Defective GSS does not synthesize GSH

Stable Identifier
R-HSA-5602901
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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In the second step in glutathione formation, gamma-glutamylcysteine (gGluCys) ligates with glycine (Gly) to form glutathione (GSH), catalysed by glutathione synthetase (GSS), a homodimeric enzyme present in the cytosol. Defects in GSS can cause glutathione synthetase deficiency (GSSD aka 5-oxoprolinase deficiency, MIM:266130), a severe, autosomal recessive disorder characterised by an increased rate of haemolysis, 5-oxoprolinuria and defective function of the central nervous system. In this condition, decreased levels of cellular glutathione result in overstimulation of gamma-glutamylcysteine synthesis and its subsequent conversion to 5-oxoproline. Mutations causing severe GSSD include R164Q, R267W, R283C, R125C and P314L (Shi et al. 1996).

Literature References
PubMed ID Title Journal Year
8896573 Mutations in the glutathione synthetase gene cause 5-oxoprolinuria

Shi, ZZ, Habib, GM, Rhead, WJ, Gahl, WA, He, X, Sazer, S, Lieberman, MW

Nat. Genet. 1996
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
glutathione synthase activity of GSS mutants:GSS mutants:Mg2+:Mg2+ [cytosol]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
inherited metabolic disorder 655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
Authored
Reviewed
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