A comparative study on the effects of disulfiram, cyanamide and 1-aminocyclopropanol on the acetaldehyde metabolism in rats.
1-aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH) in vivo and in vitro. Like cyanamide it has a rapid onset of action in vivo with the highest inhibition occurring after 2--24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low-Km ALDH strongly in vivo, however, in markedly different doses. Cyanamide inhibited the high-Km ALDH only in vivo, whereas in vitro, the hihgh-Km ALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low-Km enzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram-ethanol reaction are discussed.
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000097:blood / Q000378:metabolism; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D000431:Ethanol / Q000097:blood / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D051381:Rats
D003486:Cyanides; D003521:Cyclopropanes; D000431:Ethanol; D003484:Cyanamide; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde; D004221:Disulfiram