Ethanol oxidation

Ethanol and related alcohols can be ingested as part of the diet and are formed by microorganisms in the intestinal tract. Ethanol oxidation to acetate occurs primarily in liver cells in a multistep process first described by Racker (1949). First, in the cytosol, ethanol is oxidized to acetaldehyde, with the formation of NADH. Second, in the mitochondrion, acetaldehyde is oxidized to acetate with the formation of NADH. Finally, acetate in the mitochondrion can be condensed with coenzyme A to form acetyl CoA. Polymorphisms in the enzymes catalyzing the first two steps are associated with variation in the efficiency of alcohol catabolism in human populations (Chen et al. 1999; Lange et al. 1976; Jornvall 1985). The molecular mechanism by which cytosolic acetaldehyde enters the mitochondrial matrix is not known (Lemasters 2007).<p>Cytosolic enzymes capable of oxidizing acetaldehyde to acetate have also been identified and characterized in vitro (Inoue et al. 1979) so a purely cytosolic pathway for ethanol oxidation to acetate and conversion to acetyl-CoA can be annotated. The role of this pathway in vivo is unclear, though limited attempts to correlate deficiencies in the cytosolic enzyme with alcohol intolerance have yielded suggestive data (Yoshida et al. 1989). Additional peroxisomal and microsomal pathways for the oxidation of ethanol to acetaldehyde have been described; their physiological significance is unclear and they are not annotated here.

乙醇及其相关醇类可作为饮食的一部分被摄入，并在肠道微生物的作用下形成。乙醇氧化为乙酸的过程主要发生在肝脏细胞中，这一多步骤过程最早由Racker（1949年）所描述。首先，在细胞质中，乙醇被氧化为乙醛，并生成NADH。其次，在线粒体中，乙醛被氧化为乙酸，并生成NADH。最后，线粒体内的乙酸可以与辅酶A缩合形成乙酰辅酶A。催化前两步反应的酶的多态性与人类群体中酒精代谢效率的变异性相关（Chen等，1999年；Lange等，1976年；Jornvall，1985年）。细胞质中乙醛进入线粒体基质的具体分子机制尚不清楚（Lemasters，2007年）。体外已鉴定并表征了能够将乙醛氧化为乙酸的细胞质酶（Inoue等，1979年），因此可以注释乙醇氧化为乙酸并转化为乙酰辅酶A的纯细胞质途径。尽管有有限的研究尝试将细胞质酶的缺陷与酒精不耐性相关联，但这一途径在体内的作用尚不明确（Yoshida等，1989年）。此外，还描述了将乙醇氧化为乙醛的过氧化物酶体和微粒体途径；它们的生理学意义尚不明确，故此处未予注释。