Defective GCLC causes Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency (HAGGSD)

Stable Identifier
R-HSA-5578999
Type
Pathway
Species
Homo sapiens
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In mammalian cells, many antioxidant defence systems exist which protect cells from subsequent exposure to oxidant stresses. One antioxidant is glutathione (GSH), a tripeptide present in virtually all cells that regulates the intracellular redox state and protects cells from oxidative injury. It is metabolised via the gamma-glutamyl cycle, which is catalysed by six enzymes. In man, hereditary deficiencies have been found in five of the six enzymes. 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 (Ristoff & Larsson 2007, Aoyama & Nakaki 2013).

Literature References
PubMed ID Title Journal Year
17397529 Inborn errors in the metabolism of glutathione

Ristoff, E, Larsson, A

Orphanet J Rare Dis 2007
24145751 Impaired glutathione synthesis in neurodegeneration

Aoyama, K, Nakaki, T

Int J Mol Sci 2013
Participants
Participant Of
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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