PT  - JOURNAL ARTICLE
AU  - J. HES
AU  - L. A. STERNSON
TI  - THE METABOLISM OF ACETOPHENONE OXIME IN RAT LIVER HOMOGENATES
DP  - 1974 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 345--350
VI  - 2
IP  - 4
4099  - http://dmd.aspetjournals.org/content/2/4/345.short
4100  - http://dmd.aspetjournals.org/content/2/4/345.full
SO  - Drug Metab Dispos1974 Jul 01; 2
AB  - The metabolism of [7-14C]acetophenone oxime was studied in rat liver homogenates to help evaluate the stability of the oxime functional group. The oxime was stable to oxidative and hydrolytic transformations. However, under anaerobic conditions, acetophenone oxime is reduced with some degree of stereoselectivity by rat liver to yield the corresponding hydroxylamine, N-hydroxy-1-phenyl-1-aminoethane, [α]D20 = -7°. At least two enzyme systems catalyze oxime reduction in oxygen-free atmospheres. A microsomal oxime reductase is present which requires NADPH as cofactor, but functions independently of cytochrome P-450. A second oxime reductase occurs in cytosol and also utilizes NADPH as hydrogen donor. These oxime reductases are apparently low activity enzymes and constitute a relatively minor pathway in a quantitative sense. Further reduction of the hydroxylamine to the corresponding amine was not observed, and no other major metabolites could be detected. These results were consistent with electrochemical measurements (cyclic voltammetry) made in aqueous buffer solutions, which demonstrated that oximes are readily reduced (Ep/2 = -0.25 V), but that the hydroxylamine is relatively resistant to further reduction (Ep/2 = -0.60 V) at solid electrode surfaces. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics