Role of dehydropeptidase-I in the metabolism of glutathione and its conjugates in the rat kidney.
14C-N-Ethylmaleimide-S-cysteinylglycine was used to investigate the role of dehydropeptidase-I in the metabolism of glutathione conjugates. The dipeptide was rapidly hydrolyzed to 14C-N-ethylmaleimide-S-cysteine in isolated rat renal cells, and subsequently acetylated to 14C-N-ethylmaleimide-S-N-acetylcysteine. Cilastatin, a specific inhibitor of dehydropeptidase-I, strongly inhibited the hydrolysis of the dipeptide by the isolated cells. In rat kidney homogenates, the marked inhibitory effect of cilastatin was also observed on the hydrolysis of cystinyl-bis-glycine and leukotriene D4, which are dipeptide intermediates in the biotransformation of oxidized glutathione and endogenous glutathione conjugate, respectively. In contrast, the inhibitory effect of bestatin, a potent inhibitor of aminopeptidase-M, was much smaller than that of cilastatin on the hydrolysis of these dipeptides by the renal cells and homogenates. These results suggest that dehydropeptidase-I plays a more important role in the metabolism of glutathione and its conjugates than aminopeptidase-M does.
D000818:Animals; D002478:Cells, Cultured; D015377:Cilastatin; D003521:Cyclopropanes / Q000494:pharmacology; D004150:Dipeptidases / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D005033:Ethylmaleimide / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism
D003521:Cyclopropanes; D004151:Dipeptides; D013189:SRS-A; D015377:Cilastatin; C022291:cystinylglycine; D004150:Dipeptidases; C038937:dipeptidase; D005978:Glutathione; D007930:Leucine; C012211:ubenimex; D005033:Ethylmaleimide