Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as leukotriene C4, LTC4) (PubMed:17924658, PubMed:21447318, PubMed:27791009). The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases (PubMed

Cell membrane

Glutathionuria

A very rare, autosomal recessive metabolic disorder characterized by the presence of glutathione in the urine, due to generalized gamma-glutamyl transpeptidase deficiency. Most patients manifest mild to moderate intellectual disability, and behavioral disturbance. Seizures, tremor, marfanoid features and strabismus are observed in some patients.

Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (PubMed:40281343). Can also reduce cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (PubMed:40281343). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive

MitochondrionCytoplasm

Spondylometaphyseal dysplasia, Sedaghatian type

A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDS is a neonatal lethal form characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, cardiac conduction defects, and central nervous system abnormalities.

Catalyzes the cleavage of 5-oxo-L-proline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate

Cytoplasm, cytosol

5-oxoprolinase deficiency

A disorder characterized by calcium oxalate/carbonate urolithiasis, and excessive urinary 5-oxo-L-proline. Affected individuals have recurrent episodes of vomiting, diarrhea, and abdominal pain.

Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis

Anemia, congenital, non-spherocytic hemolytic, 7

An autosomal recessive disease characterized by hemolytic anemia, glutathione deficiency, myopathy, late-onset spinocerebellar degeneration, and peripheral neuropathy.

Catalyzes the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH). Constitutes the major mechanism to maintain a high GSH:GSSG ratio in the cytosol

MitochondrionCytoplasm

Anemia, congenital, non-spherocytic hemolytic, 10

An autosomal recessive disease characterized by hemolytic anemia and impaired activity of glutathione reductase. Patients experience hemolytic anemia in response to oxidative stress or ingestion of fava beans.

Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner (PubMed:7646467, PubMed:9215686). Glutathione (gamma-glutamylcysteinylglycine, GSH) is the most abundant intracellular thiol in living aerobic cells and is required for numerous processes including the protection of cells against oxidative damage, amino acid transport, the detoxification of foreign compounds, the maintenance of protein sulfhydryl groups in a reduced state and acts as a cofa

Glutathione synthetase deficiency

An autosomal recessive disorder characterized by massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia, and central nervous system damage.