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Glutamate-Cysteine Ligase

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One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2.

Also Known As:

Glutamylcysteine Synthetase; Glutamate Cysteine Ligase; Ligase, Glutamate-Cysteine; Synthetase, Glutamylcysteine; Synthetase, gamma-Glutamyl-Cysteine; gamma Glutamyl Cysteine Synthetase; gamma-Glutamyl-Cysteine Synthetase; L-Glutamate:L-cysteine gamma-ligase (ADP-forming)

Networked: 110 relevant articles (1 outcomes, 17 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Enzymes and Coenzymes
- Enzymes: 34502
  - Ligases: 2113
    - Carbon-Nitrogen Ligases
      - Peptide Synthases: 6
        Glutamate-Cysteine Ligase: 110
        human glutamate-cysteine ligase modifier subunit: 2
        Arabidopsis Gsh1 protein
        rat GCLC protein
        S cerevisiae GSH1 protein

Experts

1.	Kavanagh, Terrance J: 6 articles (07/2013 - 06/2006)
2.	Cuénod, Michel: 5 articles (10/2011 - 09/2006)
3.	Do, Kim Q: 5 articles (10/2011 - 10/2007)
4.	Kugiyama, Kiyotaka: 4 articles (02/2013 - 02/2003)
5.	Fujioka, Daisuke: 3 articles (02/2013 - 09/2003)
6.	Gysin, René: 3 articles (10/2011 - 10/2007)
7.	Preisig, Martin: 3 articles (10/2011 - 09/2006)
8.	Bovet, Pierre: 3 articles (10/2011 - 09/2006)
9.	Werge, Thomas: 3 articles (08/2009 - 09/2006)
10.	Abe, Yoshiyuki: 3 articles (08/2005 - 11/2003)

Related Diseases

1.	Contusions 03/20/2012 - "Treatment of injured rats with sulforaphane, an activator of Nrf2/ARE signaling, significantly increased levels of Nrf2 and glutamate-cysteine ligase (GCL), a rate-limiting enzyme for synthesis of glutathione, and decreased levels of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) thus leading to a reduction in contusion volume and improvement in coordination. "
2.	Schizophrenia (Dementia Praecox) 10/01/2009 - "Association and expression studies of glutamate-cysteine ligase modifier (GCLM) and schizophrenia in the Chinese Han population." 04/06/2009 - "Genetic studies revealed an association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the catalytic subunit (GCLC) of the glutamate cysteine ligase (GCL). " 09/01/2006 - "The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. " 01/01/2011 - "In particular, a polymorphism in the gene of glutamate cysteine ligase modulatory subunit (GCLM) is associated with schizophrenia. " 06/01/2010 - "Genetic analysis of glutamate cysteine ligase modifier (GCLM) gene and schizophrenia in Han Chinese."
3.	Breast Neoplasms (Breast Cancer) 11/01/2013 - "To investigate the interaction of body mass index(BMI)and a single nucleotide polymorphism (SNP, rs17883901) in catalytic subunit of glutamate-cysteine ligase (GCLC) on breast cancer risk. " 11/01/2013 - "[Interaction of body mass index and a polymorphism in gene of catalytic subunit of glutamate-cysteine ligase on breast cancer risk among Chinese women]." 08/15/2011 - "In the present study, treatment of human breast cancer MCF-7 cells with 15d-PGJ(2) caused the up-regulation of the glutamate cysteine ligase catalytic (GCLC) subunit, the rate-limiting enzyme in glutathione (GSH) synthesis. " 02/09/2012 - "The optimal structure, 2-chloro-4',6'-dimethoxy-2'-hydroxychalcone, induced both a potent NF-E2-related factor 2-mediated transcriptional response and an increased formation of glutamate cysteine ligase holoenzyme, as shown using a human breast cancer cell line stably expressing a luciferase reporter gene driven by antioxidant response elements." 08/15/2011 - "Multidrug resistance-associated protein 1 mediates 15-deoxy-Δ(12,14)-prostaglandin J2-induced expression of glutamate cysteine ligase expression via Nrf2 signaling in human breast cancer cells."
4.	Neoplasms (Cancer) 09/01/2007 - "Manipulation of intracellular GSH content through pharmacological inhibition of glutamate-cysteine ligase (GCL) indicated that GSH depletion potentiated nitrosative stress, DNA damage, phosphorylation of the tumor suppressor p53 (Ser-18) and upregulation of p21(cip1/waf1) upon NO stimulation. " 01/01/2003 - "Therefore, elevation of GSH as achieved by inducing g-glutamylcysteine synthetase (GCS), the limiting enzyme of GSH synthesis, may contribute to chemoprevention against cancer. " 01/01/2014 - "Glucocorticoid receptor (GCR) knockdown decreased the expression and activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting step in GSH synthesis, in metastatic cells in vivo independent of the tumor location (liver, lung, or subcutaneous). " 01/01/2003 - "Retroviral transfer of MRP1 and gamma-glutamyl cysteine synthetase modulates cell sensitivity to L-buthionine-S,R-sulphoximine (BSO): new rationale for the use of BSO in cancer therapy." 01/01/2014 - "In an in vitro study, the expression of the genes glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS) that synthesize GSH and GSH-Px gene were verified by qPCR and subjected to treatment with doxorubicin, to check the resistance of cancer cells to chemotherapy. "
5.	Anoxia (Hypoxia) 02/01/2010 - "Hypoxia decreased 2 key enzyme activities that regulate GSH synthesis, glutamate cysteine ligase (GCL) (E.C. " 02/01/2008 - "To measure the effect of hypoxia among different organs, total glutathione (GSH) content and protein levels of gamma-glutamyl cysteine synthetase (gamma-GCS) were measured from the same organs. " 02/01/2008 - "Chronic hypoxia differentially increases glutathione content and gamma-glutamyl cysteine synthetase expression in fetal guinea pig organs." 01/01/2011 - "RNAi-mediated knockdown of key GSH regulatory enzymes γ-glutamylcysteine synthetase or glutathione disulfide reductase partially reversed the hypoxia-induced resistance to fenretinide, and increasing GSH levels using N-acetylcysteine augmented the hypoxia-induced resistance in a cell line-specific manner. " 07/01/2015 - "In cultured Müller cells, flow cytometry for dihydroethidium revealed that ebselen reduced the hypoxia-induced increase in ROS levels, whilst increasing the expression of Nrf2-regulated anti-oxidant genes, heme oxygenase 1, glutathione peroxidase-1, NAD(P)H dehydrogenase quinone oxidoreductase 1 and glutamate-cysteine ligase. "

Related Drugs and Biologics

1.	Glutathione (Reduced Glutathione)
2.	Cytokines
3.	Tumor Necrosis Factor-alpha (Tumor Necrosis Factor)
4.	sulforafan (sulforaphane)
5.	Superoxide Dismutase
6.	Glutathione Transferase (Glutathione S-Transferase)
7.	Enzymes
8.	Glutathione Reductase (Glutathione-Disulfide Reductase)
9.	Catalase
10.	Heme Oxygenase-1

Related Therapies and Procedures

1.	Drug Therapy (Chemotherapy)
2.	Heterologous Transplantation (Xenotransplantation)
3.	Chemoprevention