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.
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