Studies on the displacement of methylthio groups by glutathione

Abstract

1. ¹⁴C-Methylthio-labelled 2-methylthio-4-ethylamino-6-tert-butylamino-sym-triazine (terbutryn), pentachlorothioanisole (PCTA), and 1,4-bis(methylthio)tetrachloro-benzene (bis-MTTCB) and their methylthio-oxidation congeners were reacted with glutathione (GSH) in the presence and absence of immobilized liver microsomal enzymes.

2. ¹³C-Methylthio-labelled terbutryn sulphoxide and terbutryn sulphone were used to study displacement of the methylthio moiety by GSH using ¹³C-n.m.r.

3. Methanesulphinic acid was identified as the group displaced by GSH from the methyl sulphones in vitro.

4. Methanesulphenic acid is proposed to be the group displaced by GSH from methyl sulphoxides forming methyl mercaptan, methyl glutathionyl disulphide and methane-sulphinic acid in vitro.

5. Rats given ¹⁴C-methylthio-labelled terbutryn, PCTA, bis-MTTCB, and their methylthio-oxidation congeners excreted ¹⁴CO₂ and ¹⁴C-methanesulphinic acid in varying amounts. These results were compared to the in vitro data.