EXTRARENAL METABOLISM OF N-ETHYL [2,3-^<14>C] MALEIMIDE-S-GLUTATHIONE, A MODEL COMPOUND OF GLUTATHIONE CONJUGATE

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Radioactive N-ethyl [2,3-^<14>C] maleimide-S-glutathione (^<14>C-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 ^<14>C-NEM-S-G was injected intravenously into nephrectomized rats, a significant amount of ^<14>C-NEM-S-cysteine (^<14>C-NEM-S-Cys) was detected in the blood, demonstrating that the conjugate could be metabolized to its cysteine form by extrarenal γ-glutamyl transferase and dehydropeptidase-I. In the isolated liver perfusion with Krebs-Henseleit buffer containing 25 mM Hepes, both ^<14>C-NEM-S-Cys and ^<14>C-NEM-S-cysteinylglycine (^<14>C-NEM-S-Cys-Gly) were formed from ^<14>C-NEM-S-G. Furthermore, ^<14>C-NEM-S-Cys-Gly was converted to ^<14>C-NEM-S-Cys in the plasma, although ^<14>C-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.
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