Information on EC 6.3.2.2 - Glutamate-cysteine ligase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY
6.3.2.2
-
RECOMMENDED NAME
GeneOntology No.
Glutamate-cysteine ligase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
partially random mechanism in which ATP is the obligatory first substrate and both amino acids bind in a random order to the enzyme*ATP complex. Formation of the enzyme*substrate quarternary complex is necessary prior to release of products
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
bi bi uni uni ping pong mechanism, with glutamyl-enzyme as intermediate before the addition of cys and the release of gamma-glutamylcysteine
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
tri tri sequential mechanism
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
reaction mechanism
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Cys553 is not the active site residue
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, catalytic mechanism and substrate binding
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, catalytic mechanism, active site and substrate binding, Lys38 is an active site residue in the glutamyl binding site, His150 is essential for activity
P19468, P48508
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism
P48506, P48507
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
enzyme-bound reaction intermediate is a gamma-glutamyl-phosphate, active site cysteine, mechanism
P97494, Q97SC0
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
no conserved cysteine residue in the active site
P0A6W9
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
no conserved cysteine residue in the active site
P90557
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
rapid equilibrium random ter-reactant mechanism, substrate binding modeling, active site model
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
rapid equilibrium random ter-reactant mechanism, substrate binding modeling, Cys319 is an active site cysteine not essential for activity, reaction and kinetic mechanism, modeling
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
reaction mechanism via phosphorylated glutamate intermediate
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
substrate binding mechanism and catalytic site structure determination and analysis, Arg127 and conserved Cys249 are involved
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
reaction mechanism, overview
P74515
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
reaction mechanism
Escherichia coli JM109
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
ergothioneine biosynthesis I (bacteria)
-
-
glutathione biosynthesis
-
-
Glutathione metabolism
-
-
glutathione metabolism
-
-
homoglutathione biosynthesis
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
L-Glutamate:L-cysteine gamma-ligase (ADP-forming)
Can use L-aminohexanoate in place of glutamate.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Gamma-ECS
-
-
-
-
gamma-Glutamyl-L-cysteine synthetase
-
-
-
-
gamma-Glutamylcysteine synthetase
-
-
-
-
gamma-Glutamylcysteinyl-synthetase
-
-
-
-
GCS
-
-
-
-
Synthetase, gamma-glutamylcysteine
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9023-64-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
symbiotic sea anemone, genes gclC and gclM encoding the catalytic and the modifier subunits of the enzyme
UniProt
Manually annotated by BRENDA team
mallard duck
-
-
Manually annotated by BRENDA team
Bacterium cadaveris
-
-
-
Manually annotated by BRENDA team
enriched by recombinant DNA techniques in its content of gamma-glutamylcysteine synthetase, strain W, strain KM
-
-
Manually annotated by BRENDA team
gene gshA
-
-
Manually annotated by BRENDA team
K12, strain W3110, gene gshI
-
-
Manually annotated by BRENDA team
strain B
-
-
Manually annotated by BRENDA team
strain B; strain Crooks; strain FKU-1; strain FKU-3; strain FKU-8; strain K-10; strain K-12; strain S-96
-
-
Manually annotated by BRENDA team
strain B; wild-type and mutant enzyme His150Ala
-
-
Manually annotated by BRENDA team
strain JM109
SwissProt
Manually annotated by BRENDA team
strain W, strain B, strain KM
SwissProt
Manually annotated by BRENDA team
Escherichia coli Crooks
strain Crooks
-
-
Manually annotated by BRENDA team
Escherichia coli FKU-1
strain FKU-1
-
-
Manually annotated by BRENDA team
Escherichia coli FKU-3
strain FKU-3
-
-
Manually annotated by BRENDA team
Escherichia coli FKU-8
strain FKU-8
-
-
Manually annotated by BRENDA team
Escherichia coli JM109
strain JM109
SwissProt
Manually annotated by BRENDA team
Escherichia coli K-10
strain K-10
-
-
Manually annotated by BRENDA team
Escherichia coli S-96
strain S-96
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
2 subunits encoded by 2 genes
-
-
Manually annotated by BRENDA team
activity of the gamma-glutamylcysteine synthetase promoter decreases after indomethacin treatment; leukemia cell. Cells show increased expression of gamma-glutamylcysteine synthetase. Expression decreases by indomethacin treatment
-
-
Manually annotated by BRENDA team
enzyme consists of a catalytic GCLC and a modulatory GCLM subunit encoded by 2 separate gcl genes
-
-
Manually annotated by BRENDA team
gene gclC and gclM encoding the two subunits of the enzyme
-
-
Manually annotated by BRENDA team
genes gclC and gclM encoding the two subunits of the enzyme
-
-
Manually annotated by BRENDA team
healthy individuals and chronic obstructive pulmonary disease patients, genes gclC and gclM encoding the two subunits of the enzyme
-
-
Manually annotated by BRENDA team
heavy, catalytic subunit
SwissProt
Manually annotated by BRENDA team
Japanese individuals and patients with methamphetamine dependence and induced psychosis, genes gclC and gclM encoding the catalytic and the modifier subunit of the enzyme
-
-
Manually annotated by BRENDA team
light, regulatory subunit
SwissProt
Manually annotated by BRENDA team
patients with non-alcoholic steatohepatitis
-
-
Manually annotated by BRENDA team
strain KTCC 2386, gene gshA
-
-
Manually annotated by BRENDA team
Leuconostoc kimchii KTCC 2386
strain KTCC 2386, gene gshA
-
-
Manually annotated by BRENDA team
strain ATCC8293, gene gshA
-
-
Manually annotated by BRENDA team
Leuconostoc mesenteroides ATCC8293
strain ATCC8293, gene gshA
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
2 subunits encoded by 2 genes
-
-
Manually annotated by BRENDA team
deer mice
-
-
Manually annotated by BRENDA team
gene gclC and gclM, encoding the catalytic and the modifier subunit
-
-
Manually annotated by BRENDA team
genes gclC and gclM
-
-
Manually annotated by BRENDA team
genes gclC and gclM encoding the two subunits of the enzyme
-
-
Manually annotated by BRENDA team
heavy, catalytic subunit
SwissProt
Manually annotated by BRENDA team
light, regulatory subunit
SwissProt
Manually annotated by BRENDA team
no activity in Entamoeba histolytica
-
-
-
Manually annotated by BRENDA team
no activity in Giardia sp.
-
-
-
Manually annotated by BRENDA team
PCC 7120
-
-
Manually annotated by BRENDA team
hybrid, INRA-clone Nr. 717-1-B4
-
-
Manually annotated by BRENDA team
wild-type and overexpressing gamma-glutamylcysteine synthetase
-
-
Manually annotated by BRENDA team
Pseudomonas schuylkilliensis
-
-
-
Manually annotated by BRENDA team
2 subunits encoded by 2 genes
-
-
Manually annotated by BRENDA team
catalytic subunit
SwissProt
Manually annotated by BRENDA team
female Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
genes gclC and gclM encoding the two subunits of the enzyme
-
-
Manually annotated by BRENDA team
heavy, catalytic subunit
SwissProt
Manually annotated by BRENDA team
light, regulatory subunit
SwissProt
Manually annotated by BRENDA team
male F344 rats
-
-
Manually annotated by BRENDA team
male Lewis rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats, genes GCLC and GCLM
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-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats, female
SwissProt
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
bifunctional glutamate-cysteine ligase and glutathione synthetase
UniProt
Manually annotated by BRENDA team
Streptococcus thermophilus SIIM B218
bifunctional glutamate-cysteine ligase and glutathione synthetase
UniProt
Manually annotated by BRENDA team
gene gshA or slr0990
UniProt
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
-
Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
in eukaryotes gamma -glutamylcysteine synthetase and glutathione synthetase, EC 6.3.2.3, activities are encoded by two distinct enzymes In some prokaryotes, such as Escherichia coli and Vibrio cholerae, separate enzymes exist for these two reactions. However, in some prokaryotes, such as Streptococcus agalactiae, Pasteurella multicoda and Listeria monocytogenes, both of these activities are encoded by a single bifunctional enzyme, GshF. Evolution of gamma-GCS has occurred by convergent evolution in three different lineages with no significant sequence similarities between the lineages, the Escherichia coli enzyme belongs to lineage I
evolution
P74515
Synechocystis GCL is part of the plant-like GCL family, the Synechocystis enzyme lacks the redox regulation associated with the plant enzymes and functions as a monomeric protein, indicating that evolution of redox regulation occurs later in the green lineage
malfunction
-
erythrocytes from gclm-/- mice show greatly reduced intracellular glutathione. Prolonged incubation results in complete lysis of gclm-/- erythrocytes, which can be reversed by exogenous delivery of the antioxidant Trolox. Phenylhydrazine-induced oxidative stress in glcm-/- causes dramatically increased hemolysis, markedly larger accumulations of injured erythrocytes in the spleen, erythrocyte-derived pigment hemosiderin in kidney tubules, and diminished kidney function compared to wild-type mice, phenotype, overview. Regulatory subunit GCLM-deficient erythrocytes are more prone to Ca2+-dependent suicidal cell death ex vivo. Without additional oxidative stress, the mutant animals are able to survive by slightly ramping up their generation of new erythrocytes
malfunction
-
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
metabolism
-
the regulation of GCL, especially the catalytic subunit, with stress may be compromised in aging muscles. In aging muscles with 14 days of hind-limb unloading, failure to maintain the accelerated GCL catalytic subunit production and GCL activity, are associated with the GSH depletion
metabolism
-
biosynthesis of GSH occurs by two sequential ATP-dependent enzymatic steps. The first enzyme, gamma -glutamylcysteine synthetase ligates glutamate and cysteine to yield gamma -glutamylcysteine. Glutathione synthetase, EC 6.3.2.3, the second enzyme, then catalyses the addition of glycine to yield glutathione
physiological function
-
generation of GSH1 null mutants in Leishmania infantum. Removal of even a single wild-type allelic copy of GSH1 invariably leads to the generation of an extra copy of GSH1, maintaining two intact wild-type alleles. By first supplementing the parasites with a rescue plasmid, both a single and null chromosomal GSH1 mutant can be obtained. Parasites with one intact GSH1 chromosomal allele lose the rescuing plasmid but not the double knockout, when grown in the absence of antibiotic, indicating the essentiality of the GSH1 gene. Heterozygous mutants with one allele inactivated transcribe less GSH1 mRNA and synthesize less glutathione and trypanothione. These mutants are more susceptible to oxidative stresses in vitro as promastigotes and show decreased survival inside activated macrophages producing reactive oxygen or nitrogen species. These mutants show a significant decreased survival in the presence of antimony
physiological function
D4GZN2
in a strain lacking GshA activity, diamide, a thiol-specific oxidant, significantly inhibits the growth of cells in comparison to those of the wild type. In contrast, 1.0 mM paraquat, 0.1 mM t-butyl hydroperoxide, 0.5 mM hydrogen peroxide, and 0.01 mM menadione have a much less pronounced effect on growth
physiological function
P19468
knockdown of gamma-glutamylcysteine synthetase heavy chain subunit by an adenovirus vector with short hairpin RNA against GCSh. Three days infection of GCSh-shRNA and CYP3A4 simultaneously with H4IIE cells decreases the intracellular GSH level by 50-60% without affecting the expression level of CYP3A4. Using this cell-based system sensitive to the cytotoxicity of reactive metabolites, drugs known for their hepatotoxicity are evaluated. Troglitazone, flutamide, and acetaminophen cause significant decreases of cell viability in CYP3A4/GCSh-shRNA group compared to the other groups such as GFP, CYP3A4, GFP/GCSh-shRNA, indicating that reactive metabolites produced by CYP3A4 and subsequently conjugated by GSH are involved in the cytotoxicity
physiological function
-
mice lacking the glutamate-cysteine ligase modifier subunit show an increase in myocardial ischaemia-reperfusion injury and apoptosis in ischaemic myocardium. A decrease in mitochondrial glutathione levels in ischaemic myocardium is more pronounced in mice lacking the glutamate-cysteine ligase modifier subunit than in control. The ESR signal intensity of the dimethyl-1-pyrroline-N-oxide-hydroxyl radical adducts in ischaemic myocardium is higher in mice lacking the glutamate-cysteine ligase modifier subunit than in control. Hypoxia-reoxygenation induces greater mitochondrial damage in cultured cardiomyocytes from mice lacking the glutamate-cysteine ligase modifier subunit
physiological function
-
model to explain adenosine triphosphate depletion during cystinosis. In the absence of cysteine, enzyme gamma-glutamyl cysteine synthetase forms 5-oxoproline, and the 5-oxoproline is converted into glutamate by the ATP-dependant enzyme, 5-oxoprolinase. Thus, in cysteine-limiting conditions, glutamate is cycled back into glutamate via 5-oxoproline at the cost of two ATP molecules without production of glutathione and this is the cause of the decreased levels of glutathione synthesis, as well as the ATP depletion observed in these cells. The model is also compatible with the differences seen in the human patients and the mouse model of cystinosis, where renal failure is not observed
physiological function
-
the high resistance of MYCN-amplified neuroblastoma cells against oxidative damage can be accounted for by their greater expression of both the mRNA and protein of the catalytic subunit of glutamate-cysteine ligase, the rate-limiting step in GSH biosynthesis. 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. GCL catalytic subunit knock-down enhances the vulnerability of MYCN-amplified cells to oxidative damage
physiological function
-
transfection of COV-434 granulosa tumour cell with vectors designed for the constitutive expression of Gcl catalytic subunit, Gcl modifier subunit, or both Gcl catalytic subunit and Gcl modifier subunit. GCL protein and enzymatic activity and total GSH levels are significantly increased in the GCL subunit-transfected cells. GCL-transfected cells are resistant to cell killing by treatment with hydrogen peroxide compared to control cells. In all the GCL subunit-transfected cell lines cell viability declines less than in control 1-8 h after 0.5 mM hydrogen peroxide treatment. In cells irradiated with 0, 1 or 5 Gy of g-rays, there is a dose-dependent increase in reactive oxygen species within 30 min in all cell lines, this effect is significantly attenuated in Gcl-transfected cells. Apoptosis is significantly decreased in irradiated Gclc-transfected cells compared to irradiated control cells
physiological function
-
fibroblast growth factor 9 upregulates gamma-GCS and HO-1 expression to protect cortical and dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced oxidative insult. Inhibition of gamma-GCS or HO-1 prevents the inhibitory effect of fibroblast growth factor 9 on 1-methyl-4-phenylpyridinium-induced H2O2 production and death in mesencephalic dopaminergic and cortical neurons. In the absence of 1-methyl-4-phenylpyridinium, the fibroblast growth factor 9-induced H2O2 reduction is blocked by HO-1 inhibitors, but not by gamma-GCS inhibitors
physiological function
-
expression of both glutamate-cysteine ligase catalytic and modifier subunit is mediated by the GCN2/ATF4 stress response pathway. Regulation of modifier subunit GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent
physiological function
-
gamma-GCS is rate-limiting catalyzing the regulated step of GSH biosynthesis, being both transcriptionally and post-translationally regulated, post-translational regulation of the gamma-GCS enzyme by the redox environment
physiological function
P74515
glutathione biosynthesis catalysed by glutamate-cysteine ligase and glutathione synthetase, EC 6.3.2.3, is essential for maintaining redox homoeostasis and protection against oxidative damage in diverse eukaroytes and bacteria
physiological function
-
the enzyme is rate-limiting for glutathione synthesis
physiological function
Rattus norvegicus Sprague-Dawley
-
expression of both glutamate-cysteine ligase catalytic and modifier subunit is mediated by the GCN2/ATF4 stress response pathway. Regulation of modifier subunit GCLM expression may be mediated by changes in the abundance of mRNA stabilizing or destabilizing proteins. Upregulation of GCLM levels in response to low cysteine levels may serve to protect the cell in the face of a future stress requiring GSH as an antioxidant or conjugating/detoxifying agent
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + alpha-ethyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-ethyl-L-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P0A6W9
-
-
ir
ATP + alpha-methyl-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-methyl-DL-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + alpha-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-methyl-L-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P0A6W9
-
-
ir
ATP + alpha-methylglutamate + L-Cys
ADP + phosphate + alpha-methylglutamyl-L-Cys
show the reaction diagram
-
i.e. 2-amino-2-methylpentanedioate
-
-
-
ATP + beta-aminoglutarate + L-Cys
ADP + phosphate + beta-aminoglutaryl-L-Cys
show the reaction diagram
-
i.e. 3-aminopentanedioate
-
-
-
ATP + beta-Glu + L-Cys
ADP + phosphate + beta-Glu-L-Cys
show the reaction diagram
-
17.6% of the activity relative to L-Glu
-
-
-
ATP + beta-glutamate + L-alpha-aminobutyrate
ADP + phosphate + beta-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + beta-methyl-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + beta-methyl-DL-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + beta-methylglutamate + L-Cys
ADP + phosphate + beta-methylglutamyl-L-Cys
show the reaction diagram
-
i.e. 2-amino-3-methylpentanedioate
-
-
-
ATP + D-Glu + L-2-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
show the reaction diagram
P48506
-
-
-
?
