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Literature summary for 6.3.2.3 extracted from
- Regulation of glutathione synthesis (2008), Mol. Aspects Med., 30, 42-59.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| monocrotaline | treatment of rats with monocrotaline, a pyrrolizidine alkaloid, increases the activity of GS | Rattus norvegicus |  |
| additional information | oxidative stress induces the enzyme, key transcription factors include Nrf2/Nrf1 via the antioxidant response element, ARE, activator protein-1, AP-1, and nuclear factor kappa B, NFkappaB. Basal expression requires AP-1 and NFkappaB | Rattus norvegicus | |
| additional information | oxidative stress induces the enzyme, key transcription factors include Nrf2/Nrf1 via the antioxidant response element, ARE, activator protein-1, AP-1, and nuclear factor kappa B, NFkappaB. Nrf1 and Nrf2 overexpression induces the human GS promoter activity | Homo sapiens | |
| additional information | oxidative stress induces the enzyme, key transcription factors include Nrf2/Nrf1 via the antioxidant response element, ARE, activator protein-1, AP-1, and nuclear factor kappa B, NFkappaB. Nrf1 is required for basal expression of GS in the mouse | Mus musculus |
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | the enzyme is a target for therapy of disease like diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells, since manipulation of the GSH synthetic capacity is beneficial in treatment of many of these disorders | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| cloning of the enzyme promoter and molecular mechanisms of GS transcriptional regulation, overview. Nrf1 and Nrf2 overexpression induces the human GS promoter activity. Human GS promoter contains two regions with homology to the nuclear factor erythroid 2, NFE2, motif that are required for basal activity as mutation of these sites reduces the human GS promoter activity by 66% | Homo sapiens |
| cloning of the enzyme promoter and molecular mechanisms of GS transcriptional regulation. The rat GS promoter contains functional AP-1 sites, some of which act as enhancers. It also contains a functional NF1 site that acts as a repressor, and basal expression requires AP-1 and NFkappaB, overview | Rattus norvegicus |
| Nrf1 is required for basal expression of GS in the mouse | Mus musculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | decreased hepatic GSH levels occur, which correlated with a fall in GS activity, in Tat transgenic mice. GCLC and GS are coordinately regulated but GCLM is unchanged in liver-specific retinoid X receptor alpha knockout mice | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Mus musculus | 5829 | - |
| cytosol | - |
Homo sapiens | 5829 | - |
| cytosol | - |
Rattus norvegicus | 5829 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | - |
Mus musculus | |
| Mg2+ | - |
Homo sapiens | |
| Mg2+ | - |
Rattus norvegicus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + gamma-L-glutamyl-L-cysteine + glycine | Homo sapiens | glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | Rattus norvegicus | glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | Mus musculus | glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview. Changes in GSH homeostasis occur in mice with liver-specific retinoid X receptor RXRalpha deletion | ADP + phosphate + glutathione | - |
? | |
| additional information | Mus musculus | dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells | ? | - |
? | |
| additional information | Rattus norvegicus | dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells | ? | - |
? | |
| additional information | Homo sapiens | dysregulation of GSH synthesis occurs in aging and is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells, detailed overview. Decrease in the activity of GS alone without a change in glutathione cysteine ligase, GCL EC 6.3.2.2, and a fall in muscle GSH levels occur after surgical trauma in human skeletal muscle | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| liver | - |
Mus musculus | - |
| liver | - |
Homo sapiens | - |
| liver | - |
Rattus norvegicus | - |
| skeletal muscle | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + gamma-L-glutamyl-L-cysteine + glycine | - |
Mus musculus | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | - |
Homo sapiens | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | - |
Rattus norvegicus | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview | Homo sapiens | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview | Rattus norvegicus | ADP + phosphate + glutathione | - |
? | |
| ATP + gamma-L-glutamyl-L-cysteine + glycine | glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview. Changes in GSH homeostasis occur in mice with liver-specific retinoid X receptor RXRalpha deletion | Mus musculus | ADP + phosphate + glutathione | - |
? | |
| additional information | dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells | Mus musculus | ? | - |
? | |
| additional information | dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells | Rattus norvegicus | ? | - |
? | |
| additional information | dysregulation of GSH synthesis occurs in aging and is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells, detailed overview. Decrease in the activity of GS alone without a change in glutathione cysteine ligase, GCL EC 6.3.2.2, and a fall in muscle GSH levels occur after surgical trauma in human skeletal muscle | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| GSH synthase | - |
Mus musculus |
| GSH synthase | - |
Homo sapiens |
| GSH synthase | - |
Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Mus musculus | |
| ATP | - |
Homo sapiens | |
| ATP | - |
Rattus norvegicus | |
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