On the mechanism of 5-oxoproline overproduction in 5-oxoprolinuria
| Autor: | A. Larsson, Barbro Mattsson |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Erythrocytes
Proline Clinical Biochemistry Glycine Biology Biochemistry chemistry.chemical_compound Biosynthesis Humans Peptide Synthases Overproduction Amino Acid Metabolism Inborn Errors Biochemistry (medical) Glutamate receptor General Medicine Glutathione Control subjects Pyrrolidinones Glutathione synthetase Pyrrolidonecarboxylic Acid Kinetics chemistry 5-OXOPROLINURIA Cysteine |
| Zdroj: | Clinica Chimica Acta. 67:245-253 |
| ISSN: | 0009-8981 |
| DOI: | 10.1016/0009-8981(76)90332-6 |
| Popis: | The primary metabolic defect in 5-oxoprolinuria (pyroglutamic aciduria) is the lack of glutathione synthetase. The mechanism of the concomitant overproduction of 5-oxoproline was studied using cell-free extracts of erythrocytes from control individuals and from patients with 5-oxoprolinuria. Such extracts catalyzed the synthesis of 5-oxoproline from L-glutamate. Addition of ATP, Mg ions and alpha-aminobutyrate was needed for optimal activity. The conversion of glutamate to 5-oxoproline occurred in two steps, catalyzed by gamma-glutamyl-cysteine synthetase and gamma-glutamyl cyclotransferase, respectively. Extracts of erythrocytes from control subjects and patients with 5-oxoprolinuria had identical capacity to synthesize 5-oxoproline. The conversion of glutamate to 5-oxoproline was markedly inhibited by reduced glutathione, which exerted its effect on the gamma-glutamyl-cysteine synthetase step. The following mechanism is postulated for the overproduction of 5-oxoproline in 5-oxoprolinuria: the deficiency of glutathione synthetase causes a lack of glutathione which is an essential feed-back inhibitor in the initial step of its biosynthesis. Therefore gamma-glutamyl-cysteine is produced in excessive amounts and it is subsequently converted to 5-oxoproline (and cysteine) by gamma-glutamyl cyclotransferase. This overproduction of 5-oxoproline exceeds the capacity of the 5-oxoprolinase and 5-oxoproline accumulates in body fluids. |
| Databáze: | OpenAIRE |
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