ATP + D-Glu + L-2-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
-
?
ATP + D-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
show the reaction diagram
P0A6W9
-
-
ir
ATP + D-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + D-Glu + L-Cys
ADP + phosphate + D-Glu-L-Cys
show the reaction diagram
-
-
-
-
ATP + D-Glu + L-Cys
ADP + phosphate + D-Glu-L-Cys
show the reaction diagram
-
8.5% of the activity relative to L-Glu
-
-
-
ATP + DL-alpha-aminoadipate + L-cysteine
ADP + phosphate + DL-aminoadipyl-L-cysteine
show the reaction diagram
-
about 10% of the activity with L-glutamate
-
-
?
ATP + DL-alpha-aminomethylglutarate + L-alpha-aminobutyrate
ADP + phosphate + DL-alpha-aminomethylglutaryl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + DL-alpha-aminomethylsuccinate + L-alpha-aminobutyrate
ADP + phosphate + DL-alpha-aminomethylsuccinyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + DL-beta-aminoadipate + L-alpha-aminobutyrate
ADP + phosphate + DL-beta-aminoadipyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
random ter-reactant mechanism with a preferred binding order
-
-
?
ATP + L-Glu
ADP + phosphate + 5-oxoproline
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + (R)-beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-(R)-beta-amino-iso-butyrate
show the reaction diagram
-
2fold less reactive as the S-isomer
-
ir
ATP + L-Glu + (S)-beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-(S)-beta-amino-iso-butyrate
show the reaction diagram
-
2fold as reactive as the R-isomer
-
ir
ATP + L-Glu + allo-L-threonine
ADP + phosphate + gamma-L-Glu-allo-L-threonine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-beta-amino-iso-butyrate
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + beta-chloro-L-Ala
ADP + phosphate + gamma-L-Glu-L-beta-chloro-L-Ala
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + beta-chloro-L-Ala
ADP + phosphate + gamma-L-Glu-L-beta-chloro-L-Ala
show the reaction diagram
-
reaction sequence: L-Glu binding, ATP binding, ADP release, L-beta-chloroalanine binding, phosphate release, dipeptide release
-
-
-
ATP + L-Glu + beta-chloro-L-Ala
ADP + phosphate + gamma-L-Glu-L-beta-chloro-L-Ala
show the reaction diagram
-
strain KM: 79% of the activity relative to L-Cys, strain W: 99% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + beta-chloro-L-alanine
ADP + phosphate + gamma-L-Glu-beta-chloro-L-alanine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + beta-chloro-L-alanine
ADP + phosphate + gamma-L-Glu-beta-chloro-L-alanine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + beta-cyano-L-alanine
ADP + phosphate + gamma-L-Glu-beta-cyano-L-alanine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + butylamine
ADP + phosphate + N-butyl-L-glutamine
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + D-Cys
ADP + phosphate + gamma-L-Glu-D-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + DL-allylglycine
ADP + phosphate + gamma-L-Glu-DL-allylglycine
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + DL-allylglycine
ADP + phosphate + gamma-L-Glu-DL-allylglycine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + DL-beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-DL-beta-amino-iso-butyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + ethylamine
ADP + phosphate + N-ethyl-L-glutamine
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + gamma-aminobutyrate
ADP + phosphate + gamma-L-Glu-gamma-aminobutyrate
show the reaction diagram
-
mutant R366A
-
r
ATP + L-Glu + gamma-aminobutyrate
ADP + phosphate + L-Glu-gamma-aminobutyrate
show the reaction diagram
-
-
-
ir
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
show the reaction diagram
-
14.5% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
show the reaction diagram
Escherichia coli JM109
P0A6W9
-
-
ir
ATP + L-Glu + hydroxylamine
ADP + phosphate + gamma-L-Glu-hydroxylamine
show the reaction diagram
-
slow reaction rate
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
P0A6W9
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
strain KM: 85% of the activity relative to L-Cys, strain W: 81% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
-
60% of the activity relative to L-Cys
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
show the reaction diagram
Escherichia coli S-96, Escherichia coli Crooks, Escherichia coli K-10, Escherichia coli FKU-8, Escherichia coli FKU-3, Escherichia coli FKU-1
-
-
-
-
-
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + gamma-L-Glu-2-aminobutyrate
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Ala
ADP + phosphate + gamma-L-Glu-L-Ala
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Ala
ADP + phosphate + gamma-L-Glu-L-Ala
show the reaction diagram
-
10.9% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-alanine
ADP + phosphate + gamma-L-Glu-L-alanine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-alanine
ADP + phosphate + gamma-L-Glu-L-alanine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
r
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
show the reaction diagram
P48506, P48507
-
-
ir
ATP + L-Glu + L-alpha-aminoheptanoate
ADP + phosphate + gamma-L-Glu-L-alpha-aminoheptanoate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-C-allylglycine
ADP + phosphate + gamma-L-Glu-L-C-allylglycine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Proteus vulgaris, Bacterium cadaveris, Pseudomonas schuylkilliensis
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P32477
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q26820
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P46309
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q56277
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P90557
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P97494, Q97SC0
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q09768
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q9NFN6
-
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P48506, P48507
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
combines glutamate and cysteine through the gamma carboxylmoiety rather than the alpha carboxyl moiety found in protein amide bonds, imparting resistance to proteolytic degradation
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
reaction can be performed by the catalytic subunit alone, but presence of the regulatory subunit in the holoenzyme increases the activity
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
catalyzes the biosynthesis of the GSH precursor
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate limiting step in GSH biosynthesis, rare hereditary enzyme deficiency is associated with low erythrocyte levels of the enzyme leading to hemolytic anemia
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate limiting step in GSH de novo biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in glutathione biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in the biosynthesis of glutathione
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q9NFN6
first and rate-limiting step in the glutathione biosynthesis, important for maintenance of the intracellular thiol redox status and in detoxification processes
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P0A6W9
first and rate-limiting step in the GSH biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first step in the biosynthesis of trypanothione via GSH
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first step in the de novo biosynthesis of the tripeptide glutathione
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
part of GSH biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate limiting and first step in glutathione biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P32477
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P0A6W9
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q26820
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P46309
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q56277
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P90557
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q09768
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P19468, P48508
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P97494, Q97SC0
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P48506, P48507
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting enzyme in the GSH biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis, regulation mechanism and model
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step of the chemoprotective glutathione synthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
regulation and signaling in GSH de novo synthesis pathway
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
the enzyme has key influence on glutathione homeostasis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
the enzyme is involved in the biosynthesis of GSH, which is used for detoxification of herbicides by the plant
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Escherichia coli S-96
-
-
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Escherichia coli JM109
P0A6W9
first and rate-limiting step in the GSH biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Escherichia coli Crooks, Escherichia coli K-10, Escherichia coli FKU-8, Escherichia coli FKU-3, Escherichia coli FKU-1
-
-
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
key regulatory enzyme in glutathione biosynthesis
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
enzyme catalyzes the first committed step in the biosynthesis of trypanothione, i.e. diglutathionylspermidine
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
glutathione biosynthesis
-
-
-
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
show the reaction diagram
-
13.7% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-homoserine
ADP + phosphate + gamma-L-Glu-L-homoserine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-homoserine
ADP + phosphate + gamma-L-Glu-L-homoserine
show the reaction diagram
-
17% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-isoleucine
ADP + phosphate + gamma-L-Glu-L-isoleucine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-leucine
ADP + phosphate + gamma-L-Glu-L-leucine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-norleucine
ADP + phosphate + gamma-L-Glu-L-norleucine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-norleucine
ADP + phosphate + gamma-L-Glu-L-norleucine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
show the reaction diagram
-
14% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
show the reaction diagram
Escherichia coli JM109
P0A6W9
-
-
ir
ATP + L-Glu + L-Ser
ADP + phosphate + gamma-L-Glu-L-Ser
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Ser
ADP + phosphate + gamma-L-Glu-L-Ser
show the reaction diagram
-
14.5% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-Ser
ADP + phosphate + gamma-L-Glu-L-Ser
show the reaction diagram
-
strain KM: 18% of the activity relative to L-Cys, strain W: 13% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-Ser
ADP + phosphate + gamma-L-Glu-L-Ser
show the reaction diagram
Escherichia coli S-96, Escherichia coli Crooks, Escherichia coli K-10, Escherichia coli FKU-8, Escherichia coli FKU-3, Escherichia coli FKU-1
-
-
-
-
-
ATP + L-Glu + L-serine
ADP + phosphate + gamma-L-Glu-L-serine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-serine
ADP + phosphate + gamma-L-Glu-L-serine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-Thr
ADP + phosphate + gamma-L-Glu-L-Thr
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-threonine
ADP + phosphate + gamma-L-Glu-L-threonine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + L-threonine
ADP + phosphate + gamma-L-Glu-L-threonine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-Glu + L-threonine
ADP + phosphate + gamma-L-Glu-L-threonine
show the reaction diagram
-
allo-L-threonine is a 5fold better substrate than L-threonine
-
ir
ATP + L-Glu + L-valine
ADP + phosphate + gamma-L-Glu-L-valine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + methylamine
ADP + phosphate + N-methyl-L-glutamine
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + n-propylamine
ADP + phosphate + N-propyl-L-glutamine
show the reaction diagram
-
-
-
-
?
