Effects of aldehyde dehydrogenase inhibitors on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain.
The effects of the aldehyde dehydrogenase inhibitors disulfiram, coprine and cyanamide on enzymes involved in the metabolism of biogenic aldehydes in rat liver and brain were studied. Both liver and brain aldehyde dehydrogenase activities were significantly decreased in rats pretreated with these drugs. In the liver, the low-Km aldehyde dehydrogenase activity was markedly decreased by all three drugs after 2 and 24 hr whereas only cyanamide inhibited the high-Km enzymes. The brain ALDH-activity with a low acetaldehyde concentration was significantly decreased by coprine and cyanamide at both times tested, whereas disulfiram caused no change after 2 hr but an inhibition of 38% after 24 hr. The brain ALDH-activity with a high acetaldehyde concentration was significantly decreased by coprine and cyanamide but not by disulfiram. The activity of the substrate specific enzyme succinate semialdehyde dehydrogenase in brain was slightly but significantly decreased in rats pretreated with cyanamide but not in rats pretreated with disulfiram or coprine. None of the drugs caused any changes in the activities of aldehyde reductase and monoamine oxidase in brains in vivo. The activity of monoamine oxidase in liver was significantly decreased by coprine after 24 hr. In contrast to the effects obtained in vivo, disulfiram was found to be an inhibitor in vitro of brain succinate semialdehyde dehydrogenase and liver monoamine oxidase. Aldehyde reductase was slightly inhibited by both disulfiram and 1-aminocyclopropanol in vitro.
D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003484:Cyanamide / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D000447:Aldehydes; D005973:Glutamine; C014423:coprine; D000431:Ethanol; D003484:Cyanamide; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram