IDENTIFICATION AND METABOLISM OF SELENOCYSTEINE-GLUTATHIONE SELENENYLSULFIDE (CYSESG) IN SMALL-INTESTINE OF MICE ORALLY EXPOSED TO SELENOCYSTINE

This investigation was carried out to elucidate the chemical form of s elenium-containing metabolite in small intestine of ICR male mice oral ly administered selenocystine (CySeSeCy). The metabolite in intestinal cytosol of mice treated with CySeSeCy (50 mg/kg) was identified as se lenocysteine-glutathione selenenyl sulfide (CySeSG) by high performanc e liquid chromatography using a gel filtration and reversed phase colu mn. Hydrogen selenide formation was caused as a result of the anaerobi c reaction between the CySeSG and liver cytosol containing selenocyste ine beta-lyase, which specifically acts on selenocysteine (CySeH). Eff ects of GSH or glutathione reductase on hydrogen selenide formation fr om CySeSG reacted with the liver cytosol were examined. The CySeSG was nonenzymatically reduced to CySeH by excess GSH in the liver cytosol. It was also recognized that CySeSG was enzymatically reduced to CySeH by glutathione reductase in the presence of NADPH. These results indi cate that the chemical form of this metabolite is CySeSG, which has a molecular weight of 473, the CySeSG is then reduced by excess GSH and/ or glutathione reductase yielding CySeH, which is decomposed by seleno cysteine beta-lyase to hydrogen selenide. CySeSG may be a stable precu rsor of hydrogen selenide in animals.