ATP + L-Glu + O-methyl-DL-serine
ADP + phosphate + gamma-L-Glu-O-methyl-DL-serine
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + S-methyl-L-Cys
ADP + phosphate + gamma-L-Glu-S-methyl-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + S-methyl-L-Cys
ADP + phosphate + gamma-L-Glu-S-methyl-L-Cys
show the reaction diagram
-
strain KM: 70% of the activity relative to L-Cys, strain W: 70% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + S-methyl-L-Cys
ADP + phosphate + gamma-L-Glu-L-S-methyl-Cys
show the reaction diagram
P0A6W9
-
-
ir
ATP + L-Glu + S-methyl-L-cysteine
ADP + phosphate + gamma-L-Glu-S-methyl-L-cysteine
show the reaction diagram
P19468, P48508
-
-
ir
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P48506
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P19468
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q8W4W3
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q1W2L8
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P97494
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q9W3K5
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
B4YE15
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
B2ZG39
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P74515
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
B2ZG39
rate-limiting step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
first step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q8W4W3
chilling stress strongly induces gamm-ECS mRNA
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
first step of glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P19468
gonadotropins regulate expression of follicular glutamate cysteine ligase in a follicle stage-dependent manner and in a glutamate cysteine ligase subunit-dependent manner
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione biosynthesis, plays a central role in glutathione homeostasis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P48506
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in GSH synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in GSH synthesis. Overexpression of the catalytic and modifier subunits of the enzyme leads to enhanced GCL activity and resistance to TNF-induced apoptosis. Maintenance of mitochondrial integrity is a major mechanism of protection against TNF-induced apoptosis in Hepa-1 cells overexpressing the enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
overexpression of gamma-GCS decreases drug-induced oxidative stress and confers drug resistance
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in the glutathione biosynthesis pathway
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
O23736
rate-limiting step in the biosynthesis of GSH. The regulatory mechanism is based on two intramolecular redox-sensitive disulfide bonds. Reduction of one disulfide bond allows a beta-hairpin motif to shield the active site of Brassica juncea GCL, thereby preventing the access of substrates. Reduction of the second disulfide bond reversibly controls dimer to monomer transition of the glutamate-cysteine ligase that is associated with a significant inactivation of the enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
reaction is catalyzed by the bifunctional enzyme gamma-glutamylcysteine synthetase-glutathione synthetase
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
the enzyme plays a role in disease resistance in Arabidopsis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P97494
the mechanism of modulation of eukaryotic gamma-glutamylcysteine ligase enzymes may include specific binding of ligands such as pyridine dinucleotide phosphates and reversible protein phosphorylation
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
the thiol-based regulation of glutamate-cysteine ligase provides a posttranslational mechanism for modulating enzyme activity in response to in vivo redox environment
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
treatment of human breast cancer cells with 2-deoxy-D-glucose causes metabolic oxidative stress that is accompanied by increases in steady-state levels of glutamate cysteine ligase mRNA, glutamate cysteine ligase activity and glutathione content
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
upregulation of gamma-glutamate-cysteine ligase is part of the long-term adaptation process to iron accumulation in neuronal SH-SY5Y cells
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
evidence of TNF-alpha-mediated LEDGF induction of gamma-glutamylcysteine synthetase heavy subunit and mRNA expression. TNF-alpha-induced intracellular level of reactive oxygen species is critical for the regulation of the multidomain adaptor protein LEDGF, which subsequently influences cellular glutathione content by regulating transcription of gamma-glutamylcysteine synthetase heavy subunit
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
thyroid hormone promotes glutathione synthesis in astrocytes by upregulation of glutamate cysteine ligase through differential stimulation of its catalytic and modulator subunit mRNAs
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
B4YE15
first step in the biosynthesis of glutathione, pathway overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
GCL is the key glutathione-synthesizing enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
GCL is the rate-limiting enzyme in glutathione biosynthesis, its catalytic subunit GCLC determines this de novo synthesis. Induction of GCLC is a strategy to enhance the antioxidant capability in cells
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
mechanisms in regulation of GCLC and GCLM expression, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione synthesis, a mutation in the catalytic subunit gene 5'-UTR leads to reduced enzyme activity
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q1W2L8
redox regulation of the enzyme, a redox switch based on CC2-mediated homodimerization is unique to plant GCL enzymes, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
redox regulation of the enzyme, a redox switch based on CC2-mediated homodimerization is unique to plant GCL enzymes, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
redox regulation of the enzyme, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
the enzyme acts endogenously as an antioxidant and is involved in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P19468
assay at pH 8
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + ?-L-glutamyl-L-cysteine
show the reaction diagram
Mus musculus, Homo sapiens, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
-
-
-
-
?
ATP + N-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + N-methyl-L-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P0A6W9
-
-
ir
ATP + N-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + N-methyl-L-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + N-methyl-L-glutarate + L-Cys
ADP + phosphate + N-methyl-L-glutaryl-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + threo-beta-hydroxy-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + threo-beta-hydroxy-DL-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
ATP + threo-beta-hydroxy-L-Glu + L-Cys
ADP + phosphate + threo-beta-hydroxy-L-Glu-L-Cys
show the reaction diagram
-
-
-
-
-
ATP + threo-gamma-hydroxy-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + threo-gamma-hydroxy-L-glutamyl-L-alpha-aminobutyrate
show the reaction diagram
P19468, P48508
-
-
ir
glutamate + ATP + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
assay at pH 8.2
-
-
?
GTP + L-Glu + L-Cys
GDP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
87% of the activity relative to ATP
-
-
-
UTP + L-Glu + L-Cys
UDP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
12% of the activity relative to ATP
-
-
-
L-glutamate + L-cysteine + ATP
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
D7P1H2
-
-
-
?
additional information
?
-
P0A6W9
substrate specificity
-
?
additional information
?
-
P48506, P48507
substrate specificity
-
?
additional information
?
-
-
binding of ATP to the enzyme increases the binding affinity for L-Glu by 18fold, while binding of L-Glu or L-alpha-aminobutyrate decreases the affinity for binding of the other by 6fold
-
?
additional information
?
-
-
substrate specificity, beta-alanine, (R,S)-beta-amino-n-butyrate, and (R,S)-alpha-ethyl-beta-alanine are no substrates
-
?
additional information
?
-
P0A6W9
substrate specificity, poor substrates are beta-glutamate, (R,S)-beta-methyl-DL-glutamate, (R,S)-gamma-methyl-glutamate, L-aspartate, and DL-alpha-aminoadipate
-
?
additional information
?
-
P19468, P48508
the enzyme forms gamma-glutamyl-Tris in Tris buffers, substrate specificity, the L-glutamate analogues L-alpha-aminoadipate, L-asparate, glutarate, gamma-aminobutyrate, and gamma-methyl-DL-glutamate are poor substrates, beta-alanine, RS-beta-amino-n-butyrate, and RS-alpha-ethyl-beta-alanine are no substrates
-
?
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
P97494, Q97SC0
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
P48506, P48507
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, enzyme overexpression provides resistance to melphalan and other drugs, overview, protection of cancer cells by increased GSH levels
-
?
additional information
?
-
P19468, P48508
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
-
Met4 regulates the GSH1 expression in response to GSH availability, model for genetic regulation and control of GSH biosynthesis
-
?
additional information
?
-
Q26820
most of the GSH produced in this pathway is converted to trypanothione
-
?
additional information
?
-
-
overexpression of cytochrome P450 2E1 in human hepatocarcinoma cell line HepG2 increases the intracellular H2O2 level by 40-50% and therefore results in a 2fold increase in enzyme expression
-
?
additional information
?
-
-
the genotype of GLCLC is associated with drug sensitivity or resistance, respectively
-
?
additional information
?
-
-
differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation
-
-
-
additional information
?
-
-
rate-limiting enzyme in GSH biosynthesis
-
-
-
additional information
?
-
-
enhancement of the glutathione biosynthetic capability, particularly in neuronal tissues, can extend the life span of flies
-
-
-
additional information
?
-
-
ARE-driven gene expression of Gclc via a MEK/Nrf2 pathway can help to protect macrophages from oxidative stress due to hyperhomocysteinemia
-
-
-
additional information
?
-
-
GCL activity is not associated with susceptibility to chronic obstructive pulmonary disease patients or disease severity, overview
-
-
-
additional information
?
-
-
GCLC polymorphisms are associated with lower lung function levels causing lung disease, especially in association with oxidative stress due to smoking
-
-
-
additional information
?
-
B2ZG39
hyperthermal stress triggers adaptive increases in intracellular GSH biosynthesis in cnidarians as a protective response to oxidative/nitrosative stress, overview
-
-
-
additional information
?
-
-
induced acute edematous pancreatitis is characterized by marked glutathione depletion in the pancreas, and a rapid restoration of GSH levels involving the enzyme, overview
-
-
-
additional information
?
-
-
insulin stimulation of GCL catalytic subunit expression increases endothelial GSH during oxidative stress, overview. Functional importance of insulin in Nrf2-dependent transcriptional upregulation of GCLC in GSH recovery during oxidative challenge, role for Nrf2 involvement in both constitutive and inducible endothelial GCLc expression and GSH synthesis, while PI3K/Akt/mTOR signaling appears to participate only in insulin-inducible GSH synthesis. Low glucose enhances the insulin-mediated increase in GCLc expression
-
-
-
additional information
?
-
-
post-translational regulation of GCL, overview
-
-
-
additional information
?
-
-
post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview
-
-
-
additional information
?
-
-
the cis-element signaling of Nrf2/EpRE is involved in resveratrol-mediated induction of GCL genes
-
-
-
additional information
?
-
-
the modifier subunit GCLM is not correlated with methamphetamine-use disorder or schizophrenia in the Japanese population, overview
-
-
-
additional information
?
-
P19468
tumor development in gut tissue does not affect GCS enzyme activity
-
-
-
additional information
?
-
-
purified rat kidney GCL holoenzyme is capable of undergoing autophosphorylation, the phosphorylation is specific for the GCLC subunit, no phosphorylation of the GCLM subunit
-
-
-
additional information
?
-
Q1W2L8
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, CC2 plays a role in GCL redox regulation, overview
-
-
-
additional information
?
-
-
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, CC2 plays no role in GCL redox regulation, overview
-
-
-
additional information
?
-
-
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, which both strongly impact on GCL activity in vitro, cysteines of CC2 involved in the monomer-dimer transition in GCL. CC2 plays a role in GCL redox regulation, overview
-
-
-
additional information
?
-
-
enzyme is able to to combine glutamine and amines to form gamma-glutamylamides. The reaction rate depende on the length if the methylene chain of the amines in the following decreasing order: n-propylamine > butylamine > ethylamine > methylamine
-
-
-
additional information
?
-
Escherichia coli JM109
P0A6W9
substrate specificity, poor substrates are beta-glutamate, (R,S)-beta-methyl-DL-glutamate, (R,S)-gamma-methyl-glutamate, L-aspartate, and DL-alpha-aminoadipate
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
catalyzes the biosynthesis of the GSH precursor
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate limiting step in GSH biosynthesis, rare hereditary enzyme deficiency is associated with low erythrocyte levels of the enzyme leading to hemolytic anemia
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate limiting step in GSH de novo biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in glutathione biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first and rate-limiting step in the biosynthesis of glutathione
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q9NFN6
first and rate-limiting step in the glutathione biosynthesis, important for maintenance of the intracellular thiol redox status and in detoxification processes
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P0A6W9
first and rate-limiting step in the GSH biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first step in the biosynthesis of trypanothione via GSH
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
first step in the de novo biosynthesis of the tripeptide glutathione
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
part of GSH biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate limiting and first step in glutathione biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P32477
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P0A6W9
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q26820
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P46309
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q56277
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P90557
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Q09768
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P19468, P48508
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P97494, Q97SC0
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
P48506, P48507
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting enzyme in the GSH biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis, regulation mechanism and model
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
rate-limiting step of the chemoprotective glutathione synthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
regulation and signaling in GSH de novo synthesis pathway
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
the enzyme has key influence on glutathione homeostasis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
-
the enzyme is involved in the biosynthesis of GSH, which is used for detoxification of herbicides by the plant
-
?
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
-
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
rate-limiting step in glutathione biosynthesis
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
key regulatory enzyme in glutathione biosynthesis
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
enzyme catalyzes the first committed step in the biosynthesis of trypanothione, i.e. diglutathionylspermidine
-
-
-
ATP + L-Glu + L-Cys
?
show the reaction diagram
-
glutathione biosynthesis
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
show the reaction diagram
Escherichia coli JM109
P0A6W9
first and rate-limiting step in the GSH biosynthesis
-
ir
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P19468
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P74515
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
B2ZG39
rate-limiting step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
first step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q8W4W3
chilling stress strongly induces gamm-ECS mRNA
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
first step of glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P19468
gonadotropins regulate expression of follicular glutamate cysteine ligase in a follicle stage-dependent manner and in a glutamate cysteine ligase subunit-dependent manner
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione biosynthesis, plays a central role in glutathione homeostasis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P48506
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in GSH synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in GSH synthesis. Overexpression of the catalytic and modifier subunits of the enzyme leads to enhanced GCL activity and resistance to TNF-induced apoptosis. Maintenance of mitochondrial integrity is a major mechanism of protection against TNF-induced apoptosis in Hepa-1 cells overexpressing the enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
overexpression of gamma-GCS decreases drug-induced oxidative stress and confers drug resistance
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in the glutathione biosynthesis pathway
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
O23736
rate-limiting step in the biosynthesis of GSH. The regulatory mechanism is based on two intramolecular redox-sensitive disulfide bonds. Reduction of one disulfide bond allows a beta-hairpin motif to shield the active site of Brassica juncea GCL, thereby preventing the access of substrates. Reduction of the second disulfide bond reversibly controls dimer to monomer transition of the glutamate-cysteine ligase that is associated with a significant inactivation of the enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
reaction is catalyzed by the bifunctional enzyme gamma-glutamylcysteine synthetase-glutathione synthetase
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
the enzyme plays a role in disease resistance in Arabidopsis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
P97494
the mechanism of modulation of eukaryotic gamma-glutamylcysteine ligase enzymes may include specific binding of ligands such as pyridine dinucleotide phosphates and reversible protein phosphorylation
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
the thiol-based regulation of glutamate-cysteine ligase provides a posttranslational mechanism for modulating enzyme activity in response to in vivo redox environment
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
treatment of human breast cancer cells with 2-deoxy-D-glucose causes metabolic oxidative stress that is accompanied by increases in steady-state levels of glutamate cysteine ligase mRNA, glutamate cysteine ligase activity and glutathione content
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
upregulation of gamma-glutamate-cysteine ligase is part of the long-term adaptation process to iron accumulation in neuronal SH-SY5Y cells
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
first rate-limiting step in GSH biosynthesis, GCL is a major determinant of cellular GSH levels, pathway overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
B4YE15
first step in the biosynthesis of glutathione, pathway overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
GCL is the key glutathione-synthesizing enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
GCL is the rate-limiting enzyme in glutathione biosynthesis, its catalytic subunit GCLC determines this de novo synthesis. Induction of GCLC is a strategy to enhance the antioxidant capability in cells
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
mechanisms in regulation of GCLC and GCLM expression, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
rate-limiting enzyme in glutathione synthesis, a mutation in the catalytic subunit gene 5'-UTR leads to reduced enzyme activity
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
Q1W2L8
redox regulation of the enzyme, a redox switch based on CC2-mediated homodimerization is unique to plant GCL enzymes, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
redox regulation of the enzyme, a redox switch based on CC2-mediated homodimerization is unique to plant GCL enzymes, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
redox regulation of the enzyme, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
show the reaction diagram
-
the enzyme acts endogenously as an antioxidant and is involved in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + ?-L-glutamyl-L-cysteine
show the reaction diagram
Mus musculus, Homo sapiens, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
-
-
-
-
?
