Gamma-glutamyl cycle for the biosynthesis and degradation of glutathione, including diseases (WP4518)

Homo sapiens

This pathway shows diseases related to the biosynthesis and degradation of glutathione. Diseases resulting from an enzyme deficiency are highlighted in pink. The four genetic defects, causing the diseases, are all inherited as autosomal recessive traits. All patients with gamma-glutamylcysteine synthetase deficiency are diagnosed with hemolytic anemia. Glutathione synthetase deficiency is classified in mild, moderate and severe. Patient diagnosed with mild glutathione synthetase deficiency suffer from hemolytic anemia only, while patient with the moderate and severe form show neurological symptoms, metabolic acidosis and bacterial infections as well. This pathway was inspired by Chapter 42 of the book of Blau (ISBN 3642403360 (978-3642403361)).


Lobke Meels , Denise Slenter , Eline Sanders , Irene Hemel , Egon Willighagen , Friederike Ehrhart , Eric Weitz , and Finterly Hu


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Pathway Ontology

glutathione metabolic pathway amino acid metabolic pathway disease pathway glutathione biosynthetic pathway glutathionuria disease pathway

Disease Ontology

hemolytic anemia gamma-glutamyl transpeptidase deficiency autosomal recessive disease metabolic acidosis


Label Type Compact URI Comment
Glutamate Metabolite chebi:14321
Glycine Metabolite chebi:15428
L-gamma-glutamyl amino acid Metabolite chebi:15857
ATP Metabolite chebi:15422
ADP Metabolite chebi:16761
ADP Metabolite chebi:16761
Amino acid Metabolite chebi:33704
Cysteine Metabolite chebi:15356
Glutathione Metabolite chebi:16856
5-Oxoproline Metabolite chebi:16010
Gamma-glutamylcysteine Metabolite chebi:17515
ATP Metabolite chebi:15422
Cysteinylglycine Metabolite chebi:4047
ADP Metabolite chebi:16761
ATP Metabolite chebi:15422
Amino acid Metabolite chebi:33704
Glutamate Metabolite chebi:14321
GGT1 Protein uniprot:P19440
GSS Protein uniprot:P48637
5-Oxoprolinase Protein uniprot:O14841
GGCT Protein uniprot:O75223
GCLC Protein uniprot:P48506
Dipeptidase Protein uniprot:P16444 DPEP1


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  15. The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle. Oakley AJ, Yamada T, Liu D, Coggan M, Clark AG, Board PG. J Biol Chem. 2008 Aug 8;283(32):22031–42. PubMed Europe PMC Scholia
  16. γ-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1. Darin N, Leckström K, Sikora P, Lindgren J, Almén G, Asin-Cayuela J. Eur J Hum Genet. 2018 Jun;26(6):808–17. PubMed Europe PMC Scholia
  17. Pubmed: 9783642403361