In-vitro metabolism of O,O-diethyl S-(N-methylcarbamoylmethyl) phosphorodithioate by mouse liver

The in-vitro metabolism of O,O-diethyl S-(N-methylcarbamoymethyl) phosphorodithioate in mouse liver was studied. The major route of metabolism was via the mixed-function oxidases present in the microsomal fraction, which formed the oxygen analogue, O,O-diethyl hydrogen phosphorothioate and diethyl hydrogen phosphate upon addition of nicotinamide-adenine dinucleotide phosphate (NADPH). In the absence of NADPH, the carboxylic acid analogue (S-carboxymethyl O,O-diethyl phosphorodithioate) was isolated only from the microsomal fraction. Addition of glutathione to the 100 000 g supernatant resulted in no metabolism of the parent compound. However, addition of glutathione to the 10 000 g supernatant resulted in the carboxylic acid formed by amidase activity being further metabolised to O,O-diethyl hydrogen phosphorodithioate by a glutathione-dependent reaction.