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

Stable Identifier
Reaction [transition]
Homo sapiens
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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
12663448 A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production

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

Blood 2003
10515893 The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency

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

Blood 1999
10733484 A missense mutation in the heavy subunit of gamma-glutamylcysteine synthetase gene causes hemolytic anemia

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

Blood 2000
Catalyst Activity

glutamate-cysteine ligase activity of GCLC mutants:GCLM [cytosol]

Normal reaction
Functional status

Loss of function of GCLC mutants:GCLM [cytosol]

Name Identifier Synonyms
hemolytic anemia DOID:583 Hemolytic anemias (disorder), Hemolytic anemia (disorder), Hemolytic anemias NOS (disorder), hemolytic anemia, ANEMIA HEMOLYTIC
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