Figure 5: Proposed model which can provide a feasible explanation for the evolution of enzymes which methylate AsIII in hepatocytes: As(OH)3 is enzymatically converted (*) to the trivalent As compounds MeAs(OH)2 and Me2AsOH, which readily react with cytosolic glutathione (GSH) to MeAs(GS)2 and Me2AsGS. The increased stability of As-S bonds in MeAs(GS)2 and Me2AsGS compared to the much less stable (GS)3As will facilitate the efflux of the former species to the bloodstream by MRP export pumps [136]. The translocation of these species to the kidneys and subsequent oxidation will result in the excretion of methylated AsV species in urine [142].