Extrarenal metabolism of N-ethyl [2, 3-14C] maleimide-S-glutathione, a model compound of glutathione conjugate.
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.
Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
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Hirota
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Komai
D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000493:pharmacokinetics*; D009392:Nephrectomy; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D008301:Maleimides; C054449:N-ethylmaleimide-S-glutathione; D005978:Glutathione