Metabolism of allylnitrile to cyanide: in vitro studies.
In liver fractions from male Sprague-Dawley rats, the metabolism of allylnitrile (ALN) to cyanide (CN-) was localized in the microsomal fraction and required NADPH and oxygen for maximal activity. The biotransformation of ALN to CN- was characterized with respect to time, microsomal protein concentration, pH and temperature. Metabolism of ALN was increased in microsomes obtained from phenobarbital-treated rats (160% of control) and decreased with cobaltous chloride and beta-diethyl aminoethyl-2,2-diphenyl pentanoate (SKF 525-A) treatments (48% of control). Addition of SKF 525-A to the incubation mixtures inhibited ALN metabolism to CN-. Addition of the epoxide hydrolase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN- from ALN. Addition of glutathione, cysteine, D-penicillamine, and 2-mercaptoethanol enhanced the release of CN- from ALN. These findings indicate that ALN is metabolized to CN- via a cytochrome P-450-dependent mixed-function oxidase system.
Farooqui
M Y
MY
Department of Biology, University of Texas, Pan American Edinburg 78539.
Ybarra
B
B
Piper
J
J
D000818:Animals; D001711:Biotransformation; D003486:Cyanides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D009570:Nitriles / Q000378:metabolism* / Q000493:pharmacokinetics; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D003486:Cyanides; D009570:Nitriles; D013438:Sulfhydryl Compounds; D015636:Magnesium Chloride; C031103:crotononitrile; C015660:allyl cyanide; D009249:NADP; D010634:Phenobarbital