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)).e1aDPEP1e5ed5cbddd5cd5cbdda50f7ae5ecc7d5cbdef7acc3cc7f87bdd29483667PubMedγ-glutamyl transpeptidase deficiency caused by a large homozygous intragenic deletion in GGT1.Eur J Hum Genet2018Darin NLeckström KSikora PLindgren J Almén GAsin-Cayuela Jglutathione metabolic pathwayPW:0000134Pathway Ontologyhemolytic anemiaDOID:583Disease6113726PubMed5-oxoprolinuria due to hereditary 5-oxoprolinase deficiency in two brothers--a new inborn error of the gamma-glutamyl cycle.Acta Paediatr Scand1981Larsson AMattsson BWauters EAvan Gool JDDuran MWadman SK16618936PubMedCrystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate.Proc Natl Acad Sci U S A2006Okada TSuzuki HWada KKumagai HFukuyama K4152248PubMedGlutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria).Proc Natl Acad Sci U S A1974Wellner VPSekura RMeister ALarsson Aamino acid metabolic pathwayPW:0000011Pathway Ontology7937585PubMedPrenatal diagnosis of glutathione synthase deficiency.Prenat Diagn1994Manning NJDavies NPOlpin SECarpenter KHSmith MFPollitt RJDuncan SLLarsson ACarlsson Bdisease pathwayPW:0000013Pathway Ontologyglutathione biosynthetic pathwayPW:0001277Pathway Ontology9783642403361PubMedPhysician's Guidee to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases'ISBN 978-3-64240337-82014BlauNenadDuranMarinusGibson, KMichaelDionisi-ViciCarlo8127060PubMed5-Oxoprolinuria associated with 5-oxoprolinase deficiency; further evidence that this is a benign disorder.J Inherit Metab Dis1993Henderson MJLarsson ACarlsson BDear PR8099811PubMedExtracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase.Biochemistry1993Hanigan MHRicketts WA238530PubMedGlutathionuria: inborn error of metabolism due to tissue deficiency of gamma-glutamyl transpeptidase.Biochem Biophys Res Commun1975Schulman JDGoodman SIMace JWPatrick ADTietze FButler EJglutathionuria disease pathwayPW:0002562Pathway Ontology4152527PubMedThe gamma-glutamyl cycle. Diseases associated with specific enzymedeficiencies.Ann Intern Med1974Meister A10515893PubMedThe molecular basis of a case of gamma-glutamylcysteine synthetase deficiency.Blood1999Beutler EGelbart TKondo TMatsunaga AT8810901PubMedA pseudo-michaelis quaternary complex in the reverse reaction of a ligase: structure of Escherichia coli B glutathione synthetase complexed with ADP, glutathione, and sulfate at 2.0 A resolution.Biochemistry1996Hara TKato HKatsube YOda J15717202PubMedGenotype, enzyme activity, glutathione level, and clinical phenotype in patients with glutathione synthetase deficiency.Hum Genet2005Njålsson RRistoff ECarlsson KWinkler ALarsson ANorgren Sgamma-glutamyl transpeptidase deficiencyDOID:0111257Disease5289242PubMedEnzymatic conversion of 5-oxo-L-proline (L-pyrrolidone carboxylate) to L-glutamate coupled with cleavage of adenosine triphosphate to adenosine diphosphate, a reaction in the -glutamyl cycle.Proc Natl Acad Sci U S A1971Van der Werf POrlowski MMeister A11445798PubMedLong-term clinical outcome in patients with glutathione synthetase deficiency.J Pediatr2001Ristoff EMayatepek ELarsson Aautosomal recessive diseaseDOID:0050737Diseasemetabolic acidosisDOID:0050758Disease18515354PubMedThe identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle.J Biol Chem2008Oakley AJYamada TLiu DCoggan MClark AGBoard PG2294991PubMedGamma-glutamylcysteine synthetase deficiency and hemolytic anemia.Blood1990Beutler EMoroose RKramer LGelbart TForman L