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
P97494, Q97SC0
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
P48506, P48507
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, enzyme overexpression provides resistance to melphalan and other drugs, overview, protection of cancer cells by increased GSH levels
-
?
additional information
?
-
P19468, P48508
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
-
Met4 regulates the GSH1 expression in response to GSH availability, model for genetic regulation and control of GSH biosynthesis
-
?
additional information
?
-
Q26820
most of the GSH produced in this pathway is converted to trypanothione
-
?
additional information
?
-
-
overexpression of cytochrome P450 2E1 in human hepatocarcinoma cell line HepG2 increases the intracellular H2O2 level by 40-50% and therefore results in a 2fold increase in enzyme expression
-
?
additional information
?
-
-
the genotype of GLCLC is associated with drug sensitivity or resistance, respectively
-
?
additional information
?
-
-
differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation
-
-
-
additional information
?
-
-
rate-limiting enzyme in GSH biosynthesis
-
-
-
additional information
?
-
-
ARE-driven gene expression of Gclc via a MEK/Nrf2 pathway can help to protect macrophages from oxidative stress due to hyperhomocysteinemia
-
-
-
additional information
?
-
-
GCL activity is not associated with susceptibility to chronic obstructive pulmonary disease patients or disease severity, overview
-
-
-
additional information
?
-
-
GCLC polymorphisms are associated with lower lung function levels causing lung disease, especially in association with oxidative stress due to smoking
-
-
-
additional information
?
-
B2ZG39
hyperthermal stress triggers adaptive increases in intracellular GSH biosynthesis in cnidarians as a protective response to oxidative/nitrosative stress, overview
-
-
-
additional information
?
-
-
induced acute edematous pancreatitis is characterized by marked glutathione depletion in the pancreas, and a rapid restoration of GSH levels involving the enzyme, overview
-
-
-
additional information
?
-
-
insulin stimulation of GCL catalytic subunit expression increases endothelial GSH during oxidative stress, overview. Functional importance of insulin in Nrf2-dependent transcriptional upregulation of GCLC in GSH recovery during oxidative challenge, role for Nrf2 involvement in both constitutive and inducible endothelial GCLc expression and GSH synthesis, while PI3K/Akt/mTOR signaling appears to participate only in insulin-inducible GSH synthesis. Low glucose enhances the insulin-mediated increase in GCLc expression
-
-
-
additional information
?
-
-
post-translational regulation of GCL, overview
-
-
-
additional information
?
-
-
post-translational regulation of GCL, overview. GCLC and GCLM polymorphisms increase disease susceptibility in humans, overview
-
-
-
additional information
?
-
-
the cis-element signaling of Nrf2/EpRE is involved in resveratrol-mediated induction of GCL genes
-
-
-
additional information
?
-
-
the modifier subunit GCLM is not correlated with methamphetamine-use disorder or schizophrenia in the Japanese population, overview
-
-
-
additional information
?
-
P19468
tumor development in gut tissue does not affect GCS enzyme activity
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate
ATP
P48506, P48507
the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate
ATP
P97494, Q97SC0
the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate
ATP
-
the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate
ATP
P19468, P48508
the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate
ATP
-
the gamma-phosphate is located close to the glutamate binding site by the glycine-rich P-loop, built by the motif M(A/G)FGMGXXCLQ, to facilitate the formation of the enzyme-bound reaction intermediate gamma-glutamyl-phosphate
ATP
Q26820
-
ATP
-
dependent on
ATP
-
dependent on
ATP
-
required as MgATP2-
ATP
-
; binding of L-Glu to the enzyme increases the binding affinity for ATP by 18fold
ATP
-
associated with Mg2+ binding at the second n2 metal binding site
ATP
-
dependent on
ATP
B2ZG39
-
ATP
B4YE15
-
ATP
P74515
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
As3+
-
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 occurrs independent of the Nrf1/2 transcription factors
Cu2+
-
induces expression of heavy subunit
Cu2+
P0A6W9
2 divalent metal ions per enzyme molecule are bound, can be replaced by Mn2+ and Mg2+, binding mechanism and kinetics, overview
K+
-
absolute requirement for Mg2+, Mn2+, and K+ ions
Mg2+
-
divalent metal ion required, especially Mg2+, optimal concentration depending on ATP concentration
Mg2+
-
inactive in absence of Mg2+, maximal activity at 10 mM
Mg2+
-
absolute requirement, maximal activity at 30-50 mM
Mg2+
P48506, P48507
required, bound to the erythrocyte enzyme
Mg2+
P19468, P48508
required, bound to the kidney enzyme, involved in enzyme phosphorylation, can be substituted by Mn2+ by 25%; required, bound to the kidney enzyme, involved in enzyme phosphorylation, can be substituted by Mn2+ by only 25%
Mg2+
-
Mg2+ or Mn2+ are required
Mg2+
-
required as MgATP2-
Mg2+
-
required, bound as MgATP2-, the metal ion specificity is determined by the second binding site n2 which also is involved in ATP binding, located in the active site and formed by 3 conserved residues Glu53, Gln321, and Glu489, Mg2+ can partly be substituted by Mn2+
Mg2+
P0A6W9
2 divalent metal ions per enzyme molecule are bound, Mg2+ sharpens the substrate specificity, increases the resistance to L-buthionine-S,R-sulfoximine, can be replaced by Mn2+ and Cu2+, binding mechanism and kinetics, overview
Mg2+
B2ZG39
-
Mg2+
B4YE15
-
Mg2+
-
required
Mg2+
-
required
Mg2+
-
required
Mg2+
Q1W2L8
-
Mg2+
-
absolute requirement for Mg2+, Mn2+, and K+ ions
Mg2+
-
required
Mg2+
P74515
required
Mn2+
-
can replace Mg2+ with 18% of the efficiency
Mn2+
P48506, P48507
bound to the erythrocyte enzyme
Mn2+
P19468, P48508
bound to the kidney enzyme, can substitute for Mg2+ by 25%; bound to the kidney enzyme, can substitute for Mg2+ by only 25%
Mn2+
-
Mg2+ or Mn2+ are required
Mn2+
-
can partly substitute for Mg2+
Mn2+
P0A6W9
2 divalent metal ions per enzyme molecule are bound, Mg2+ broadens the substrate specificity, decreases the resistance to L-buthionine-S,R-sulfoximine, can be replaced by Mg2+ and Cu2+, binding mechanism and kinetics, overview
Sodium arsenite
-
induces expression of heavy subunit
Zn2+
-
induces expression of heavy subunit
Mn2+
-
absolute requirement for Mg2+, Mn2+, and K+ ions
additional information
-
the first metal binding site n1 binds free metal ions and is composed of 3 conserved residues Glu55, Glu93, and Glu100, n1 also is involved in positioning of L-glutamate for the reaction, located in the active site
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-amino-4-[(2R,S)-2-carboxy-3-hydroxypropyl-(R,S)-sulfonimidoyl]butanoic acid
-
; slow-binding, irreversible inactivation, ATP-dependent, a N-phosphorylated reaction intermediate is tightly bound to the enzyme, mechanism-based
(2S)-2-amino-4-[(2R,S)-2-carboxy-3-phenylpropyl-(R,S)-sulfonimidoyl]butanoic acid
-
; weak, reversible inhibition
(2S)-2-amino-4-[(2R,S)-2-carboxybutyl-(R,S)-sulfonimidoyl]butanoic acid
-
; slow-binding, irreversible inactivation, ATP-dependent, a N-phosphorylated reaction intermediate is tightly bound to the enzyme, mechanism-based
(2S)-2-amino-4-[(2R,S)-2-carboxyhexyl-(R,S)-sulfonimidoyl]butanoic acid
-
; slow-binding, irreversible inactivation, ATP-dependent, a N-phosphorylated reaction intermediate is tightly bound to the enzyme, mechanism-based
(2S)-2-amino-4-[(2R,S)-2-carboxyoctyl-(R,S)-sulfonimidoyl]butanoic acid
-
; weak, reversible inhibition
(2S)-2-amino-4-[(2R,S)-2-carboxypropyl-(R,S)-sulfonimidoyl]butanoic acid
-
; slow-binding, irreversible inactivation, ATP-dependent, a N-phosphorylated reaction intermediate is tightly bound to the enzyme, mechanism-based
(2S)-2-amino-4-[2-carboxyethyl-(R,S)-sulfonimidoyl]butanoic acid
-
; slow-binding, irreversible inactivation, ATP-dependent, a N-phosphorylated reaction intermediate is tightly bound to the enzyme, mechanism-based
2-mercaptoethanol
-
-
4-hydroxy-2-nonenal
-
treatment with 4-hydroxy-2-nonenal results in the dose-dependent adduction of both monomeric GCLC and GCLM. 4-Hydroxy-2-nonenal-mediated adduction of monomeric GCLC results in a dose-dependent increase in GCLC enzymatic activity. Treatment of GCL holoenzyme causes a dose-dependent decrease in GCL activity. 4-Hydroxy-2-nonenal-mediated inhibition of GCL holoenzyme activity is associated with a reduction in the levels of heterodimeric GCL holoenzyme complex due to increase in high molecular weight complexes. 4-Hydroxy-2-nonenal modification simultaneously activates monomeric GCLC activity and prevents its ability to heterodimerize with GCLM and form functional GCL holoenzyme
4-Methylene glutamate
-
no inhibition
4-Methylene glutamate
-
-
4-methylene-L-glutamate
P19468, P48508
; weak, competitive
5'-ADP
-
-
5'-AMP
-
-
5-Chloro-4-oxo-L-norvaline
P19468, P48508
; irreversible, binding is reduced by L-glutamate, increased by L-alpha-aminobutyrate, and is completely dependent on divalent cations
acetaminophen
-
treatment promotes the loss of glutamate cysteine ligase in liver. Activation of glycogen synthase kinase 3beta is a key mediator of the initial phase of acetaminophen-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver. The silencing of glycogen synthase kinase 3beta decreases the loss of hepatic GCL, and promotes greater GSH recovery in liver following acetaminophen treatment
Ag+
-
complete inactivation
alpha-Methyl-DL-glutamate
-
-
antimony
-
heterozygous mutants with one allele inactivated show a significant decreased survival in the presence of antimony
ATP
-
substrate inhibition of mutant R179A, when only one other substrate is saturating
beta-Methylglutamate
-
-
buthionine sulfone
P19468, P48508
-
buthionine sulfoxime
P74515
-
-
buthionine sulfoximine
-
only in presence of ATP
buthionine sulfoximine
-
-
buthionine sulfoximine
-
inhibition is about 20times more effectively than with prothionine sulfoximine, and at least 100times more effective than methionine sulfoximine
buthionine sulfoximine
-
-
buthionine sulfoximine
-
-
buthionine sulfoximine
P90557
-
buthionine sulfoximine
Q09768
-
buthionine sulfoximine
-
complete inhibition
buthionine sulfoximine
-
-
buthionine sulfoximine
Q9W3K5
-
buthionine sulfoximine
-
GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL
buthionine sulfoximine
-
specific inhibitor of GCL
buthionine sulfoximine
Q1W2L8
specific inhibitor of GCL
buthionine sulfoximine
-
specific inhibitor of GCL
carbon tetrachloride
-
a single dose of 1589 mg/kg body weight of carbon tetrachloride causes changes in CGL activity and glutathione content in multiple organs of deer mice. Hepatic GCL activity and GSH content are depleted substantially, renal GCL activity increases. Blood, brain and heart GCL activities increase, whereas GSH contents decrease significantly
Cd2+
-
0.2 mM, activity is reduced by 35%
Cd2+
-
no residual activity
Chloroacetone
P19468, P48508
-
ciprofibrate
-
inhibits expression of heavy subunit
cis-1-Amino-1,3-dicarboxycyclohexane
-
-
Co2+
-
22% residual activity
Cu2+
-
27% residual activity
cystamine
-
no inhibition
cystamine
-
-
cystamine
-
completely reversible by DTT
cystamine
-
7.5 mM MgCl2 + 7.5 mM L-Glu protect
cystamine
-
L-Glu protects, ATP enhances rate of inactivation
cystamine
-
-
cystamine
-
-
cystamine
-
-
cystamine
-
