Mechanism of alcohol sensitivity and disulfiram-ethanol reaction.
Human aldehyde dehydrogenase (ALDH) consists of two main isozymes with low and high Km for aldehyde. ALDH isozymes in hair sheats were tested from 40 Japanese using isoelectric focusing and blood acetaldehyde determination with gas chromatography. About 43% of Japanese, who lacked the low Km enzyme (ALDH I) showed an elevated acetaldehyde concentration due to their inability to metabolize acetaldehyde quickly and effectively. Studies regarding the inhibitory reaction of disulfiram and its metabolites have been performed. Among the metabolites, diethylamine inhibited the low Km enzyme strongly. It is presumed that vasomotor symptoms and high acetaldehyde concentration in blood after alcohol intake in patients who are treated with disulfiram might be mainly due to a decrease in activity of the low Km enzyme caused by diethylamine which is produced in vivo as one of the metabolites from disulfiram, rather than to an inhibitory reaction of disulfiram only. Thus, alcohol sensitivity in Mongoloids and disulfiram-ethanol reaction may have a common mechanism.
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism; D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D044466:Asian People; D004048:Diethylamines / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006197:Hair / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*
D004048:Diethylamines; D007527:Isoenzymes; D000431:Ethanol; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram