SEQUENTIAL OXIDATION OF ALCOHOLS BY ALCOHOL DEHYDROGENASE

乙醇脱氢酶（ADH）是生物合成的关键酶， 酶学的发展和广泛的应用。 肝 ADH一直是研究的主要焦点，并显示出广泛的 底物特异性，将醇类从甲醇氧化为甾体。 它们还具有将醛氧化成酸的能力。 这 活动没有得到广泛承认，虽然有零星的 相关现象的文献报道。 普遍的看法是， 然而，报告的醛和醛的动力学值 氧化和醛歧化阻止了生理 这种反应的相关性。 马肝醇脱氢酶 （HL-ADH）不仅能够氧化醛作为一种有趣的， 虽然非生理学副反应;但当在 在不掩盖这项活动的条件下，它完全有能力 用催化剂催化脂肪醛氧化成酸 其催化效率可与其催化剂相比，甚至更高， 醇氧化 我们的重点是详细的动力学研究， 确定反应的动力学值，目标是 将实验结果与总体动力学方案拟合。 这 由于意外的额外动力， 复杂性，我们已经发现，由于需要处理这两个 醛、游离醛和偕二醇水合物的形式， 不同的化合物 我们还在进一步制定方法， 允许监测酒精分解的全方位反应 可以进行。 虽然我们目前的重点仍然是动力学研究， 我们正在探索一项广泛倡议的可能性， ADH同工酶的序列异质性及其对 结构、功能和生理作用。 的资源 计算机图形实验室对于进行 结构评价。

The alcohol dehydrogenases (ADHs) have been pivotal to the development of enzymology and have widespread applications. Liver ADHs have been the primary focus of investigations and show broad substrate specificity, oxidizing alcohols from methanol to steroids. They also have the ability to oxidize aldehydes to acids. This activity is not widely recognized, although there have been sporadic reports in the literature of related phenomena. The prevailing view, however, is that the reported kinetic values for both aldehyde oxidation and aldehyde dismutation preclude the physiological relevance of this reaction. Horse liver alcohol dehydrogenase (HL-ADH) is not just able to oxidize aldehydes as an intriguing, albeit nonphysiological side reaction; but when assayed under conditions that do not obscure this activity, it is fully competent to catalyze the oxidation of aliphatic aldehydes to acids with catalytic efficiencies comparable to and even much greater than its catalysis of alcohol oxidation. Our focus is on detailed kinetic studies to determine the kinetic values for the reactions with the goal of fitting the experimental results to an overall kinetic scheme. This goal has been elusive because of the unanticipated extra kinetic complexity we have discovered due to the necessity of treating the two forms of aldehyde, the free aldehyde and the gemdiol hydrate as distinct compounds. We are also further developing methodology to allow monitor the full range of reactions that alcohol dehydrogenases can conduct. While our current focus has remained on kinetic studies, we are exploring the potential for a broad initiative to assess the sequence heterogeneity in ADH isozymes and the impact that has on the structure, function, and physiological effects. The resources of the Computer Graphics Laboratory are essential for conducting the structural evaluations.