irreversible inactivation of the wild-type enzyme, loss of 75% activity within 10 min at 0.01 mM, binds to active site Cys319 and in this way blocks the binding of substrate to the enzyme, no inhibition of the mutant C319A enzyme
cystamine
Q9NFN6
irreversible
cysteamine
-
-
cysteamine
-
rapid inactivation, reversible by thiols
cysteamine
P48506, P48507
rapid inactivation, reversible by thiols
cysteamine
P97494, Q97SC0
rapid inactivation, reversible by thiols
cysteamine
-
rapid inactivation, reversible by thiols
cysteamine
P19468, P48508
rapid inactivation, reversible by thiols
cysteamine
-
rapid inactivation, reversible by thiols
cysteamine
-
inactivation of wild-type enzyme and mutant C553G after 90 min at 4C, 0.2 mM cysteamine and 2 mM ATP
cysteamine
-
wild-type enzyme is inhibited by 75% at 0.01 mM after 10 min, complete irreversible inhibition at 10 mM, the mutant C319Ais completely resistant to cysteamine
cysteamine
-
complete inhibition
D-3-Amino-1-chloro-2-pentanone
-
highly potent irreversible inactivator
D-3-Amino-1-chloro-2-pentanone
P19468, P48508
-
diquat
-
inhibits expression of heavy subunit
dithioerythritol
-
-
dithiothreitol
-
-
dithiothreitol
-
inhibition of wild-type holoenzyme and C553G mutant holoenzyme, the latter is more sensitive
DL-2-Amino-4-phosphonobutanoate
-
-
DL-alpha-Aminomethylglutarate
-
-
DL-Aminoadipate
-
weak
DTT
Q1W2L8
-
gamma-Glu-2-aminobutanoyl-Gly
-
i.e. ophthalmic acid, inhibits only slightly, but inhibits much more after treatment of the holoenzyme with DTT, the recombinant and isolated heavy subunit enzyme is substantially inhibited without DTT
gamma-glutamylcysteine
-
-
gamma-L-Glu-L-Cys
-
-
gamma-methylene-D-glutamate
P19468, P48508
-
gamma-Methylglutamate
-
-
gamma-Methylglutamate
-
D-isomer inhibits, L-isomer not, competitively towards Glu, inactivation is dependent upon the presence of Mg2+ or Mn2+, Glu protects against inactivation
glutathione
-
feed-back inhibition
glutathione
-
feed-back inhibition; GSH inhibits, GSSG has no inhibitory effect
glutathione
-
whole enzyme and large subunit inhibited
glutathione
-
-
glutathione
-
inhibited by both GSSG and GSH
glutathione
-
GSSG inhibits, GSH has no inhibitory effect
glutathione
-
feed-back inhibition
glutathione
-
-
glutathione
-
GSH
glutathione
-
-
glutathione
-
GSH
glutathione
-
feedback inhibition, non-competitive inhibitor versus both glutamate and cysteine
glutathione
-
feedback inhibition
glutathione
-
-
glutathione
-
the cataytic subunit GCLC is feddback inhibited by GSH
glutathione
-
feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate
glutathione
-
feedback inhibition
glutathione
Q1W2L8
feedback inhibition
glutathione
-
feedback inhibition
glutathione
-
feedback-regulation. The structure of the GCL-glutathione complex to 2.5 A resolution indicates that the inhibitor occupies both the glutamate- and the presumed cysteine-binding site and disrupts the previously observed Mg2+-coordination in the ATP-binding site
glutathione
-
competitive to L-Glu, non-competitive to ATP and L-Cys
glutathione
P74515
substrate inhibition
GSH
-
feedback inhibition
GSH
P0A6W9
feedback inhibition
GSH
P48506, P48507
; feedback inhibition
GSH
P97494, Q97SC0
feedback inhibition
GSH
-
feedback inhibition
GSH
P19468, P48508
feedback inhibition, competitive to L-Glu
GSH
-
feedback inhibition
GSH
Q26820
; feedback inhibition
GSH
-
noncompetitive to L-glutamate, inhibition is not dependent on reduction of disulfide bonds between the 2 subunits in the holoenzyme
GSH
-
competitive
GSH
-
feedback inhibition, mutant R127C is not sensitive
GSH
-
feedback inhibition, acts on the heavy catalytic subunit
GSH
-
; feedback inhibition, acts on the heavy catalytic subunit
GSH
-
feedback inhibition
GSH
-
reduced, feedback inhibition of wild-type and mutants
GSH
-
feedback inhibition, the elimination of disulfide bridges between the subunits renders the enzyme more sensitive to inhibition
GSH
-
regulatory function, represses expression of GSH1 gene
GSH
-
competitive feedback inhibition with respect to L-glutamate
GSH
-
noncompetitive versus L-glutamate or ATP
GSH
-
wild-type enzyme is nearly uninhibited by GSH (Ki about 140 mM), shorter gamma-glutamylcysteine synthetase domain constructs are strongly inhibited (Ki about 15 mM)
Hg2+
-
no residual activity
iodoacetamide
-
-
iodoacetamide
-
-
L-2-Amino-4-oxo-5-chloropentanoate
-
inactivation requires very low concentration, 0.003-0.006 mM, of Mg2+ or certain other divalent cations, L-Glu, but not D-Glu protects competitively against inactivation, protection is increased in the presence of ATP or ADP
L-2-Aminohexanedioate
-
i.e. L-alpha-aminoadipate
L-3-Amino-1-chloro-2-pentanone
-
highly potent irreversible inactivator
L-alpha-aminobutyrate
-
substrate inhibition of mutant R179A, when only one other substrate is saturating
L-buthionine sulfone
P19468, P48508
competitive, reversible
L-buthionine sulfoximine
-
95% inhibition at 0.001 mM
L-buthionine sulfoximine
-
-
L-buthionine-(S,R)-sulfoximine
-
cotreatment with L-buthionine-(S,R)-sulfoximine, 1-methyl-4-phenylpyridinium and fibroblast growth factor 9 inhibits increased neuron viability compared to the group treated with 1-methyl-4-phenylpyridinium and fibroblast growth factor 9, to levels comparable to those of the 1-methyl-4-phenylpyridinium-treated group
L-buthionine-R,S-sulfoximine
Q9NFN6
i.e. BSO, specific, irreversible
L-buthionine-R-sulfoximine
P0A6W9
-
L-buthionine-R-sulfoximine
P48506, P48507
-
L-buthionine-R-sulfoximine
P19468, P48508
mechanism-based, competitive, reversible
L-buthionine-S-sulfoximine
P0A6W9
strong inhibition
L-buthionine-S-sulfoximine
P48506, P48507
strong inhibition
L-buthionine-S-sulfoximine
P19468, P48508
mechanism-based, ATP-dependent, nearly irreversible inhibition in presence of Mg2+ and ATP, if ATP and Mg2+ are remove the activity is restored
L-buthionine-S-sulfoximine
-
; specific inhibitor
L-buthionine-S-sulfoximine
-
irrversible inactivation, no inhibition of mutant R366A
L-buthionine-S-sulfoximine
P0A6W9
mechanism-based inhibitor, in contrary to the mammalian enzyme form, the Escherichia coli enzyme is inhibited more weakly and slowly in presence of Mg2+, replacement of the metal by Mn2+ leads to increased binding affinity and inactivation rate
L-buthionine-S-sulfoximine
-
competitive with L-glutamate
L-buthionine-S-sulfoximine
-
mechanism-based inhibitor. The crystal structure of the enzyme complex to 2.2 A resolution confirms that L-buthionine-S-sulfoximine is phosphorylated on the sulfoximine nitrogen to generate the inhibitory species and reveals contacts that likely contribute to transition state stabilization
L-buthionine-SR-sulfoximine
-
; irreversible inactivation, ATP-dependent, a N-phosphorylated reaction intermediate is tightly bound to the enzyme, mechanism-based
L-buthionine-SR-sulfoximine
-
specific
L-cysteine
-
varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. After subacute exposure, low doses increases GCL activity and GSH content in liver by 48.3% and 54.4%, respectively. High doses reduce GCL activities significantly in liver and kidney to 31.2% and 43.0% of the control, respectively
L-cysteine
-
varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. Low doses activate high doses inhibits the enzyme
L-glutamic acid gamma-monohydroxamate
-
ATP-dependent irreversible inactivation, loss of 90% activity within 3 days, inactivation mechanism, no inactivation occurs in absence of ATP or with AMP-PNP
L-glutamine
P19468
inhibition of enzyme activity in tumor tissue
L-Homocysteate
-
-
L-Homocysteine sulfinate
-
-
L-methionine
-
inhibits expression of heavy subunit
lipopolysaccharides
-
inhibits expression of heavy subunit
-
methionine
-
inhibits induction of GSH1 expression, independently of GSH
methionine sulfoximine
-
and analogs, no effect on glutamine synthetase
methionine sulfoximine
-
-
methionine sulfoximine
-
of the 4 stereoisomers only L-methionine-S-sulfoximine inhibits
methionine sulfoximine
-
-
methionine sulfoximine
P97494, Q97SC0
-
methionine sulfoximine
P19468, P48508
competitive and reversible
MgATP2-
Q9W3K5
although the enzyme preparation shows a strict requirement for MgATP2- for gamma-glutamylcysteine synthesis, preincubation of the homogenate under phosphorylating conditions with MgATP2- also causes a maximal inhibition of 89%
MgATP2-
P97494
although the enzyme preparation shows a strict requirement for MgATP2- for gamma-glutamylcysteine synthesis, preincubation of the homogenates under phosphorylating conditions with MgATP2- also causes a maximal inhibition of 94%, 77%, 85%, 87%, 83% and 95% in cerebellum, hippocampus, brainstem, striatum, cortex and heart
N-Methyl-L-glutamate
-
-
N-[2(2-Aminoethyl)-dithioethyl]4-azido-2-nitrobenzeneamine
-
-
Na+
-
72.7% inhibition at 300 mM
Na+
-
69.2% inhibition at 300 mM
Na+
-
79.6% inhibition at 300 mM
NF-kappaB
-
inhibits induction of enzyme expression by other substances, e.g. buthionine sulfoximine or tert-butylhydroquinone
-
Ni2+
-
complete inactivation
NO
P97494, Q97SC0
-
ophthalmic acid
P19468, P48508
;
oxidative stress
-
heterozygous mutants with one allele inactivated are more susceptible to oxidative stresses in vitro as promastigotes and show decreased survival inside activated macrophages producing reactive oxygen or nitrogen species
-
Pb2+
-
in deer mice exposed to Pb, or Pb together with Cu and Zn via drinking water for 4 weeks. GCL activities are not significantly affected by treatments. Metal-contaminated soils do not lead to significant effects in pups via lactation, 50-day exposure alters glutathione content marginally, while 100-day exposure results in marked GCL activity depletion. After 100-day exposure, GCL activities of the medium soil-, high soil- and Pb-treated deer mice are only 53%, 40% and 46% of the control, respectively
Prothionine sulfoximine
-
-
Prothionine sulfoximine
-
i.e. S-n-propyl homocysteine sulfoximine; no effect on glutamine synthetase
S-(S-Methyl)cysteamine
-
-
S-butyl-DL-homocysteine-SR-sulfoximine
P97494, Q97SC0
-
S-butyl-DL-homocysteine-SR-sulfoximine
P19468, P48508
-
S-nitroso-L-cysteine
P19468, P48508
inactivation, prevented by pretreatment with ATP and L-SR-buthionine sulfoximine in absence of Mg2+
S-nitroso-L-cysteinylglycine
P19468, P48508
inactivation, prevented by pretreatment with ATP and L-SR-buthionine sulfoximine in absence of Mg2+
S-sulfo-homocysteine
P19468, P48508
-
S-sulfo-L-cysteine
P19468, P48508
-
S-sulfocysteine
-
no inhibition
S-sulfocysteine
-
-
S-sulfocysteine
-
D-enantiomer and L-enantiomer, ATP is not required for inactivation, noncovalent binding of close to 1 mol of inactivator per mol of enzyme, competitive with respect to L-Glu, complete protection with L-gamma-glutamyl-L-2-aminobutanoate, L-Glu + ATP, and ADP
S-sulfohomocysteine
-
no inhibition
S-sulfohomocysteine
-
-
S-sulfohomocysteine
-
D-enantiomer and L-enantiomer, ATP is not required for inactivation, noncovalent binding of close to 1 mol of inactivator per mol of enzyme, mixed-type inhibition
Selenocystamine
-
-
Thiocholine disulfide
-
-
threo-beta-Hydroxy-DL-glutamate
-
-
threo-gamma-Hydroxy-L-glutamate
-
-
trans-1-Amino-1,3-dicarboxycyclohexane
-
-
Trinitrobenzene sulfonate
-
addition of 10 mM Mg2+ results in a 16fold increase of inactivation rate, Lys-38 in the heavy subunit is significantly modified in presence of Mg2+
Trinitrobenzene sulfonate
P19468, P48508
inactivates the enzyme
Zn2+
-
0.2 mM, activity is reduced by 19%
Zn2+
-
21% residual activity
Monodansylcystamine
-
-
additional information
P0A6W9
no inhibition by cysteamine or slowly at high concentration
-
additional information
P97494, Q97SC0
no inhibition by alpha-ethyl-methionine sulfoximine
-
additional information
P19468, P48508
inhibition mechanisms, no inhibition by L-homocysteine sulfonate
