title: Decrease of intracellular cystine content in cystinotic fibroblasts by inhibitors of gamma-glutamyl transpeptidase.
abstract: Cystine content of skin fibroblasts derived from patients with cystinosis was decreased by inhibitors of gamma-glutamyl transpeptidase, the initial enzyme in glutathione catabolism. The addition of maleate or the gamma-glutamyl hydrazone of alpha-ketobutyric acid to culture medium (1-20 mM) resulted in dose-dependent decreases of up to 55% on intracellular cystine content of cystinotic cells in 24 h. L-Serine in sodium borate buffer (40 mM each) produced similar results and further decreased cystine levels to 14% of cystinotic control values after 10 days incubation. Analysis of intracellular amino acids showed that, in general, other amino acids remained unchanged following serine-borate treatment. These results suggest that cystine storage in cystinotic tissues may be related to metabolism of glutathione.
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D002478:Cells, Cultured; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008298:Maleates / Q000494:pharmacology; D012694:Serine / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors*
chemical_list: D000596:Amino Acids; D005971:Glutamates; D008298:Maleates; D012694:Serine; D003553:Cystine; C029393:alpha-ketobutyric acid gamma-glutamyl hydrazone; D005723:gamma-Glutamyltransferase