Catalase mediated conversion of cyanamide to an inhibitor of aldehyde dehydrogenase.
A minor pathway for cyanamide metabolism catalyzed by catalase is responsible for the conversion of cyanamide to an inhibitor of aldehyde dehydrogenase. Catalase itself is also inhibited by cyanamide. Both the activation of cyanamide by catalase and the inhibition of catalase by cyanamide were blocked in vivo by ethanol pretreatment, suggesting that these two processes are closely linked. Like other catalase oxidation reactions, the catalase mediated activation of cyanamide was inhibited by 3-amino-1,2,4-triazole in vivo and sodium azide in vitro. The relative formation of the active cyanamide metabolite was assessed in vitro by following the loss of yeast aldehyde dehydrogenase activity with time. Inhibition of the yeast enzyme by activated cyanamide was dependent on NAD+ or NADP+, a requirement not fulfilled by NADH or NADPH. Although H2O2 inhibited yeast aldehyde dehydrogenase in vitro and cyanamide inhibited hepatic catalase in vivo, the possible in hepatic H2O2 concentration following cyanamide administration does not account for the effects of cyanamide on ethanol metabolism. While the cyanamide activating enzyme has been identified as catalase, the reaction products of this reaction and, in particular, the structure of the active metabolite involved in the inhibition of aldehyde dehydrogenase remain unknown.
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001711:Biotransformation; D002374:Catalase / Q000502:physiology*; D002417:Cattle; D003484:Cyanamide / Q000378:metabolism* / Q000494:pharmacology; D003486:Cyanides / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001386:Azides; D003486:Cyanides; D003484:Cyanamide; D006861:Hydrogen Peroxide; D002374:Catalase; D000444:Aldehyde Dehydrogenase; D000640:Amitrole