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6.3.2.2: glutamate-cysteine ligase

This is an abbreviated version!
For detailed information about glutamate-cysteine ligase, go to the full flat file.

Word Map on EC 6.3.2.2

Reaction

ATP
+
L-glutamate
 +
L-cysteine
=
ADP
 +
phosphate
 +
gamma-L-glutamyl-L-cysteine

Synonyms

Ace-GCL, Asuc_1947, AtGCL, bifunctional glutathione synthetase, bifunctional GSH synthetase, bifunctional L-glutathione synthetase, gamma -GCS, gamma-ECL, Gamma-ECS, gamma-GC, gamma-GCS, gamma-GCS-GS, gamma-glutamate-cysteine ligase-glutathione synthetase, gamma-glutamate-cysteine ligase/glutathione synthetase, gamma-glutaminylcysteine synthetase, gamma-glutamycysteine synthetase, gamma-glutamyl-cysteine ligase, gamma-Glutamyl-L-cysteine synthetase, gamma-glutamylcysteine ligase, gamma-glutamylcysteine synthase, gamma-Glutamylcysteine synthetase, gamma-glutamylcysteine synthetase-glutathione synthetase, gamma-Glutamylcysteinyl-synthetase, gammaGCS, GCL, GCLC, Gclc-X2, GCLM, GCS, GCSGS, ghF, GLCL, GLCLC, GLCLR, glutamate cysteine ligase, glutamate cysteine ligase gene, glutamate-cysteine ligase, glutamate-cysteine-ligase, glutamatecysteine ligase, glutathione biosynthesis bifunctional protein GshAB, GSH1, GshA, gshAB, GshF, GshFAp, GshFAs, GSHI, I79_022778, L-glutamate L-cysteine ligase, More, PAD2, PhGshA II, PSHAa0937, StGCL-GS, Synthetase, gamma-glutamylcysteine

ECTree

     6 Ligases
         6.3 Forming carbon-nitrogen bonds
             6.3.2 Acid—amino-acid ligases (peptide synthases)
                6.3.2.2 glutamate-cysteine ligase

Expression

Expression on EC 6.3.2.2 - glutamate-cysteine ligase

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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
actinomycin D and cycloheximide suppress enzyme expression
actinomycin D and cycloheximide suppress enzyme expression. Using GCLC knockout murine embryonic fibroblasts, addition of cysteine to catalytic subunit GCLC null cells results in a marked decrease in regulatory subunit GCLM mRNA levels despite the absence of GSH. Addition of GSH similarly reduces GCLM mRNA abundance
-
As3+ coordinately upregulates GCL catalytic subunit and GCL modifier subunit mRNA levels resulting in increased GCL subunit protein expression, holoenzyme formation, and activity. As3+ increases the rate of transcription of both the GCL catalytic subunit and GCL modifier subunit genes and induces the posttranscriptional stabilization of GCL modifier subunit mRNA. The antioxidant N-acetylcysteine abolishes As3+-induced GCL catalytic subunit expression and attenuates induction of GCL modifier subunit. As3+ induction of GCL catalytic subunit and GCL modifier subunit is also differentially regulated by the MAPK signaling pathways and occurs independent of the Nrf1/2 transcription factors
-
both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels
-
both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. In liver of rats fed sulfur amino acid-deficient diets, induction of ATF4 and phosphorylation of eIF2alpha are associated with higher levels of GCLC and GCLM mRNA
both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. The upregulation does not occur in MEFs lacking GCN2, i.e. general control non-derepressible 2, also known as eIF2a kinase 4, or in cells expressing mutant eIF2alpha lacking the eIF2alpha kinase Ser51 phosphorylation site, indicating that expression of both GCLC and GCLM is mediated by the GCN2/ATF4 stress response pathway
-
catalytic subunit GCLC protein levels do not increase, whereas regulatory subunit GCLM protein levels increase in the cells cultured in cysteine-deficient medium
-
enzyme induction in macrophages by beta-carotene or beta-cryptoxanthin. Both the protein and mRNA expression of GCL increases in a beta-carotene concentration-dependent manner. Buthionine sulfoximine, a GCL inhibitor, abolishes the beta-carotene-induced GSH increase without affecting the beta-carotene-induced GCL protein expression. Both cycloheximide, a translation inhibitor, and actinomycin D, a transcription inhibitor, completely suppressed the beta-carotene-induced GCL protein expression and the concomitant GSH increase. Similarly to beta-carotene, beta-cryptoxanthin upregulates the GCL protein expression, but lutein does not. The c-Jun N-terminal kinase (JNK) inhibitor, SP600125, suppresses the beta-carotene-induced GSH increase, whereas a p38 mitogen-activated protein kinase inhibitor or an extracellular signal-regulated kinase 1/2 inhibitor do not. The JNK inhibitor also suppresses the beta-carotene-induced GCL protein expression and consistently beta-carotene induced JNK phosphorylation
P97494; O09172
fibroblast growth factor 9 treatment alone induces a decrease in hydrogen peroxide level, an increase in glutathione content, and an upregulation of gamma-glutamylcysteine synthetase and heme oxygenase 1 expression in primary cortical neurons but not in astrocytes. Simultaneous treatmentwith fibroblast growth factor 9 and 1-methyl-4-phenylpyridinium prevents 1-methyl-4-phenylpyridinium-induced neuron death and H2O2 overproduction but does not affect the fibroblast growth factor 9-increased gamma-GCS and HO-1 protein expression
-
GshA gene when expressed in an Escherichia coli strain lacking functional GshA is able to restore synthesis of glutathione
in interscapular brown adipose tissue, nitric oxide induces in vivo glutathione synthesis through activation of glutamate-cysteine ligase mRNA and protein expression. This effect appears to be mediated by nuclear factor kappaB activation
-
indomethacin inhibits the gamma-glutamylcysteine synthetase promoter activity. Co-treatment by indomethacin and doxorubicin increases the cytotoxicitiy of doxorubicin by decreasing the intracellular contents of glutathione and its conjugates with decreasing expression of gamma-glutamylcysteine synthetase
-
kaempferol protects cells against cisplatin-induced apoptosis in a dose-dependent manner in HEI-OC1 cells. Kaempferol increases the cellular level of glutathione and the expression of GCL catalytic subunit time-dependently. siRNA directed against GCL catalytic subunit blocks the increase of glutathione level by kaempferol and the protective effect of kaempferol against cisplatin-induced cell death
-
oncogen MYCN directly binds to an E-box containing GCL catalytic subunit promoter and over-expression of MYCN in MYCN-non-amplified cells stimulates GCL catalytic subunit expression and provides resistance to oxidative damage. Knock-down of MYCN in MYCN-amplified cells decreases GCL catalytic subunit expression and sensitizes them to oxidative damage
-
presence of an ethanol-responsive element in the human GCL catalytic subunit promoter, it spannes bases 1432 to 832 in hepatocytes and HepG2 cells transfected with cytochrome P450 2E1. The region lacks an ARE but has a putative nuclear factor-kappaB element
-
red ginseng extract upregulates catalytic subunit of GCL and heme oxydase-1. Heme oxidase-1 and GCL catalytic subunit induction via Nrf2 activation may contribute to cytoprotection exerted by red ginseng extract against PCB126-induced oxidative stress
-
specific downregulation of the GCL levels by hammerhead ribo­zyme