-
additional information
-
no inacivationwith ATP alone or with L-aspartic acid gamma-monohydroxamate
-
additional information
-
the inhibition mode and potency of the different sulfoximines is highly dependent on the stereochemistry at the sulfoximine sulfur atom, overview
-
additional information
-
protein-supplemented diet inhibits expression of heavy subunit
-
additional information
P0A6W9
no inhibition by L-buthionine-R-sulfoximine
-
additional information
-
the genotype of GLCLC is associated with drug sensitivity or resistance, respectively, sensitivity of different genotypes to diverse drugs, overview
-
additional information
-
no significant inhibition by cystamine, L-methionine-SR-sulfoximine and GSH
-
additional information
-
oxidative stress dramatically affects GCL holoenzyme formation and activity
-
additional information
P19468
7,12-dimethylbenz[a]anthracene does not affect GCS enzyme activity in gut tissue
-
additional information
-
no inhibition by DTT
-
additional information
-
no inhibition by buthionine sulfoximine
-
additional information
-
no inhibition by DTT
-
additional information
-
decrease of enzyme activity in hypoxia: 20% after 6 h, 17% after 12 h, 23% after 24 h, hypoxia-induced decrease in enzyme activity may be prevented by MAPK inhibition and catalase
-
additional information
D4N891
insensitive to feedback inhibition caused by GSH even at 20 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-(4-amino-2-methyl-5-pyridimidyl)-methyl-3-(2-chloroethyl)-3-nitrosurea
-
induces expression of heavy subunit
2,3-dimethoxy-1,4-naphthoquinone
-
induces expression of heavy and light subunit
2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetamide
-
i.e. metolachlor, a herbicide that decreases the plant growth and and biomass, induction of enzyme expression, enhanced enzyme activity leads to enhanced detoxification activity
2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide
-
i.e. acetochlor, a herbicide that decreases the plant growth and and biomass, induction of enzyme expression, enhanced enzyme activity leads to enhanced detoxification activity
4-hydroxy-2-nonenal
-
i.e. 4-HNE, inductor of enzyme expression, signals through the JNK pathway, most effective at 0.02 mM, time-dependence is different for GCLC and GCLM, overview, also activates the transcription factor complex AP-1 which itself activates expression of both enzyme subunits
4-hydroxy-2-nonenal
-
induces expression of heavy and light subunit
4-hydroxy-2-nonenal
-
4-hydroxy-2-nonenal causes a rapid dose- and time-dependent increase in A549 cell GCL activity. Maximal activation of GCL occurs at 30 min in response to 50 microM 4-hydroxy-2-nonenal
6-Hydroxydopamine
-
induces expression of heavy subunit
activator protein 1
-
i.e. AP-1, is required for basal expression of the enzyme
-
adriamycin
-
induces expression of heavy subunit
AP-1
-
transcription factor complex including Jun family members, drives expression of both enzyme subunit encoding genes, AP-1 complex is activated by 4-hydroxy-2-nonenal, enzyme induction can be blocked by membrane-permeable peptide-based JNK inhibitor JNKi, but not by inhibitors SB202190 or PD98059
-
AP-1
-
transcription factor induces enzyme expression
-
apigenin
-
nearly 2fold induction of the heavy subunit gene promotor and heavy subunit expression
apocynin
-
induces expression of heavy subunit
beta-Naphthoflavone
-
induces expression of heavy subunit
buthionine sulfoximine
-
induction of enzyme expression
buthionine sulfoximine
-
induces expression of heavy and light subunit
butylated hydroxyanisole
-
induces expression of heavy and light subunit
butylated hydroxytoluene
-
induces expression of heavy subunit
cadmium aerosols
-
2.4 mg Cd/m3, enhance in the lung the expression of the enzyme's heavy, catalytic subunit gamma-GCS-HS by 4.5fold after 15 min, 8fold after 6 h, increase in enzyme activity and GSH production rate
-
cafestol
-
coffee component, induction of the enzyme in vivo, especially in the liver up to 2.4fold, increase in expression of both enzyme subunits
caffeic acid
-
treatment of the cells with 100 and 500 microg/ml of caffeic acid increases gamma-GCS activities by 1.4- and 1.8fold compared to the control group, respectively. At the same doses of caffeic acid, the treated cells show increased levels of glutathione by 1.7- and 2.7fold compared to the control, respectively
carbon tetrachloride
-
a single dose of 1589 mg/kg body weight of carbon tetrachloride causes changes in CGL activity and glutathione content in multiple organs of deer mice. Hepatic GCL activity and GSH content are depleted substantially, renal GCL activity increases. Blood, brain and heart GCL activities increase, whereas GSH contents decrease significantly
cigarette smoke condensate
-
induces expression of heavy subunit
-
diethyl maleate
-
induction of enzyme expression
diethyl maleate
-
induces expression of heavy and light subunit
erythropoietin
-
induces expression of heavy subunit
-
Ethacrynic acid
-
induces expression of heavy subunit
ethanol
-
feeding in vivo increases the enzyme expression, treatment of hepatocytes induces the expression of only the heavy enzyme subunit
ethoxyquin
-
induces expression of heavy subunit
Gly
-
stimulates
Gly
-
no effect
H2O2
P48506, P48507
induction of enzyme expression, increase in activity in V79 cells independent on transcription level
H2O2
-
induction of in enzyme expression and activity
H2O2
-
induces expression of heavy and light subunit
H2O2
-
40-50% increase in intracellular concentration induces enzyme expression 2fold to upregulate GSH production, GSH is required for detoxification, increase is reversible or preventable by peroxide-eliminating substances
hydrocortisone
-
treatment of hepatocytes induces the expression of only the heavy enzyme subunit
Insulin
-
treatment of hepatocytes induces the expression of only the heavy enzyme subunit
-
interleukin-1 beta
-
induces expression of heavy subunit
-
iodoacetamide
-
induces expression of heavy subunit
kaempferol
-
2fold induction of the heavy subunit gene promotor and heavy subunit expression
kahweol
-
coffee component, induction of the enzyme in vivo, especially in the liver up to 2.4fold, increase in expression of both enzyme subunits
L-cysteine
-
varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. After subacute exposure, low doses increases GCL activity and GSH content in liver by 48.3% and 54.4%, respectively. High doses reduce GCL activities significantly in liver and kidney to 31.2% and 43.0% of the control, respectively
L-cysteine
-
varying glutamic acid concentrations from 5 to 80 mM do not affect GCL activities markedly, whereas cysteine concentrations from 2.5 to 40 mM influence GCL activities substantially in a tissue-dependent manner, about 20 mM L-Cys is optimal in the different tissue, overview. Low doses activate high doses inhibits the enzyme
L-glutamine
P19468
enhanced enzyme activity in jejunal mucosa
mcCDC34
-
an ubiquitine conjugated protein, induces gamma-glutamylcysteine synthetase expression only in glutathione synthetase-dficient mutants, not in the wild-type
-
menadione
-
induces expression of heavy and light subunit
nitric oxide
-
induces expression of heavy and light subunit via direct exposure or interleukin-1 induced
oltipraz
-
induces expression of heavy subunit
onion extract
-
containing flavonoids, which increase the expression of both subunits of the enzyme in COS-1 cells
-
oxidative stress
-
activation of GCL occurrs within min of treatment and without any change in GCL protein levels, and coincides with an increase in the proportion of GCL catalytic subunit in the holoenzyme form. Likewise, GCL modifier subunit shifts from the monomeric form to holoenzyme and higher molecular weight species. Neither GCL activation, nor the formation of holoenzyme, requires a covalent intermolecular disulfide bridge between GCL catalytic subunit and GCL modifier subunit. In immunoprecipitation studies, a neutralizing epitope associated with enzymatic activity is protected following cellular oxidative stress. Thus, the N-terminal portion of GCL catalytic subunit may undergo a change that stabilizes the GCL holoenzyme. Results suggest a dynamic equilibrium between low- and high-activity forms of GCL, which is altered by transient oxidative stress
-
oxidized low density lipoprotein
-
induces expression of heavy subunit
-
phorone
-
induces expression of heavy subunit
Prostaglandin A2
-
induces expression of heavy subunit
pyrrolidine dithiocarbamate
-
time-, dose-, and Cu2+-dependent induction and increase in expression levels of the 2 subunits of the enzyme in HepG2 cells, mechanism, can be partially blocked by N-acetylcysteine and by copper chelator bathocuproine disulfonic acid
pyrrolidine dithiocarbamate
-
induces expression of heavy and light subunit
quercetin
-
3fold induction of the heavy subunit gene promotor and heavy subunit expression, best at 0.05 mM, induction even of a distal part of the promotor sequence containing only 2 antioxidant-response/electrophile-response elements, i.e. ARE/EpRE
tert-butyl hydroquinone
-
induces expression of heavy and light subunit
tert-butylhydroquinone
-
induction of enzyme expression
tert-butylhydroquinone
-
induces expression of heavy and light subunit
tert-butylhydroquinone
-
i.e. TBH, exerts a dose- and time-dependent increase in the mRNA level and promotor activity of the 2 genes encoding the enzyme subunits
Thioacetamide
-
induction of enzyme expression
methylmercuric hydroxide
-
induces expression of heavy subunit
additional information
-
two-thirds partial hepatectomy increases the enzyme expression
-
additional information
-
no increase in gene promotor activity by myricetin and sugar conjugates of quercetin, quercetin-3-glucoside and quercetin-3-rhamnoglucoside
-
additional information
-
multiple cis- and trans-elements have up-regulating effect on expression of the heavy catalytic subunit and of the regulatory light subunit, ionization radiation induces expression of heavy subunit, overview, effect of miscellaneous treatments on enzyme mRNA expression, overview
-
additional information
-
ionization radiation induces expression of heavy subunit, effect of miscellaneous treatments on enzyme mRNA expression, overview
-
additional information
-
effect of miscellaneous treatments on enzyme mRNA expression, overview
-
additional information
-
no induction of enzyme production in HepG2 cells by overexpression of human cytochrome 3A4
-
additional information
-
In response to redox environment, AtGCL undergoes a reversible conformational change that modulates the enzymatic activity of the monomer
-
additional information
-
the enzyme is induced by 4-hydroxy-2-nonenal through the c-Jun N-terminal kinase pathway, the regulation involves SHP-1, the protein-tyrosine phosphatase SH' domain containing phosphatase-1 in HBE1 cells, mechanism, overview
-
additional information
-
resveratrol and 4-hydroxy-2-nonenal both increases GSH and the mRNA contents of both the catalytic GCLC and modulatory GCLM subunit of GCL, both agents show synergictic effects when applied together, overview. The cis-element Nrf2/EpRE signalling is involved in resveratrol-mediated induction of GCL genes
-
additional information
-
induction of Gclc by homocysteine, ARE4 plays a direct role in mediating the induction, Nrf2 signalling is critical in homocysteine-induced activation of ARE4, overview
-
additional information
B2ZG39
both GCLC gene expression and total GSH levels increase 4 and 1.5fold, respectively, in response to hyperthermal stress, overview
-
additional information
-
