Thurman R G
Fed Proc. 1977 Apr;36(5):1640-6.
The pathways responsible for ethanol oxidation and the toxic results of its metabolism are reviewed. The predominant pathway for ethanol oxidation at low ethanol concentrations involves alcohol dehydrogenase. However, at high alcohol concentrations, up to 50% of ethanol uptake is 4-methylpyrazole-intensitive. Oxidation of ethanol under these conditions is associated with a change in the steady-stage concentration of catalase-H2O2. Based on recent evidence, we conclude that it is unnecessary to postulate that ethanol is oxidized directly via cytochrome P-450. Acetaldehyde production from ethanol via the microsomal subfraction can be accounted for by the combined activities of catalase-H2O2 and alcohol dehydrogenase. The metabolism of ehtanol via alcohol dehydrogenase produces a marked reduction in the hepatocellular NAD-NADH sytems. This reduction is indirectly responsible for the inhibition of glycolysis, gluconeogenesis, citric acid cycle activity, and fatty acid oxidation and may be related to some of the pathological effects observed following chronic consumption of alcohol. Attempts in inhibit alcohol dehydrogenase with alkylpyrazoles and activate catalase with substrates for peroxisomal H2O2-generating flavoproteins, while successful, may have limited applicability because of the native toxicity of the substrates themselves...
本文综述了乙醇氧化的途径及其代谢产生的毒性结果。在低乙醇浓度下，乙醇氧化的主要途径涉及乙醇脱氢酶。然而，在高乙醇浓度下，高达50%的乙醇摄取对4-甲基吡唑不敏感。在这些条件下，乙醇的氧化与过氧化氢酶-H2O2稳态浓度的变化有关。基于最近的证据，我们得出结论，无需假定乙醇直接通过细胞色素P-450氧化。通过微粒体亚组分由乙醇产生乙醛可由过氧化氢酶-H2O2和乙醇脱氢酶的联合活性来解释。通过乙醇脱氢酶进行的乙醇代谢会使肝细胞NAD-NADH系统显著减少。这种减少间接导致糖酵解、糖异生、柠檬酸循环活性和脂肪酸氧化受到抑制，并且可能与长期饮酒后观察到的一些病理效应有关。用烷基吡唑抑制乙醇脱氢酶以及用过氧化物酶体产生H2O2的黄素蛋白的底物激活过氧化氢酶的尝试虽然成功，但由于底物本身的固有毒性，其适用性可能有限……
