Metabolism of acrylonitrile to cyanide. In vitro studies.
In liver fractions from Sprague-Dawley rats, the metabolism of acrylonitrile (VCN) to cyanide (CN-) was localized the microsomal fraction and required NADPH and O2 for maximal activity. The biotransformation of VCN to CN- was characterized with respect to time, microsomal protein concentration, pH, and temperature. Metabolism of VCN was increased in microsomes obtained from phenobarbital-, Aroclor 1254-, or 3-methylcholanthrene-treated rats (479%, 414%, and 142% of control, respectively) and decreased with CoCl2 treatment (54% of control). The KM estimated for VCN with the phenobarbital (54.8 +/- 9.5 mM) or Aroclor 1254 (40.9 +/- 4.1 mM) preparation was lower than the control (190.7 +/- 19.7 mM). Addition of SKF 525-A or CO to incubation mixtures inhibited VCN metabolism. Addition of the epoxide hydratase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from VCN. Addition of glutathione, cysteine, D-penicillamine, or 2-mercaptoethanol enhanced the release of CN- from VCN. These findings indicate that VCN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.
D000181:Acrylonitrile / Q000378:metabolism*; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D003486:Cyanides / Q000378:metabolism*; D003543:Cysteamine / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D014239:Trichloroepoxypropane / Q000494:pharmacology
D001140:Aroclors; D003486:Cyanides; D009570:Nitriles; D009243:NAD; D020111:Chlorodiphenyl (54% Chlorine); D014239:Trichloroepoxypropane; D009249:NADP; D003543:Cysteamine; D003577:Cytochrome P-450 Enzyme System; D003576:Electron Transport Complex IV; D000181:Acrylonitrile; D010634:Phenobarbital