Nature of a Soluble, Glutathione-Dependent Enzyme System Active in Cleavage of Methyl Parathion to Desmethyl Parathion

Abstract

The nature of the enzyme, in the supernatant fraction of tissue homogenates of rat liver and insect mid-gut, that cleaves O, O-dimethyl O-p-nitrophenyl phosphorothioate (methyl parathion) to O-methyl O-p-nitrophenyl phosphorothioate (desmethyl parathion) was examined. The enzyme, from both sources, is inactivated by dialysis or gel filtration and its activity is effectively restored by addition of reduced glutathione (GSH). Many rat tissues are active in methyl parathion-demethylation, but highest activity occurs in the liver. Although the addition of GSH increases the activity of insect mid-gut and fat body, these insect enzymes fall short of the degrading activity of rat liver. The degradation product of methyl parathion as formed by the supernatant fraction of rat liver fortified with GSH was identified as the desmethyl derivation. Two metabolites, the desmethyl derivative and phosphoric acid, were detected from the insect mid-gut preparations when fortified with GSH. Rat liver has approximately 5.5 times as much GSH as the mid-gut of larvae of horn beetle, Xylitrupes dichotomus (L.). Cellulose chromatographic separation of the supernatant of rat liver and insect mid-gut homogenates reveals that the nature of these 2 enzyme proteins is different. The metabolic difference in the degradation of organophorphorus insecticides containing the P-O-methyl between mammals and insects is discussed in relation to the selective toxicity of these compounds.