Cronholm T
Pharmacol Biochem Behav. 1983;18 Suppl 1:229-32. doi: 10.1016/0091-3057(83)90176-4.
Effects of ethanol on interconversion of cyclohexanol and cyclohexanone was studied in isolated hepatocytes. Oxidation and reduction catalyzed by alcohol dehydrogenase were markedly inhibited and stimulated, respectively. The changed ratio between the rates indicated that the ratio of NAD+ to NADH bound to alcohol dehydrogenase decreased several hundred times. This is much more than for the NAD+ system used by, e.g., lactate dehydrogenase, and deuterium from [1,1-2H2] ethanol was incorporated in cyclohexanol much more than in, e.g., lactate. These results indicate that the coenzyme bound to alcohol dehydrogenase is not equilibrated with free coenzyme. Thus, the dissociation of NADH might be rate-limiting for ethanol oxidation. Deuterium transfer from chiral [1-2H] ethanols and [2-2H] glycerol in hepatocytes indicated that cytosolic malate dehydrogenase and lactate dehydrogenase were not completely equilibrated, whereas there was no difference in the utilization of NADH formed at alcohol dehydrogenase and at glycerol-3-phosphate dehydrogenase. Fluxes in redox reactions during ethanol oxidation may be too high for equilibration of cytosolic dehydrogenases.
在分离的肝细胞中研究了乙醇对环己醇和环己酮相互转化的影响。由醇脱氢酶催化的氧化和还原分别受到显著抑制和刺激。速率变化的比率表明，与醇脱氢酶结合的NAD⁺与NADH的比率降低了数百倍。这比例如乳酸脱氢酶所使用的NAD⁺系统要大得多，并且来自[1,1-²H₂]乙醇的氘掺入环己醇中的量比例如乳酸中的要多得多。这些结果表明，与醇脱氢酶结合的辅酶与游离辅酶不平衡。因此，NADH的解离可能是乙醇氧化的限速因素。肝细胞中来自手性[1-²H]乙醇和[2-²H]甘油的氘转移表明，胞质苹果酸脱氢酶和乳酸脱氢酶并未完全平衡，而在醇脱氢酶和3-磷酸甘油脱氢酶处形成的NADH的利用没有差异。乙醇氧化过程中氧化还原反应的通量可能过高，以至于胞质脱氢酶无法达到平衡。