GCLC expression is 3fold up-regulated 1 h after induction of edematous pancreatitis
-
additional information
-
under low glucose levels insulin induces an approximate 2fold increase in expression of gamma-glutamylcysteine ligase catalytic subunit GCLc mRNA and protein, which does not lead to increased GSH levels in the cell
-
additional information
-
subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP
-
additional information
-
extracts of Ginkgo biloba induces GCL catalytic subunit, GCLC, in HepG2 and Hep1c1c7 cell lines
-
additional information
Q1W2L8
GCL forms a homodimer under oxidizing conditions, and is activated more than threefold
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
7.3
(R)-beta-amino-iso-butyrate
-
-
13.3
(S)-beta-amino-iso-butyrate
-
-
2.9
2-aminobutanoate
-
liver enzyme
6.36
2-aminobutanoate
-
-
1.3
4-aminobutyrate
-
pH 8.2, 37C
20
4-aminobutyrate
-
mutant R366A, pH 8.0, 37C
150
4-aminobutyrate
-
wild-type enzyme, pH 8.0, 37C
0.0001
ATP
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
0.00014
ATP
-
pH 8.0, 25C, wild-type enzyme
0.00019
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
0.00024
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
0.00025
ATP
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
0.00046
ATP
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
0.00053
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
0.01
ATP
-
-
0.06
ATP
-
pH 8.4, 37C, mutant enzyme D520stop
0.065
ATP
-
pH 8.4, 37C, mutant enzyme E494stop; pH 8.4, 37C, mutant enzyme G441stop
0.066
ATP
-
pH 8.4, 37C, mutant enzyme Y464stop
0.069
ATP
-
pH 8.4, 37C, mutant enzyme K526A
0.07
ATP
-
-
0.071
ATP
-
wild-type, pH 8.0, 37C
0.075
ATP
D7P1H2
-
0.08
ATP
-
wild-type, pH 8.0
0.082
ATP
-
pH 8.4, 37C, mutant enzyme R508stop
0.1
ATP
P0A6W9
strain B
0.11
ATP
-
mutant R491A, pH 8.0, 37C
0.14
ATP
-
mutant R179A, pH 8.0, 37C
0.145
ATP
P74515
pH 7.5, 25C, wild-type enzyme
0.2
ATP
-
-
0.2
ATP
P19468, P48508
holoenzyme
0.23
ATP
-
pH 8.4, 25C
0.25
ATP
-
25C, pH 8.2; pH 8.2, 25C
0.26
ATP
-
mutant H370L, CGL holoenzyme, pH 8.0, 37C
0.279
ATP
P74515
pH 7.5, 25C, mutant H121Q
0.3
ATP
-
mutant P138L, CGL holoenzyme, pH 8.0, 37C
0.31
ATP
P74515
pH 7.5, 25C, mutant H121A
0.35
ATP
-
-
0.352
ATP
P74515
pH 7.5, 25C, mutant T117S
0.4
ATP
P48506, P48507
holoenzyme
0.4
ATP
-
pH 8.2, 37C
0.44
ATP
-
wild-type, CGL holoenzyme, pH 8.0, 37C
0.445
ATP
P74515
pH 7.5, 25C, mutant R167K
0.5
ATP
-
mutant R127C, CGL holoenzyme, pH 8.0, 37C
0.622
ATP
-
pH 8.4, 37C, mutant enzyme H144A
0.71
ATP
Q26820
-
0.82
ATP
-
mutant P414L, catalytic subunit, pH 8.0, 37C
0.87
ATP
-
37C, pH 7.2, holoenzyme
0.92
ATP
-
pH 8.2
0.969
ATP
P74515
pH 7.5, 25C, mutant R248K
1.2
ATP
-
mutant R487A, pH 8.0, 37C
1.3
ATP
-
mutant R474A, pH 8.0, 37C
1.3
ATP
-
-
1.4
ATP
-
wild-type enzyme and mutant C319A, pH 8.0, 37C
1.41
ATP
-
-
2.68
ATP
-
wild-type, catalytic subunit, pH 8.0, 37C
2.8
ATP
-
mutant R366A, pH 8.0, 37C
3.57
ATP
-
mutant P138L, catalytic subunit, pH 8.0, 37C
4.47
ATP
-
mutant R127C, catalytic subunit, pH 8.0, 37C
5
ATP
-
37C, pH 7.2, catalytic subunit GCLC
7
ATP
-
mutant T323A, pH 8.0, 37C
25.3
ATP
-
pH 7, mutant enzyme C364S
31.6
ATP
-
pH 7, mutant enzyme C349S
37.5
ATP
-
pH 7, mutant enzyme C251S
40.3
ATP
-
pH 7, mutant enzyme C102S
42
ATP
-
pH 7, wild-type enzyme
0.3
cysteine
-
enzyme from embryo homogenate and from visceral yolk sac homogenate
2.7
cysteine
-
pH 7.0, 25C, mutant DELTA85
0.86
gamma-L-Glu-L-Cys
-
catalytic subunit, pH 8.0, 37C
1.3
gamma-L-Glu-L-Cys
-
holoenzyme, pH 8.0, 37C
0.75
glutamate
-
enzyme from embryo homogenate
1.38
glutamate
-
enzyme from visceral yolk sac homogenate
9.1
glutamate
-
pH 7.0, 25C, mutant DELTA85
0.14
L-2-aminobutanoate
-
-
0.8
L-2-aminobutanoate
-
recombinant heavy subunit
1
L-2-aminobutanoate
-
-
1
L-2-aminobutanoate
-
GTP
1.3
L-2-aminobutanoate
-
strain W
1.3
L-2-aminobutanoate
-
-
1.4
L-2-aminobutanoate
-
strain KM
1.4
L-2-aminobutanoate
-
-
1.4
L-2-aminobutanoate
-
L-Glu, kidney enzyme
1.4
L-2-aminobutanoate
-
L-Glu, holoenzyme
1.5
L-2-aminobutanoate
-
-
1.5
L-2-aminobutanoate
-
2-aminobutanoate, kidney enzyme; L-Glu, liver enzyme
10
L-2-aminobutanoate
-
-
10.4
L-2-aminobutanoate
-
-
10.4
L-2-aminobutanoate
-
L-Glu
0.8
L-2-aminobutyrate
-
37C
1.4
L-2-aminobutyrate
P48506
37C
1.7
L-2-aminobutyrate
-
recombinant catalytic subunit, pH 8.0, 37C
3.4
L-2-aminobutyrate
-
recombinant holoenzyme, pH 8.0, 37C
3.6
L-2-aminobutyrate
-
recombinant wild-type holoenzyme, pH 8.0, 37C
5
L-2-aminobutyrate
-
recombinant mutant C553G holoenzyme, pH 8.0, 37C
5.4
L-2-aminobutyric acid
-
wild-type enzyme, pH 8.0, 37C
6.1
L-2-aminobutyric acid
-
mutant C319A, pH 8.0, 37C
0.25
L-alpha-aminobutyrate
-
mutant R127C, pH 8.0, 37C
0.31
L-alpha-aminobutyrate
-
-
1
L-alpha-aminobutyrate
P19468, P48508
-
1.3
L-alpha-aminobutyrate
P0A6W9
-
2.3
L-alpha-aminobutyrate
P48506, P48507
-
2.39
L-alpha-aminobutyrate
-
wild-type enzyme, pH 8.0, 37C
6
L-alpha-aminobutyrate
-
wild-type enzyme, pH 8.0, 37C, in presence of Mn2+
7.5
L-alpha-aminobutyrate
-
mutant T323A, pH 8.0, 37C
9.4
L-alpha-aminobutyrate
-
mutant E489A, pH 8.0, 37C, in presence of Mn2+
10
L-alpha-aminobutyrate
-
wild-type, pH 8.0, 37C
10
L-alpha-aminobutyrate
-
wild-type enzyme, pH 8.0, 37C, in presence of Mg2+
14
L-alpha-aminobutyrate
-
mutant Q321A, pH 8.0, 37C, in presence of Mn2+
15
L-alpha-aminobutyrate
-
mutant R487A, pH 8.0, 37C
15
L-alpha-aminobutyrate
-
mutant E489A, pH 8.0, 37C, in presence of Mg2+
18
L-alpha-aminobutyrate
-
mutant Q321A, pH 8.0, 37C, in presence of Mg2+
34
L-alpha-aminobutyrate
-
mutant R366A, pH 8.0, 37C
56
L-alpha-aminobutyrate
-
mutant R474A, pH 8.0, 37C
380
L-alpha-aminobutyrate
-
mutant R179A, pH 8.0, 37C
0.31
L-aminobutanoate
-
-
0.05
L-Cys
-
mutant R127C, catalytic subunit, pH 8.0, 37C
0.07
L-Cys
-
wild-type, CGL holoenzyme, pH 8.0, 37C
0.08
L-Cys
-
mutant P138L, catalytic subunit, pH 8.0, 37C
0.09
L-Cys
-
-
0.1
L-Cys
-
strain W
0.1
L-Cys
-
wild-type, catalytic subunit, pH 8.0, 37C
0.12
L-Cys
-
mutant R127C, CGL holoenzyme, pH 8.0, 37C
0.138
L-Cys
-
pH 8.4, 37C, mutant enzyme Y464stop
0.147
L-Cys
-
pH 8.4, 37C, mutant enzyme K526A
0.15
L-Cys
-
-
0.16
L-Cys
-
mutant H370L, CGL holoenzyme, pH 8.0, 37C
0.161
L-Cys
-
pH 8.4, 37C, mutant enzyme D520stop
0.166
L-Cys
-
pH 8.4, 37C, mutant enzyme G441stop
0.17
L-Cys
-
wild-type, pH 8.0
0.17
L-Cys
-
mutant P138L, CGL holoenzyme, pH 8.0, 37C; mutant P414L, catalytic subunit, pH 8.0, 37C
0.171
L-Cys
-
pH 8.4, 37C, mutant enzyme E494stop
0.19
L-Cys
-
-
0.2
L-Cys
-
strain KM
0.2
L-Cys
-
-
0.2
L-Cys
-
ATP, holoenzyme and recombinant heavy subunit
0.2
L-Cys
-
L-Cys
0.22
L-Cys
-
25C, pH 8.2
0.26
L-Cys
-
pH 8.4, 37C, mutant enzyme R508stop
0.3
L-Cys
-
-
0.41
L-Cys
-
-
0.53
L-Cys
-
pH 8.2
0.69
L-Cys
-
-
1
L-Cys
-
pH 8.4, 37C, mutant enzyme H144A
4 - 5.4
L-Cys
-
pH 7, mutant enzyme C364S
39.2
L-Cys
-
pH 7, mutant enzyme C251S
46.1
L-Cys
-
pH 7, mutant enzyme C349S
46.9
L-Cys
-
pH 7, wild-type enzyme
57.3
L-Cys
-
pH 7, mutant enzyme C102S
0.0001
L-cysteine
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT; pH 8.0, 25C, wild-type enzyme
0.00011
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y; pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
0.00014
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F; pH 8.0, 25C, wild-type enzyme, in presence of DTT
0.00016
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
0.059
L-cysteine
P74515
pH 7.5, 25C, wild-type enzyme
0.07
L-cysteine
-
-
0.09
L-cysteine
P0A6W9
strain B
0.1
L-cysteine
P0A6W9
strain W
0.1
L-cysteine
P48506, P48507
holoenzyme
0.1
L-cysteine
-
pH 8.2, 37C
0.116
L-cysteine
P74515
pH 7.5, 25C, mutant H121Q
0.12
L-cysteine
-
-
0.13
L-cysteine
P48506, P48507
heavy subunit
0.14
L-cysteine
-
pH 8.4, 25C
0.14
L-cysteine
-
-
0.15
L-cysteine
-
-
0.156
L-cysteine
-
-
0.186
L-cysteine
P74515
pH 7.5, 25C, mutant T117S
0.19
L-cysteine
-
-
0.2
L-cysteine
P0A6W9
strain KM
0.2
L-cysteine
P19468, P48508
heavy subunit and holoenzyme
0.22
L-cysteine
-
37C, pH 7.2, holoenzyme
0.22
L-cysteine
-
pH 8.2, 25C
0.27
L-cysteine
-
37C, pH 7.2, catalytic subunit GCLC
0.399
L-cysteine
D7P1H2
-
0.4
L-cysteine
-
-
0.41
L-cysteine
-
-
0.5
L-cysteine
-
recombinant catalytic subunit, pH 8.0, 37C
0.5
L-cysteine
-
recombinant mutant C553G holoenzyme, pH 8.0, 37C
0.69
L-cysteine
Q26820
-
0.707
L-cysteine
P74515
pH 7.5, 25C, mutant H121A
0.8
L-cysteine
-
recombinant holoenzyme, pH 8.0, 37C
0.8
L-cysteine
-
recombinant wild-type holoenzyme, pH 8.0, 37C
0.857
L-cysteine
P74515
pH 7.5, 25C, mutant R248K
1.95
L-cysteine
P74515
pH 7.5, 25C, mutant R167K
0.03
L-Glu
-
-
0.23
L-Glu
-
holoenzyme, pH 8.0, 37C
0.24
L-Glu
-
-
0.44
L-Glu
-
mutant H370L, CGL holoenzyme, pH 8.0, 37C
0.46
L-Glu
-
wild-type, CGL holoenzyme, pH 8.0, 37C
0.5
L-Glu
-
-
0.63
L-Glu
-
mutant R127C, pH 8.0, 37C
0.65
L-Glu
-
mutant P138L, CGL holoenzyme, pH 8.0, 37C
0.68
L-Glu
-
mutant P138L, catalytic subunit, pH 8.0, 37C
0.7
L-Glu
-
strain W
0.7
L-Glu
-
recombinant wild-type holoenzyme, pH 8.0, 37C
0.75
L-Glu
-
pH 8.2
0.77
L-Glu
-
mutant P414L, catalytic subunit, pH 8.0, 37C
0.9
L-Glu
-
recombinant mutant C553G holoenzyme, pH 8.0, 37C
0.94
L-Glu
-
-
1.14
L-Glu
-
wild-type, catalytic subunit, pH 8.0, 37C
1.2
L-Glu
-
-
1.2
L-Glu
-
L-2-aminobutanoate
1.2
L-Glu
-
L-2-aminobutanoate
1.21
L-Glu
-
wild-type, pH 8.0
1.38
L-Glu
-
mutant R127C, catalytic subunit, pH 8.0, 37C; mutant R127C, CGL holoenzyme, pH 8.0, 37C
1.7
L-Glu
-
strain KM
1.93
L-Glu
-
mutant C266A, pH 8.0
2 - 3
L-Glu
-
pH 8.4, 37C, mutant enzyme Y464stop
2.15
L-Glu
-
mutant C266S, pH 8.0
2.2
L-Glu
-
catalytic subunit, pH 8.0, 37C
2.6
L-Glu
-
wild-type enzyme, pH 8.0, 37C
5.3
L-Glu
-
25C, pH 8.2
5.9
L-Glu
-
mutant C319A, pH 8.0, 37C
7
L-Glu
-
pH 7, mutant enzyme C364S
7.16
L-Glu
-
wild-type enzyme, pH 8.0, 37C
8.5
L-Glu
-
pH 7, mutant enzyme C102S
9.1
L-Glu
-
pH 7, wild-type enzyme
11.2
L-Glu
-
pH 7, mutant enzyme C349S
13.9
L-Glu
-
pH 7, mutant enzyme C251S
18.2
L-Glu
-
recombinant heavy subunit
22
L-Glu
-
pH 8.4, 37C, mutant enzyme E494stop
24
L-Glu
-
pH 8.4, 37C, mutant enzyme K526A
28.9
L-Glu
-
pH 8.4, 37C, mutant enzyme D520stop
34.7
L-Glu
-
pH 8.4, 37C, mutant enzyme R508stop
77
L-Glu
-
pH 8.4, 37C, mutant enzyme G441stop
229
L-Glu
-
pH 8.4, 37C, mutant enzyme H144A
0.0032
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
0.0039
L-glutamate
-
pH 8.0, 25C, wild-type enzyme
0.004
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F; pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
0.0041
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
0.0051
L-glutamate
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
0.0053
L-glutamate
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
0.24
L-glutamate
Q26820
-
0.24
L-glutamate
-
wild-type, pH 8.0, 37C
0.24
L-glutamate
-
wild-type enzyme, pH 8.0, 37C, in presence of Mg2+
0.48
L-glutamate
-
37C, pH 7.2, holoenzyme
0.5
L-glutamate
P0A6W9
strain B
0.5
L-glutamate
P74515
pH 7.5, 25C, mutant R167K
0.61
L-glutamate
-
mutant R491A, pH 8.0, 37C
0.7
L-glutamate
P0A6W9
strain W
0.7
L-glutamate
-
recombinant holoenzyme, pH 8.0, 37C
0.82
L-glutamate
-
pH 8.4, 25C
0.89
L-glutamate
-
mutant E489A, pH 8.0, 37C, in presence of Mn2+
0.91
L-glutamate
-
25C, recombinant His-tagged wild-type enzyme
0.92
L-glutamate
-
25C, recombinant His-tagged wild-type catalytic subunit
0.94
L-glutamate
-
-
0.953
L-glutamate
P74515
pH 7.5, 25C, wild-type enzyme
0.97
L-glutamate
-
25C, recombinant His-tagged wild-type catalytic subunit with recombinant His-tagged mutant modifier subunit C213S/C214S/C267S
1
L-glutamate
-
wild-type enzyme, pH 8.0, 37C, in presence of Mn2+
1.1
L-glutamate
-
mutant E489A, pH 8.0, 37C, in presence of Mg2+; mutant Q321A, pH 8.0, 37C, in presence of Mn2+
1.18
L-glutamate
