Inhibition of aldehyde dehydrogenase

Abstract

The first two steps in the metabolism of ethanol to acetate via acetaldehyde are predominantly catalyzed by alcohol dehydrogenase and aldehyde dehydrogenase (ALDH), respectively. The efficiency of the enzymes involved in acetaldehyde disposition in humans is such that, during ethanol metabolism, blood acetaldehyde levels normally remain in the 1–2 µM range (section 10.4). Higher blood acetaldehyde levels are observed, however, during the disulfiram-ethanol reaction (DER), a condition induced by the ingestion of ethanol in individuals pretreated with disulfiram (DSSD). This led early to the surmise that the administration of DSSD results in an inhibition of acetaldehyde metabolism, and that the resulting raised acetaldehyde levels are responsible for the phenomenology of the DER (section 10.5). Moreover, because the DER is so intensely unpleasant, DSSD has been adopted as an aversely protective agent in the treatment of alcoholism (Chapter 11). This, in turn, has focused intense research interest on the enzymes involved in acetaldehyde metabolism and the mechanism of their inhibition.