Defective GSS does not synthesize GSH

Stable Identifier
R-HSA-5602901
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Defective GSS does not synthesize GSH
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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

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

Nat. Genet. 1996
Participants
Input
Participates
as an event of
Catalyst Activity

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

Physical Entity
GSS mutants:GSS mutants:Mg2+:Mg2+ [cytosol] (Homo sapiens)
Activity
glutathione synthase activity (GO:0004363)
Normal reaction
GSS:Mg2+ dimer synthesizes GSH (Homo sapiens)
Functional status

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

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
inherited metabolic disorder DOID:655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
Authored
Jassal, B  (2014-06-25)
Reviewed
Nakaki, T  (2014-11-03)
Created
Jassal, B  (2014-06-25)
Cite Us!