Metabolism of 2-methyl-2-(methylthio)-propionaldehyde 0-(methylcarbamoyl) oxime (Temik) in mammals and insects

Abstract

The metabolism of Temik in mammals and insects was studied using four separate radiolabeled preparations of the parent compound and two preparations of its sulfoxide derivative. These preparations were as follows: 2-methyl-2-(methylthio)propionaldehyde 0-(methylcarbamoyl-carbonyl-C¹⁴) oxime, 2-methyl-2-(methylthio-S³⁵)propionaldehyde 0-(methylcarbamoyl) oxime, 2-methyl-2-(methyl- C¹⁴-thio)propionaldehyde 0-(methylcarbamoyl) oxime, 2-methyl-2-(methylthio)propionaldehyde-2-C¹⁴ 0-(methylcarbamoyl) oxime, 2-methyl-2-(methylsulfinyl)propionaldehyde 0-(methylcarbamoy-carbonyl-C¹⁴) oxime, and 2-methyl-2-(methylsulfinyl-S³⁵)propionaldehyde 0-(methylcarbamoyl) oxime. Degradation of Temik, in vitro, by various subcellular fractions of rat liver was found to be inefficient unless these systems were fortified with reduced nicotin-amid-adenine dinucleotide phosphate. The greatest metabolism occurred after incubation of Temik with 15,000 G solubles fortified with NADPH₂ which resulted in degradation of 95% of the material. Five chloroform-extractable metabolites were formed by this enzyme system. These metabolites were isolated by thin layer chromatography and tentatively identified as: 2-methyl-2-(methylsulfinyl)propionaldehyde 0-(methylcarbamoyl) oxime, 2-methyl-2-(methylsulfonyl)propionaldehyde 0-(methylcarbamoyl) oxime, 2-methyl-2-(methylthio)propionaldoxime, 2-methyl-2-(methylsulfonyl)propionaldoxime. The major metabolite formed by the 15,000 G solubles of rat liver was the methyl-sulfinyl derivative of Temik which constituted approximately 50% of the total materials. Additional degradative product(s) of a water soluble nature were present. ...