CHI-ADH IS THE SOLE ALCOHOL-DEHYDROGENASE ISOZYME OF MAMMALIAN BRAINS - IMPLICATIONS AND INFERENCES
CHI-ADH IS THE SOLE ALCOHOL-DEHYDROGENASE ISOZYME OF MAMMALIAN BRAINS - IMPLICATIONS AND INFERENCES
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DOI：
10.1073/pnas.82.24.8369
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发表时间：
1985-12-01
影响因子：
11.1
通讯作者：
VALLEE, BL
中科院分区：
文献类型：
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作者：
BEISSWENGER, TB;HOLMQUIST, B;VALLEE, BL
第III类（. ch.）是人、马、牛、猿、犬和啮齿动物脑中唯一的乙醇脱氢酶（ADH），并且是第一个从人或其他脊椎动物的脑中鉴定、纯化和表征的。与来自人胎盘和肝脏的相应同工酶一样，从哺乳动物脑中纯化的ADH同工酶既不被固定化吡唑抑制，也不与其结合，并且它们仅非常弱地氧化乙醇（Km > 2.5M）。实际上，将它们归类为“乙醇脱氢酶”是不正确的。它们含有4 g-原子的锌/mol，结合2摩尔的NAD，并且容易氧化长链脂肪族和芳香族伯醇。这些发现似乎排除了ADH保护这些脊椎动物的大脑免受乙醇或其代谢产物影响的可能性，以及大脑可以从ADH监测的乙醇代谢中为大脑功能产生能量的可能性。因此，. chi. - ADH必须扮演一个完全不同但未知的角色。大脑中没有检测到任何乙醇脱氢酶的活性，只有假设这种酶已经进化和发展为该器官中乙醇解毒的保护机制，才能造成智力上的困境。ADH同工酶的组织和底物特异性可能会给他们的生理作用的新见解。
Class III (.chi.) is the only alcohol dehdyrogenase (ADH) in human, equine, bovine, simian, canine, and rodent brain and is the first to be identified, purified, and characterized from the brain of humans or other vertebrates. Like the corresponding isozymes from human placenta and liver, the .chi.-ADH isozymes purified from mammalian brain are neither inhibited by nor do they bind to immobilized pyrazole, and they oxidize ethanol only very poorly (Km > 2.5 M). Indeed, it would be incorrect to classify them as "ethanol dehydrogenases". They contain 4 g-atom of zinc/mol, bind 2 moles of NAD, and readily oxidize long-chain aliphatic and aromatic primary alcohols. These findings appear to exclude the possibilities that ADH protects the brain of these vertebrates against ethanol or its metabolic products and that the brain can generate energy for cerebral function from ADH-monitored ethanol metabolism. Thus .chi.-ADH must serve a totally different but as yet unknown role. The failure to detect any ethanol dehydrogenase activity in brain creates an intellectual dilemma only if it is assumed that such an enzyme has evolved and developed as a protective mechanism for ethanol detoxification in that organ, as has been assumed. Tissue and substrate specificities of ADH isozymes are likely to give new insight regarding their physiological roles.