Formation of gamma-glutamycyst(e)ine in vivo is catalyzed by gamma-glutamyl transpeptidase.
These studies indicate that gamma-glutamylcyst(e)ine, found in the urine of a patient with gamma-glutamyl transpeptidase deficiency and also in the urine of experimental animals injected with glutathione or with inhibitors of gamma-glutamyl transpeptidase, is formed by the action of gamma-glutamyltranspeptidase. The evidence demonstrates that transpeptidation between glutathione and cystine occurs in vivo and also that this reaction constitutes a significant physiological function of the enzyme. The appearance of large amounts of gamma-glutamylcyst(e)ine in the urine seems to reflect an inhibitory effect of glutathione on the transport of gamma-glutamylcyst(e)ine into cells. The findings also indicate that conversion of glutathione to gamma-glutamylcysteine by hydrolytic cleavage of the COOH-terminal glycine moiety of glutathione (or analogous cleavage of glutathione disulfide) is not a quantitatively significant pathway. The results reported here show that gamma-glutamyl transpeptidase activity is not completely absent in a patient found to have a deficiency of this enzyme and that the activity of the enzyme is not abolished in experimental animals treated with potent gamma-glutamyl transpeptidase inhibitors.
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000652:urine; D004151:Dipeptides / Q000096:biosynthesis* / Q000652:urine; D005971:Glutamates / Q000096:biosynthesis / Q000652:urine; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007668:Kidney / Q000378:metabolism; D051379:Mice; D010179:Pancreas / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000172:deficiency / Q000378:metabolism*
D004151:Dipeptides; D005971:Glutamates; D007202:Indicators and Reagents; D011725:Pyridines; C030954:gamma-glutamylcystine; C030953:2-vinylpyridine; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C029351:4-vinylpyridine; D003545:Cysteine; C017341:gamma-glutamylcysteine