Defective GGT1 causes Glutathionuria (GLUTH)

Stable Identifier
R-HSA-9035968
Type
Pathway
Species
Homo sapiens
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To be excreted in urine, glutathione conjugates undergo several hydrolysis steps to form mercapturic acids which are readily excreted. The first step is the hydrolysis of a gamma-glutamyl residue from the conjugate catalysed by gamma-glutamyltransferases (GGTs). These are membrane-bound, heterodimeric enzymes composed of light and heavy peptide chains. Extracellular glutathione (GSH) or its conjugates can be hydrolysed to give cysteinylglycine (CG, or CG conjugates) and free glutamate (L-Glu). Hydrolysis of GSH provides cells with a local cysteine supply and contributes to intracellular GSH levels (Heisterkamp et al. 2008). Defects in GGT1 can cause glutathionuria (GLUTH; MIM:231950), an autosomal recessive disorder characterised by increased GSH concentration in the plasma and urine. Mutations that cause GLUTH can occur in both chains of the GGT1 dimer (Heisterkamp et al. 2008, Aoyama & Nakaki 2013).

Literature References
PubMed ID Title Journal Year
24145751 Impaired glutathione synthesis in neurodegeneration

Aoyama, K, Nakaki, T

Int J Mol Sci 2013
18357469 The human gamma-glutamyltransferase gene family

Heisterkamp, N, Groffen, J, Warburton, D, Sneddon, TP

Hum Genet 2008
Participants
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Disease
Name Identifier Synonyms
inherited metabolic disorder 655 Metabolic hereditary disorder, Inborn Errors of Metabolism, inborn metabolism disorder
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