Defective GCLC does not ligate L-Glu to L-Cys

Stable Identifier
R-HSA-5602892
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Gamma-glutamylcysteine ligase (GCL) catalyses the first and rate-limiting step in GSH biosynthesis. GCL is a heterodimer of a catalytic heavy chain (GCLC) and a regulatory light chain (GCLM). Defects in the catalytic GCLC can cause hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD; MIM:230450), a disease characterised by hemolytic anemia, glutathione deficiency, myopathy, late-onset spinocerebellar degeneration, and peripheral neuropathy. Mutations causing HAGGSD are H370L, P185L and R127C (Beutler et al. 1999, Ristoff et al. 2000, Hamilton et al. 2003).

Literature References
PubMed ID Title Journal Year
10515893 The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency

Beutler, E, Gelbart, T, Kondo, T, Matsunaga, AT

Blood 1999
12663448 A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production

Hamilton, D, Wu, JH, Alaoui-Jamali, M, Batist, G

Blood 2003
10733484 A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia

Ristoff, E, Augustson, C, Geissler, J, de Rijk, T, Carlsson, K, Luo, JL, Andersson, K, Weening, RS, van Zwieten, R, Larsson, A, Roos, D

Blood 2000
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
glutamate-cysteine ligase activity of GCLC mutants:GCLM [cytosol]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
hemolytic anemia 583 Hemolytic anemias (disorder), Hemolytic anemia (disorder), Hemolytic anemias NOS (disorder), hemolytic anemia, ANEMIA HEMOLYTIC
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Reviewed
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