Studies on the metabolism of diethyl 4-nitrophenyl phosphorothionate (parathion) in vitro

Abstract

The metabolism of the phosphorothionate parathion in vitro was examined by using [32P]parathion and microsomes isolated from the livers of various animal species. The major metabolic products of parathion in this system in vitro were identified as diethyl 4-nitrophenyl phosphate (paraoxon), diethyl hydrogen phosphate, diethyl hydrogen phosphorothionate and p-nitrophenol. The reaction leading to the formation of diethyl hydrogen phosphorothionate and p-nitrophenol requires the same cofactors (NADPH and oxygen) required for metabolism of parathion to its active anti-acetyl-cholinesterase paraoxon. The enzyme activity towards parathion per unit weight of liver is increased some 65-130 percent by pretreatment of male rats with phenobarbital and 3, 4-benzopyrene. The metabolism of parathion is inhibited by incubation in a nitrogen atmosphere and in an atmosphere containing carbon monoxide. Pure oxygen is also inhibitory. These results are discussed in terms of a deficiency of oxygen for maximal activity as well as the lability of some component of the system to oxidation.