Metabolism of phosphorus-containing compounds by pig liver microsomal FAD-containing monooxygenase

Abstract

Oxidative desulfuration of phosphonate insecticides such as fonofos ( S-phenyl ethyl ethylphosphonodithioate) and its analogs is catalyzed by pig liver microsomal FAD-containing monooxygenase, although desulfuration of phosphorodithioates, such as parathion, is not. Substitution of an alkyl group for the remaining alkoxy group, as in S-phenyl diethylphosphinodithioate, did not increase its oxidation rate. Diethylphenylphosphine sulfide, containing 3 phosphorus-carbon bonds, was actually a poorer substrate than fonofos. Replacement of the S-phenyl group of fonofos with an O-phenyl group increased the K m value above the solubility limit. Trivalent phosphorus-containing compounds were also excellent substrates for this enzyme. Diethylphenylphosphine had a K m value lower than 2.5 μM. Diethyl phenylphosphonite also appeared to be an excellent substrate but its rapid nonenzymatic hydrolysis and/or oxidation precluded accurate K m determinations. Stoichiometry studies with diethylphenylphosphine and its sulfide showed that O 2 and NADPH consumption were approximately equal to the substrate consumed. The major metabolite of both diethylphenylphosphine and its sulfide was the phosphine oxide. These results show that microsomal FAD-containing monoxygenase of pig liver has activity as a phosphorus-oxidase, in addition to its well characterized nitrogen- and sulfur-oxidase roles.