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Pathway Description
Glutathione Synthetase Deficiency
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2022-09-28
Glutathione Synthetase Deficiency (5-Oxoprolinuria; Pyroglutamic Aciduria; GSD) is a rare inborn error of metabolism (IEM) which arises from a disfunctional gene called GSS. This gene is responsible for glutathione synthetase. Glutathione synthetase is the second enzyme in the glutathione biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione. A defect in this enzyme results in accumulation of pyroglutamic acid and gamma-glutamylcysteine in urine and blood; decrease level of glutathione in erythrocytes; increase urinary excretion of 5-oxoproline.
GSD is typically distinguished by three levels of severity. Those levels naturally being mild, moderate and severe. Being with the former, mild GSD can lead to a harmful condition known as hemolytic anemia. This occurs when red blood cells are destroyed. Although not as common, it is also possible for patients affected with GSD to excrete in their urine elevated quantities of 5-oxoproline (hence the other name for this condition shown in the first sentence of this description). The accumulation of high levels of 5-oxoproline (and hence the elevated level of secretion of this compound) is a direct consequence of glutathione being improperly processed by the body. Turning now to the second level of severity, moderate, it is typical to see affected patients experience experience the two symptoms described above, in addition to metabolic acidosis. The latter condition being the consequence of high acidity levels in the blood as well as other tissues. Finally, individuals with severe GSD may suffer from a wide variety of neurological symptoms. This could include anything from ataxia and slowed reactions, to psychomotor retardation, mental retardation and seizures.
References
Glutathione Synthetase Deficiency References
[Uniprot: P48637](http://www.uniprot.org/uniprot/P48637)
[OMIM: Entry 266130](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=266130)
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Glutathione Metabolism References
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Pubmed: 16710414
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