Erythrocyte glutathione synthetase in 5-oxoprolinuria: kinetic studies of the mutant enzyme and detection of heterozygotes.
The primary metabolic defect in 5-oxoprolinuria is a generalized deficiency of glutathione synthetase. The activity of this enzyme was determined in cell-free extracts of erythrocytes from patients with 5-oxoprolinuria, their parents and a sibling as well as from normal control individuals. The following activities (pkat/mg of hemoglobin) for glutathione synthetase were obtained: homozygotes mean 0.10 (range 0.07-0.12), heterozygotes mean 3.1 (range 2.8-3.7) and control individuals mean 6.1 (range 5.4-6.7). These results indicate that 5-oxoprolinuria, i.e. the defective gluthione synthetase gene(s), is transmitted by autosomal recessive inheritance. Studies of the kinetics of the low remaining activity of erythrocyte glutathione synthetase in patients with 5-oxoprolinuria failed to reveal defective affinity for glycine, gamma-glutamyl-alpha-aminobutyrate, ATP and Mg2+ ions. Furthermore, the pH optimum, time curves and temperature dependence for the mutant enzyme activity did not significantly differ from the corresponding parameters observed with normal enzyme.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D000743:Anemia, Hemolytic / Q000201:enzymology / Q000235:genetics; D002675:Child, Preschool; D004151:Dipeptides / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005808:Genes, Recessive; D005981:Glutathione Synthase / Q000097:blood / Q000172:deficiency*; D005998:Glycine / Q000494:pharmacology; D006579:Heterozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007231:Infant, Newborn; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010453:Peptide Synthases / Q000172:deficiency*
D004151:Dipeptides; D000255:Adenosine Triphosphate; D010453:Peptide Synthases; D005981:Glutathione Synthase; D008274:Magnesium; D005998:Glycine