The induction and competitive inhibition of a high affinity microsomal nitrosodimethylamine demethylase by ethanol.
The induction and competitive inhibition of a high affinity microsomal nitrosodimethylamine demethylase by ethanol.
复制标题
乙醇对高亲和力微粒体亚硝基二甲胺脱甲基酶的诱导和竞争性抑制。
作者：
Renxiu Ping;Y. Y. Tu;Chung S. Yang
本文研究了乙醇对大鼠肝微粒体代谢亚硝胺的影响。用含10%或15%乙醇的饮用水处理大鼠3天，导致微粒体N-亚硝基二甲胺脱甲基酶（NDMAd）活性增加4- 5倍，总P-450含量增加40-60%。增强主要是由于诱导的低Km形式（Km = 0.07 mM）的NDMAd。该处理诱导分子量在50000和52000之间的蛋白质种类，其中一些被认为是对NDMA具有高亲和力的P-450同工酶。除NDMA外，用乙醇处理还增强N-亚硝基-N-甲基乙胺、N-亚硝基甲基苯胺和N-亚硝基-N-甲基苄胺的代谢。当添加到孵育混合物中时，乙醇及其同系物抑制微粒体对这些亚硝胺的脱甲基作用。乙醇是低Km NDMAd的竞争性抑制剂，Ki为0.31 mM，在抑制亲脂性更高的亚硝胺代谢方面效果较差。
The effects of ethanol on the metabolism of nitrosamines by rat liver microsomes have been studied. Treatment of rats with 10 or 15% ethanol in drinking water for 3 days causes a 4- to 5-fold enhancement in microsomal N-nitrosodimethylamine demethylase (NDMAd) activity and a 40-60% increase in gross P-450 content. The enhancement is mainly due to the induction of a low Km form (Km = 0.07 mM) of NDMAd. The treatment induces protein species with molecular weights between 50000 and 52000, some of which are believed to be P-450 isozymes with high affinity to NDMA. In addition to NDMA, treatment with ethanol also enhances the metabolism of N-nitroso-N-methylethylamine, N-nitrosomethylaniline, and N-nitroso-N-methylbenzylamine. When added to the incubation mixture, ethanol and its homologs inhibit the demethylation of these nitrosamines by microsomes. Ethanol is a competitive inhibitor of the low Km NDMAd with a Ki of 0.31 mM and is less effective in inhibiting the metabolism of more lipophilic nitrosamines.