The metabolic activation of cyanamide to an inhibitor of aldehyde dehydrogenase is catalyzed by catalase.
The inhibition of aldehyde dehydrogenase by cyanamide is dependent on an enzyme catalyzed conversion of the latter to an active metabolite. The following results suggest that catalase is the enzyme responsible for this bioactivation. The elevation of blood acetaldehyde elicited by cyanamide after ethanol administration to rats was attenuated more than 90 percent by pretreatment with the catalase inhibitor, 3-amino-1,2,4-triazole. This attenuation was dose dependent and was accompanied by a reduction in total hepatic catalase activity. Although hepatic catalase was also inhibited by cyanamide, a positive correlation between blood acetaldehyde and hepatic catalase activity was observed. In vitro, the activation inhibitor, 3-amino-1,2,4-triazole. This attenuation was dose dependent and was accompanied by a reduction in total hepatic catalase activity. Although hepatic catalase was also inhibited by cyanamide, a positive correlation between blood acetaldehyde and hepatic catalase activity was observed. In vitro, the activation of cyanamide was catalyzed by a) the rat liver mitochondrial subcellular fraction, b) the 50-65% ammonium sulfate mitochondrial fraction and c) purified bovine liver catalase. Cyanamide activation was inhibited by sodium azide. Since much of the hepatic catalase is localized in the peroxisomes and since peroxisomes and mitochondria cosediment, the cyanamide activating enzyme, catalase, is likely of peroxisomal and mitochondrial origin.
D000079:Acetaldehyde / Q000097:blood; D000444:Aldehyde Dehydrogenase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002384:Catalysis; D002417:Cattle; D003484:Cyanamide / Q000378:metabolism* / Q000494:pharmacology; D003486:Cyanides / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D003486:Cyanides; D003484:Cyanamide; D002374:Catalase; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D000640:Amitrole