Biotransformation of methyl parathion by human foetal liver glutathione S-transferases: an in vitro study.
The role of human foetal liver glutathione S-transferases in the detoxification of methyl parathion was investigated. Glutathione S-transferases were partially purified by affinity chromatography utilizing reduced glutathione as the ligand coupled to epoxy-activated Sepharose 4B. This resulted in the isolation of material with an average activity (mean +/- S.E.) of 58.90 +/- 4.83 mumol 1-chloro-2,4-dinitrobenzene conjugate formed/min per mg, representing a purification of 70-fold. These partially purified foetal liver transferases catalysed the metabolism of methyl parathion exclusively to desmethyl parathion via O-dealkylation. High-performance liquid chromatography, radiometric analysis of the enzymic reaction, and co-chromatography with reference standard on thin-layer chromatography confirmed the sole metabolite as desmethyl parathion. The range of foetal liver activity towards methyl parathion was from 30 to 122 nmol desmethyl parathion formed/min per mg. Analysis of the kinetic parameters of three partially purified foetal liver preparations with gestational ages of 14, 16 and 21 weeks resulted in Km values for methyl parathion of 0.24, 0.38 and 0.86 mM, respectively; whereas, the Km values assessed for glutathione were 0.20, 0.10 and 0.18 mM. The ability of human foetal liver glutathione S-transferases to catalyse the metabolism of methyl parathion exclusively to desmethyl parathion via O-dealkylation represents a major qualitative biochemical difference from the rat-liver isozymes.
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005865:Gestational Age; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008743:Methyl Parathion / Q000378:metabolism*; D010278:Parathion / Q000031:analogs & derivatives*
D008743:Methyl Parathion; D010278:Parathion; D005982:Glutathione Transferase