SEQUENTIAL OXIDATION OF ALCOHOLS BY ALCOHOL DEHYDROGENASE

酒精脱氢酶，ADHS，一直是 酶学的发展和广泛的应用。肝脏ADHS 一直是调查的主要焦点，并显示出广泛的基础 特异地，将酒精从甲醇氧化为类固醇。他们也 有能力将醛氧化成酸。此活动不是 得到广泛认可，尽管有零星的报告在 相关现象的文献。然而，流行的观点是 已报道的醛氧化和乙醛氧化的动力学数值 乙醛错位排除了这一点的生理相关性 反应。这项提议的核心是马肝酒精 脱氢酶，HL-ADH，不仅能够氧化醛作为一种 耐人寻味的，尽管是非生理性的副作用；但当检测到 在不影响这一活动的条件下，它完全是 能够催化脂肪醛氧化成酸 其催化效率可与甚至远高于 它对酒精氧化的催化作用。在过去的一年里，我们的重点是 一直在进行详细的动力学研究以确定动力学 反应的数值，并将它们与整体动力学方案相匹配。 我们还在开发方法，以便能够确定 其他乙醇脱氢酶的易导性 醛被氧化成酸。我们目前的重点一直是 动力学研究。随着我们获得更多关于人类能力的信息 其他酒精脱氢酶要氧化醛，我们将需要 开始比较它们的结构，也开始与没有 容易氧化醛。到那时，我们预计将作出重大努力 重点介绍了如何利用计算机图形学实验室进行解读 序列的结构/活性关系及其解释 相关蛋白质的分析。目前我们还在数据中 正在收集阶段，但我们正在启动一个与P.Babbitt博士合作的项目 结构对齐和图形将成为 项目。

The alcohol dehydrogenases, ADHs, have been pivotal to the developent 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. The core of this proposal is that 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 in the past year has been on conducting detailed kinetic studies to determine the kinetic values for the reaction and fitting them to an overall kinetic scheme. We are also developing the methodology to allow determining the ability of other alcohol dehydrogenases to conduct the facile oxidation of aldehydes to acids. Our current focus has been on kinetic studies. As we obtain more information on the ability of other alcohol dehydrogenases to oxidize aldehydes, we will need to begin to compare their structures and also with ADHs that do not readily oxidize aldehydes. At that time we anticipate a major effort focused on the use of the Computer Graphics Laboratory to interpret the structure/activity relations and interpretation of sequence analyses of related proteins. At present we are still in the data gathering stage but we are starting a project with Dr. P. Babbitt on structural alignments and graphics will become an essentia part of the project.