Glutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria).
Enzyme studies on placenta, cultured skin fibroblasts, and erythrocytes from two sisters with the inborn error 5-oxoprolinuria (pyroglutamic aciduria) indicate that the metabolic lesion in this disease is at the glutathione synthetase (EC 6.3.2.3) step of the gamma-glutamyl cycle. Excessive urinary excretion of 5-oxoproline by these patients appears to be associated with increased synthesis of gamma-glutamyl-cysteine and formation of 5-oxoproline from this dipeptide. Thus, 5-oxoproline is produced in amounts that exceed the normal capacity of 5-oxoprolinase to convert it to glutamate. The data indicate that it may be possible to identify individuals who are heterozygous for this trait by determinations of erythrocyte glutathione synthetase.
D000217:Acyltransferases / Q000378:metabolism; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology* / Q000652:urine; D000596:Amino Acids / Q000652:urine*; D002675:Child, Preschool; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010453:Peptide Synthases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology; D011392:Proline / Q000378:metabolism; D011760:Pyrrolidinones / Q000652:urine*; D011761:Pyrrolidonecarboxylic Acid; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000596:Amino Acids; D011760:Pyrrolidinones; D011392:Proline; D000217:Acyltransferases; D005723:gamma-Glutamyltransferase; D010453:Peptide Synthases; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid