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大鼠肝脏可溶性部分和线粒体部分体系中的乙醇氧化。乙醛的调节作用。

Ethanol oxidation in systems containing soluble and mitochondrial fractions of rat liver. Regulation by acetaldehyde.

作者信息

Dawson A G

出版信息

Biochem Pharmacol. 1983 Jul 15;32(14):2157-65. doi: 10.1016/0006-2952(83)90221-6.

DOI:10.1016/0006-2952(83)90221-6
PMID:6347204
Abstract

Systems containing soluble fraction of rat liver, with or without mitochondrial fraction, oxidised [1-14C] ethanol to acetaldehyde, 14CO2 and non-volatile 14C-products of which acetate was the principal, and possibly the only, component. Ethanol oxidation was stimulated by pyruvate which served as an electron sink thereby allowing rapid regeneration of NAD. When no mitochondria were present acetaldehyde accumulated, rapidly at first but eventually reaching a plateau. The rate of ethanol oxidation in these systems was much lower than the measured maximum activity of alcohol dehydrogenase (ADH) and it was concluded that ADH was inhibited by the accumulated acetaldehyde. Mitochondria, because of their relatively high aldehyde dehydrogenase (ALDH) activity, prevented the accumulation of acetaldehyde, or quickly removed acetaldehyde already accumulated. This action was accompanied by a sharp increase in the rate of ethanol oxidation, presumably due to the deinhibition of ADH. Cyanamide, an inhibitor of mitochondrial ALDH, blocked the stimulatory effect of mitochondria on ethanol oxidation. It was concluded that, in the reconstituted systems, acetaldehyde played a dominant role in controlling the rate of ethanol oxidation. The possible importance of acetaldehyde in governing ethanol oxidation in vivo is discussed.

摘要

含有大鼠肝脏可溶部分的体系,无论有无线粒体部分,均可将[1-14C]乙醇氧化为乙醛、14CO2和非挥发性14C产物,其中乙酸盐是主要成分,也可能是唯一成分。丙酮酸可刺激乙醇氧化,它作为电子受体,从而使NAD得以快速再生。当不存在线粒体时,乙醛会积累,起初迅速积累,但最终会达到平稳状态。这些体系中乙醇氧化的速率远低于所测得的醇脱氢酶(ADH)的最大活性,由此得出结论,ADH受到积累的乙醛的抑制。线粒体因其相对较高的醛脱氢酶(ALDH)活性,可防止乙醛积累,或迅速清除已积累的乙醛。这一作用伴随着乙醇氧化速率的急剧增加,推测这是由于ADH的去抑制作用所致。氰胺是线粒体ALDH的抑制剂,它可阻断线粒体对乙醇氧化的刺激作用。得出的结论是,在重构体系中,乙醛在控制乙醇氧化速率方面起主导作用。文中还讨论了乙醛在体内调控乙醇氧化方面可能的重要性。

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