SEQUENTIAL OXIDATION OF ALCOHOLS BY ALCOHOL DEHYDROGENASE

酒精脱氢酶(ADHS)对于 酶学的发展和广泛的应用。肝 ADHS一直是调查的主要焦点，并显示出广泛的 底物专一性，将醇从甲醇氧化为类固醇。 它们还具有将醛氧化为酸的能力。这 活动并没有得到广泛的认可，尽管有零星的 相关文献报道中的相关现象。主流观点认为， 然而，所报道的两种醛的动力学数值 氧化和乙醛歧化排除了生理性的 这一反应的相关性。马肝醇脱氢酶 (HL-ADH)不仅能够氧化醛，而且耐人寻味， 虽然是非生理性的副作用；但当在 在不影响这一活动的条件下，它完全有能力 催化剂催化脂肪醛氧化制酸 其效率可与其催化作用相提并论，甚至远远超过 酒精氧化。我们的重点是详细的动力学研究 确定反应的动力学数值，目标是 将实验结果与总体动力学方案相匹配。这 由于意想不到的额外动力，进球一直难以捉摸 我们发现的复杂性源于处理这两个问题的必要性 醛、游离醛和水合吉二醇的形式 不同的化合物。我们还在进一步开发方法，以 允许监控酒精脱氢酶的全系列反应 才能进行。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潜力，以评估 ADH同工酶的序列异质性及其对 结构、功能和生理效应。的资源 计算机图形学实验室是开展 结构评估。

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.