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Radioactive N-ethyl [2, 3-14C]maleimide-S-glutathione (14C-NEM-S-G) was used as a model compound of glutathione conjugate. The metabolism of the conjugate in the extrarenal tissues was investigated in nephrectomized rats and perfused rat livers. When 14C-NEM-S-G was injected intravenously into nephrectomized rats, a significant amount of 14C-NEM-S-cysteine (14C-NEM-S-Cys) was detected in the blood, demonstrating that the conjugate could be metabolized to its cysteine form by extrarenal gamma-glutamyl transferase and dehydropeptidase-I. In the isolated liver perfusion with Krebs-Henseleit buffer containing 25 mM Hepes, both 14C-NEM-S-Cys and 14C-NEM-S-cysteinylglycine (14C-NEM-S-Cys-Gly) were formed from 14C-NEM-S-G. Furthermore, 14C-NEM-S-Cys-Gly was converted to 14C-NEM-S-Cys in the plasma, although 14C-NEM-S-G was not metabolized by the plasma itself. These results demonstrate that the liver and plasma contribute to the metabolism of glutathione conjugates in vivo.

Extrarenal metabolism of N-ethyl (2,3-14C) maleimide-S-glutathione, a model compound of glutathione conjugate.