Takagi T, Alderman J, Lieber C S
Alcohol. 1985 Jan-Feb;2(1):9-12. doi: 10.1016/0741-8329(85)90005-9.
The relative importance of ADH and MEOS for ethanol oxidation in the liver has yet to be elucidated. The discovery of a strain of deermice genetically lacking ADH (ADH-) which can consume ethanol at greater than 50% of the rates seen in deermice having ADH (ADH+) suggested a significant role for non-ADH pathways in vivo. To quantitate contributions of the various pathways, we examined first the ethanol oxidation rates with or without 4-methylpyrazole in isolated deermice hepatocytes. 4-Methylpyrazole significantly reduced the ethanol oxidation in both ADH+ and ADH- hepatocytes. The reduction seen in ADH- cells can be applied to correct for the effect of 4-methylpyrazole on non-ADH pathways of ADH+ deermouse hepatocytes. After correction, non-ADH pathways were found to contribute 28% of ethanol metabolism at 10 mM and 52% at 50 mM. When using a different approach namely measurement of the isotope effect, MEOS was calculated to account for 35% at low and about 70% at high blood ethanol concentrations. Thus, we found that two different complementary approaches yielded similar results, namely that non-ADH pathways play a significant role in ethanol oxidation even in the presence of ADH.
抗利尿激素（ADH）和微粒体乙醇氧化系统（MEOS）在肝脏乙醇氧化中的相对重要性尚未阐明。发现一种基因上缺乏ADH的鹿鼠品系（ADH-），其消耗乙醇的速度比具有ADH的鹿鼠（ADH+）快50%以上，这表明非ADH途径在体内具有重要作用。为了量化各种途径的贡献，我们首先在分离的鹿鼠肝细胞中检测了有无4-甲基吡唑时的乙醇氧化速率。4-甲基吡唑显著降低了ADH+和ADH-肝细胞中的乙醇氧化。在ADH-细胞中观察到的降低可用于校正4-甲基吡唑对ADH+鹿鼠肝细胞非ADH途径的影响。校正后，发现非ADH途径在10 mM时对乙醇代谢的贡献为28%，在50 mM时为52%。当使用不同的方法即测量同位素效应时，计算得出MEOS在低血乙醇浓度下占35%，在高血乙醇浓度下约占70%。因此，我们发现两种不同的互补方法得出了相似的结果，即即使存在ADH，非ADH途径在乙醇氧化中也起着重要作用。
