Metabolism of acetaldehyde to acetate by rat hepatic P-450s: Presence of different metabolic pathway from acetaldehyde dehydrogenase system
Metabolism of acetaldehyde to acetate by rat hepatic P-450s: Presence of different metabolic pathway from acetaldehyde dehydrogenase system
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DOI：
10.1111/j.1530-0277.1996.tb01721.x
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发表时间：
1996-02-01
影响因子：
3.2
通讯作者：
Monna, T
中科院分区：
文献类型：
--
作者：
Kunitoh, S;Asai, H;Monna, T
通过使用离子交换柱测定 [C-14] 乙醛产生的 [C-14] 乙酸，研究了微粒体中乙醛氧化的 NADPH 依赖性活性。大鼠肝微粒体在 NADPH 存在下表现出乙醛氧化活性。通过用乙醇处理大鼠，这种活性被诱导了两倍。我们将这种 NADPH 依赖性氧化系统命名为微粒体乙醛氧化系统（MAOS），以区别于线粒体和细胞质中乙醛的 NAD 依赖性乙醛氧化系统。我们进一步研究了促进 MAOS 活性的必需酶。在重构系统中研究了八种形式的纯化 P-450 的乙醛氧化活性。细胞色素 P-450 (CYP) 2E1 具有最高的氧化活性，CYP1A2 和 CYP4A2 具有次高的活性。其他形式的活性较低。为了评估这些形式对 MAOS 活性的贡献，进行了免疫印迹。乙醇处理可诱导 CYP2E1 增加 2 倍，但 CYP1A2 和 CYP4A2 则不会，这反映了乙醇处理增加了 MAOS 活性。这些结果表明CYP2E1是大鼠MAOS中的必需酶。
NADPH-dependent activity of acetaldehyde oxidation was investigated in microsomes by assaying [C-14]acetic acid produced from [C-14]acetaldehyde with ion-exchange column. Rat hepatic microsomes exhibited acetaldehyde oxidation activity in the presence of NADPH. This activity was induced 2-fold by the treatment of rats with ethanol. We designated this NADPH-dependent oxidation system as microsomal acetaldehyde-oxidizing system (MAOS), to distinguish from the NAD-dependent acetaldehyde oxidation system by acetaldehyde in mitochondria and cytsol. We further investigated essential enzymes contributing to MAOS activity. Acetaldehyde oxidation activity was investigated in eight forms of purified P-450 in a reconstituted system. Cytochrome P-450 (CYP) 2E1 had the highest oxidation activity and CYP1A2 and CYP4A2 had the next highest activity. Other forms had low activity. To assess the contribution of these forms to MAOS activity, immunoblot was done. CYP2E1 was induced 2-fold by ethanol treatment, but CYP1A2 and CYP4A2 were not, reflecting the MAOS activity increased by ethanol treatment. These results suggest that CYP2E1 is the essential enzyme in the MAOS of rats.