胞质溶胶中，NADH：4NQO硝基还原酶是催化4NQO还原的主要酶。大鼠肝脏胞质溶胶根据辅酶或共底物的可用性将4NQO转化为4HAQO或谷胱甘肽缀合物。虽然NAD（P）H：醌还原酶（NAD（P）H：（醌受体）氧化还原酶；DT黄递酶；EC 1.6.99.2）是存在于Sprague-Dawley大鼠肝脏胞质溶胶中的主要4NQO还原酶，但抗双香豆素的NADH：4NQO硝基还原酶的比活性与小鼠肝脏胞质溶胶的相当。通过色谱法从大鼠肝脏胞质溶胶中分离出一种4NQO硝基还原酶，并显示其对NADH有强烈偏好，且对双香豆素的抑制不敏感。