OXYGEN-18 STUDIES ON THE CHEMICAL MECHANISMS OF THE MIXED FUNCTION OXIDASE CATALYZED DESULFURATION AND DEARYLATION REACTIONS OF PARATHION

¹ Division of Toxicology, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee

Parathion was incubated with rabbit-liver microsomes and a reduced nicotinamide adenine dinucleotide phosphate-generating system in an atmosphere of ¹⁸O₂ or in a medium containing H₂¹⁸O. The products of the reactions were isolated and the ¹⁸O enrichment was determined by gas chromatography-mass spectrometry. The data clearly show that oxygen from ¹⁸O₂ is retained in paraoxon, the product of the desulfuration reaction, and in diethylphosphate, the hydrolysis product of paraoxon, but not in diethylphosphorothionate, the product of the dearylation reaction. When the reaction is carried out in H₂¹⁸O, the label is found in diethylphosphorothionate but not paraoxon. With the results of these experiments, we have postulated a chemical mechanism for the mixed function oxidase-catalyzed metabolism of parathion to paraoxon and diethylphosphorothionate.