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
Participates
Catalyst Activity

glutathione synthase activity of GSS mutants:GSS mutants:Mg2+:Mg2+ [cytosol]

Normal reaction
Functional status

Loss of function of GSS mutants:GSS mutants:Mg2+:Mg2+ [cytosol]

Status
Disease
Name Identifier Synonyms
inherited metabolic disorder DOID:655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
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