Alderman J A, Sanny C, Gordon E, Lieber C S
Alcohol. 1985 Jan-Feb;2(1):91-5. doi: 10.1016/0741-8329(85)90022-9.
Depressed hepatic aldehyde dehydrogenase (ALDH) activity levels have been observed in alcoholics, but whether the deficit is primary or secondary in nature remains controversial. In this study, we examined liver ALDH in rodent (rat) and primate (baboon) animal models pair-fed nutritionally adequate ethanol or isocaloric carbohydrate containing liquid diets. Both species show qualitative changes in ALDH isozymes after ethanol consumption. The changes include alterations in isozyme patterns seen upon electrofocusing and decreased responsiveness to the ALDH inhibitor, disulfiram. The subcellular locus of most of the changes is cytosolic in the baboon and mitochondrial in the rat. Study of partially purified (enriched) baboon cytosolic ALDH confirmed changes seen in the original cytosols and kinetic characterization of the enriched enzyme revealed a 9-fold higher Km for acetaldehyde in ALDH from an ethanol treated animal. We note that qualitative and quantitative changes secondary to ethanol treatment in the primate model closely parallel those described in human alcoholics.
在酗酒者中观察到肝脏乙醛脱氢酶（ALDH）活性水平降低，但这种缺陷本质上是原发性还是继发性仍存在争议。在本研究中，我们在啮齿动物（大鼠）和灵长类动物（狒狒）模型中检测肝脏ALDH，这些动物成对喂养营养充足的乙醇或等热量含碳水化合物的流质饮食。两种动物在摄入乙醇后ALDH同工酶均出现定性变化。这些变化包括等电聚焦时同工酶模式的改变以及对ALDH抑制剂双硫仑的反应性降低。大部分变化的亚细胞定位在狒狒中是胞质的，在大鼠中是线粒体的。对部分纯化（富集）的狒狒胞质ALDH的研究证实了在原始胞质溶胶中观察到的变化，对富集酶的动力学表征显示，来自乙醇处理动物的ALDH中乙醛的米氏常数（Km）高9倍。我们注意到，灵长类动物模型中乙醇处理后的定性和定量变化与人类酗酒者中描述的变化非常相似。
