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Metabolism of methacrylonitrile to cyanide: In vitro studies

✍ Scribed by Farooqui, Mohammed Y. H. ;Diaz, Rolando G. ;Cavazos, Rogelio

Book ID: 102875594
Publisher: John Wiley and Sons
Year: 1990
Tongue: English
Weight: 557 KB
Volume: 5
Category: Article
ISSN: 0887-2082
DOI: 10.1002/jbt.2570050205

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✦ Synopsis

In liver fractions from male Sprague-Dawley rats, the metabolism of methacrylonitrile (MeAN) to cyanide (CN-) was localized in microso-ma1 fraction and required reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen for maximal activity. The biotransformation of MeAN to CN-was characterized with respect to time, microsomal protein concentration, pH, and temperature. Metabolism of MeAN was increased in microsomes obtained from phenobarbital-treated rats (310% of control) and decreased with CoCI, and SKF 525 A treatments (55% and 61%, respectively). Addition of the epoxide hydratase inhibitor, 1,1,1-trichloropropane 2,3-oxide, decreased the formation of CN - from MeAN. Addition of glutathione, cysteine, Dpenicillamine, and 2-mercaptoethanol enhanced the released of CN-from MeAN. These findings indicate that MeAN is metabolized to CN-via a cytochrome P-450-dependent mixed-function oxidase system.

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