ACETALDEHYDE DETOXIFICATION MECHANISMS IN DROSOPHILA-MELANOGASTER ADULTS INVOLVING ALDEHYDE DEHYDROGENASE (ALDH) AND ALCOHOL-DEHYDROGENASE (ADH) ENZYMES

The mechanism of acetaldehyde detoxification in Drosophila melanogaster adults has been studied by comparing physiological in vitro and in vivo data. ADH+ and ADH- flies, both lacking aldehyde dehydrogenase activity from ADH (ALDH(ADH)), ALDH (ALDH) or both enzymes were exposed to acetaldehyde or ethanol, and the toxicity and internal accumulation of both compounds were determined. Acetaldehyde was extremely lethal for flies whose ALDH activity had been inhibited by cyanamide, though acetaldehyde was effectively detoxified by flies whose ALDH(ADH) activity had been inhibited by acetone. After exposure to acetaldehyde, both acetaldehyde and ethanol rapidly accumulated in flies lacking ALDH activity, but not in flies lacking ALDH(ADH) activity. However, ethanol but not acetaldehyde quickly accumulated in flies lacking ALDH activity after exposure to ethanol. Our results provide in vivo evidence that, as opposed to larvae, in D. melanogaster adults acetaldehyde is mainly oxidized into acetate by means of ALDH enzymes. However, the reducing activity of the ADH enzyme, which transforms acetaldehyde into ethanol, also plays an essential role in the detoxification of acetaldehyde. Differences in ALDH activity might be important to explain the differences in ethanol tolerance found in natural populations.