Glutathione synthetase deficient human fibroblasts in culture.
Cultured skin fibroblasts from patients with 5-oxoprolinuria caused by hereditary deficiency of glutathione synthetase have decreased levels of the corresponding enzyme as well as of glutathione. Fibroblasts from the same patients accumulated gamma-glutamyl cysteine, but the levels were lower than those of glutathione in control fibroblasts. The uptake of [35S]cystine was equally rapid in control and patient fibroblasts. In the acid-soluble fraction gamma-glutamyl-[35S]cysteine accumulated in fibroblasts from patients but not from controls. Appreciable turnover of gamma-glutamyl cysteine and glutathione in the respective cell strains was observed, the half-lives of these pools being approximately 5 hours. The growth rate of mutant fibroblasts in culture was significantly slower than that of control fibroblasts. There was no significant accumulation of 5-oxoproline in the culture medium.
D002455:Cell Division; D002478:Cells, Cultured; D003553:Cystine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism; D005981:Glutathione Synthase / Q000172:deficiency*; D006801:Humans; D007700:Kinetics; D010453:Peptide Synthases / Q000172:deficiency*
D004151:Dipeptides; D003553:Cystine; D010453:Peptide Synthases; D005981:Glutathione Synthase; D005978:Glutathione; C017341:gamma-glutamylcysteine