P74515
pH 7.5, 25C, mutant H121Q
1.2
L-glutamate
Q9NFN6
pH 8.0, 37C
1.3
L-glutamate
-
mutant R487A, pH 8.0, 37C
1.4
L-glutamate
-
-
1.4
L-glutamate
-
holoenzyme
1.6
L-glutamate
-
-
1.6
L-glutamate
-
mutant R474A, pH 8.0, 37C
1.6
L-glutamate
-
mutant Q321A, pH 8.0, 37C, in presence of Mg2+
1.6
L-glutamate
-
37C, pH 7.2, catalytic subunit GCLC
1.7
L-glutamate
P0A6W9
strain KM
1.7
L-glutamate
-
mutant T323A, pH 8.0, 37C
1.8
L-glutamate
-
pH 8.2, 37C
1.9
L-glutamate
P48506, P48507
holoenzyme
1.9
L-glutamate
-
-
2.3
L-glutamate
-
37C
2.3
L-glutamate
-
-
2.4
L-glutamate
P48506
37C
3.2
L-glutamate
P48506, P48507
heavy subunit
3.5
L-glutamate
-
recombinant catalytic subunit, pH 8.0, 37C
3.76
L-glutamate
P74515
pH 7.5, 25C, mutant R248K
5.2
L-glutamate
-
mutant R179A, pH 8.0, 37C
5.3
L-glutamate
-
pH 8.2, 25C
6.1
L-glutamate
P74515
pH 7.5, 25C, mutant T117S
8.5
L-glutamate
-
-
10.4
L-glutamate
-
-
11
L-glutamate
-
mutant E93A, pH 8.0, 37C, in presence of Mg2+
15.2
L-glutamate
P74515
pH 7.5, 25C, mutant H121A
18.2
L-glutamate
P19468, P48508
heavy subunit
18.2
L-glutamate
-
catalytic subunit
22
L-glutamate
-
-
33
L-glutamate
D7P1H2
-
130
L-glutamate
-
mutant R366A, pH 8.0, 37C
0.071
MgATP2-
-
wild-type enzyme, pH 8.0, 37C, in presence of Mg2+
0.32
MgATP2-
-
mutant E93A, pH 8.0, 37C, in presence of Mg2+
2
MgATP2-
-
mutant E489A, pH 8.0, 37C, in presence of Mg2+
45
MgATP2-
-
above, mutant Q321A, pH 8.0, 37C, in presence of Mg2+
0.022
MnATP2-
-
wild-type enzyme, pH 8.0, 37C, in presence of Mn2+
0.1
MnATP2-
-
mutant E489A, pH 8.0, 37C, in presence of Mn2+
1.2
MnATP2-
-
mutant Q321A, pH 8.0, 37C, in presence of Mn2+
additional information
additional information
P19468, P48508
kinetics, kinetic mechanism
-
additional information
additional information
-
kinetics for the wild-type and mutant enzymes
-
additional information
additional information
-
kinetics, recombinant enzyme
-
additional information
additional information
-
kinetics; kinetics, wild-type enzyme and mutant C319A
-
additional information
additional information
-
kinetics
-
additional information
additional information
P0A6W9
Km values for diverse substrates in presence of Mg2+, or Mn2+, or both, kinetics
-
additional information
additional information
Q9NFN6
preliminary steady state kinetics
-
additional information
additional information
P74515
steady-state kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.14
4-aminobutyrate
-
wild-type, pH 8.0, 37C
0.59
4-aminobutyrate
-
mutant R366A, pH 8.0, 37C
6.08
4-aminobutyrate
-
mutant R366A, pH 8.0, 37C
0.008
ATP
P74515
pH 7.5, 25C, mutant R248K
0.038
ATP
P74515
pH 7.5, 25C, mutant R167K
0.098
ATP
P74515
pH 7.5, 25C, mutant H121A
0.137
ATP
P74515
pH 7.5, 25C, wild-type enzyme
0.225
ATP
P74515
pH 7.5, 25C, mutant T117S
0.382
ATP
P74515
pH 7.5, 25C, mutant H121Q
1.9
ATP
-
37C, pH 7.2,catalytic subunit GCLC
4.4
ATP
-
pH 7, mutant enzyme C364S
5.5
ATP
-
pH 7, mutant enzyme C349S
5.8
ATP
-
pH 7, mutant enzyme C102S
6.3
ATP
-
pH 7, mutant enzyme C251S
6.8
ATP
-
pH 7, wild-type enzyme
8.2
ATP
-
37C, pH 7.2, holoenzyme
22.4
ATP
-
25C, pH 8.2; pH 8.2, 25C
23
ATP
-
wild-type and mutant enzyme, pH 8.0, 37C
24.2
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
27.2
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
28.7
ATP
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
30.1
ATP
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
30.5
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
39.7
ATP
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
46.9
ATP
-
pH 8.0, 25C, wild-type enzyme
23
L-alpha-aminobutyrate
-
wild-type and mutant enzyme, pH 8.0, 37C
3.6
L-Cys
-
pH 7, mutant enzyme C349S
4
L-Cys
-
pH 7, mutant enzyme C251S
4.1
L-Cys
-
pH 7, mutant enzyme C364S
4.5
L-Cys
-
pH 7, wild-type enzyme
5.5
L-Cys
-
pH 7, mutant enzyme C102S
25.3
L-Cys
-
25C, pH 8.2
0.01
L-cysteine
P74515
pH 7.5, 25C, mutant R248K
0.025
L-cysteine
P74515
pH 7.5, 25C, mutant R167K
0.09
L-cysteine
P74515
pH 7.5, 25C, mutant H121A
0.133
L-cysteine
P74515
pH 7.5, 25C, mutant T117S
0.335
L-cysteine
P74515
pH 7.5, 25C, mutant H121Q
0.42
L-cysteine
P74515
pH 7.5, 25C, wild-type enzyme
1.9
L-cysteine
-
37C, pH 7.2, catalytic subunit GCLC
8.2
L-cysteine
-
37C, pH 7.2, holoenzyme
21.9
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
22.2
L-cysteine
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
24.2
L-cysteine
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
25.3
L-cysteine
-
pH 8.2, 25C
29.2
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
31.8
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
39.7
L-cysteine
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
46.6
L-cysteine
-
pH 8.0, 25C, wild-type enzyme
7350
L-cysteine
-
-
7920
L-cysteine
-
-
10190
L-cysteine
-
-
4.1
L-Glu
-
pH 7, mutant enzyme C364S
4.6
L-Glu
-
pH 7, mutant enzyme C102S
4.7
L-Glu
-
pH 7, mutant enzyme C349S
6.1
L-Glu
-
pH 7, wild-type enzyme
7.1
L-Glu
-
pH 7, mutant enzyme C251S
23
L-Glu
-
wild-type and mutant enzyme, pH 8.0, 37C
24.3
L-Glu
-
25C, pH 8.2
0.008
L-glutamate
P74515
pH 7.5, 25C, mutant R248K
0.045
L-glutamate
P74515
pH 7.5, 25C, mutant R167K
0.055
L-glutamate
-
mutant R491A, pH 8.0, 37C
0.127
L-glutamate
P74515
pH 7.5, 25C, mutant H121A
0.137
L-glutamate
P74515
pH 7.5, 25C, mutant T117S
0.188
L-glutamate
P74515
pH 7.5, 25C, mutant H121Q
0.24
L-glutamate
-
mutant R474A, pH 8.0, 37C
0.32
L-glutamate
-
mutant R366A, pH 8.0, 37C
0.35
L-glutamate
P74515
pH 7.5, 25C, wild-type enzyme
0.61
L-glutamate
-
mutant R179A, pH 8.0, 37C
0.79
L-glutamate
-
mutant T323A, pH 8.0, 37C
1.2
L-glutamate
-
mutant R487A, pH 8.0, 37C
1.9
L-glutamate
-
37C, pH 7.2, catalytic subunit GCLC
3.9
L-glutamate
-
wild-type, pH 8.0, 37C
6.08
L-glutamate
-
mutant R179A, pH 8.0, 37C; mutant T323A, pH 8.0, 37C
8.2
L-glutamate
-
37C, pH 7.2, holoenzyme
22.1
L-glutamate
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
22.7
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
23.8
L-glutamate
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
24.3
L-glutamate
-
pH 8.2, 25C
30.4
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
31.2
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
31.4
L-glutamate
-
pH 8.0, 25C, wild-type enzyme
34
L-glutamate
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
7350
L-glutamate
-
-
7920
L-glutamate
-
-
10190
L-glutamate
-
-
0.0066
Mg2+
-
mutant E489A, pH 8.0, 37C
0.078
Mg2+
-
mutant E93A, pH 8.0, 37C
0.08
Mg2+
-
mutant Q321A, pH 8.0, 37C
3.8
Mg2+
-
wild-type enzyme, pH 8.0, 37C
0.0053
MgATP2-
-
mutant E489A, pH 8.0, 37C
0.066
MgATP2-
-
mutant E93A, pH 8.0, 37C
0.24
MgATP2-
-
above, mutant Q321A, pH 8.0, 37C
3.8
MgATP2-
-
wild-type enzyme, pH 8.0, 37C
0.089
Mn2+
-
mutant E93A, pH 8.0, 37C
0.89
Mn2+
-
mutant E489A, pH 8.0, 37C
1.5
Mn2+
-
mutant Q321A, pH 8.0, 37C
2.5
Mn2+
-
wild-type enzyme, pH 8.0, 37C
6.08
Mn2+
-
mutant E489A, pH 8.0, 37C
0.89
MnATP2-
-
mutant E489A, pH 8.0, 37C
1.5
MnATP2-
-
mutant Q321A, pH 8.0, 37C
2.4
MnATP2-
-
wild-type enzyme, pH 8.0, 37C
6.08
MnATP2-
-
mutant E489A, pH 8.0, 37C
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0086
ATP
P74515
pH 7.5, 25C, mutant R248K
4
0.0861
ATP
P74515
pH 7.5, 25C, mutant R167K
4
0.317
ATP
P74515
below, pH 7.5, 25C, mutant H121A
4
0.639
ATP
P74515
pH 7.5, 25C, mutant T117S
4
1.37
ATP
P74515
pH 7.5, 25C, mutant H121Q
4
3.52
ATP
P74515
pH 7.5, 25C, wild-type enzyme
4
46.6
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
4
62.4
ATP
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
4
120.4
ATP
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
4
127.1
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
4
142.9
ATP
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
4
335
ATP
-
pH 8.0, 25C, wild-type enzyme
4
397
ATP
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
4
0.0117
L-cysteine
P74515
pH 7.5, 25C, mutant R248K
74
0.0128
L-cysteine
P74515
pH 7.5, 25C, mutant R167K
74
0.127
L-cysteine
P74515
pH 7.5, 25C, mutant H121A
74
0.717
L-cysteine
P74515
pH 7.5, 25C, mutant T117S
74
2.89
L-cysteine
P74515
pH 7.5, 25C, mutant H121Q
74
7.12
L-cysteine
P74515
pH 7.5, 25C, wild-type enzyme
74
172.9
L-cysteine
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
74
198.8
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W
74
199.1
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
74
222
L-cysteine
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
74
288.6
L-cysteine
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
74
396.9
L-cysteine
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
74
466
L-cysteine
-
pH 8.0, 25C, wild-type enzyme
74
0.0009
L-glutamate
P74515
pH 7.5, 25C, mutant R167K
41
0.0022
L-glutamate
P74515
pH 7.5, 25C, mutant R248K
41
0.0083
L-glutamate
P74515
pH 7.5, 25C, mutant H121A
41
0.0224
L-glutamate
P74515
pH 7.5, 25C, mutant T117S
41
0.16
L-glutamate
P74515
pH 7.5, 25C, mutant H121Q
41
0.367
L-glutamate
P74515
pH 7.5, 25C, wild-type enzyme
41
4.3
L-glutamate
-
pH 8.0, 25C, wild-type enzyme, in presence of DTT
41
4.5
L-glutamate
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S, in presence of DTT
41
6.9
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/S372C/S395Y
41
7.4
L-glutamate
-
pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/C372S/S395W; pH 8.0, 25C, mutant C106S/C164S/C205S/C223S/C357S/C372S/C395S/C433S/C439S/R374Q/V375F
41
8.1
L-glutamate
-
pH 8.0, 25C, wild-type enzyme
41
8.5
L-glutamate
-
pH 8.0, 25C, mutant C106S,C164S,C205S,C223S,C357S,C433S,C439S
41
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0089
(2S)-2-amino-4-[(2R,S)-2-carboxy-3-hydroxypropyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
9.2
(2S)-2-amino-4-[(2R,S)-2-carboxy-3-phenylpropyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
0.0000099
(2S)-2-amino-4-[(2R,S)-2-carboxybutyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
0.00059
(2S)-2-amino-4-[(2R,S)-2-carboxybutyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
0.023
(2S)-2-amino-4-[(2R,S)-2-carboxyhexyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
3.9
(2S)-2-amino-4-[(2R,S)-2-carboxyoctyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
0.0014
(2S)-2-amino-4-[(2R,S)-2-carboxypropyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
0.053
(2S)-2-amino-4-[2-carboxyethyl-(R,S)-sulfonimidoyl]butanoic acid
-
pH 7.5, 37C
2.5
4-methylene-L-glutamate
P19468, P48508
-
7.75
5-Chloro-4-oxo-L-norvaline
P19468, P48508
-
0.06
buthionine sulfone
P19468, P48508
-
1.2
buthionine sulfoximine
-
pH 7.0, 25C, mutant DELTA85
0.0039
cystamine
Q9NFN6
pH 8.0, 37C
11
cystamine
-
pH 7.0, 25C, mutant DELTA85
7.6
gamma-glutamylcysteine
-
pH 8.4, 37C, mutant enzyme Y464stop
13.7
gamma-glutamylcysteine
-
pH 8.4, 37C, mutant enzyme D520stop
23
gamma-glutamylcysteine
-
pH 8.4, 37C, mutant enzyme R508stop
24.3
gamma-glutamylcysteine
-
pH 8.4, 37C, mutant enzyme E494stop
2.12
gamma-L-Glu-L-Cys
-
wild-type, pH 8.0
0.72
glutathione
-
pH 7.0, 25C, versus glutamate, mutant DELTA85
1.53
glutathione
-
pH 8.2
2.21
glutathione
-
pH 7.0, 25C, versus cysteine, mutant DELTA85
6.5
glutathione
-
-
13.6
glutathione
-
; 25C, pH 8.2
0.11
GSH
-
-
0.3
GSH
-
Kis, 37C, pH 7.2, catalytic subunit GCLC, versus L-glutamate
0.4
GSH
-
Kii, 37C, pH 7.2, catalytic subunit GCLC, versus ATP
0.42
GSH
-
-
0.45
GSH
-
wild-type enzyme, pH 8.0, 37C
0.8
GSH
-
Kii, 37C, pH 7.2, catalytic subunit GCLC, versus L-glutamate; Kis, 37C, pH 7.2, holoenzyme, versus L-glutamate
1
GSH
P48506, P48507
heavy subunit
1.1
GSH
Q26820
-
1.1
GSH
-
wild-type enzyme, pH 8.0, 37C
1.3
GSH
-
Kis, 37C, pH 7.2, catalytic subunit GCLC, versus ATP
1.8
GSH
P19468, P48508
heavy subunit; heavy subunit, the Ki for GSH is tissue-dependent
1.8
GSH
-
catalytic subunit
2
GSH
P0A6W9
about, strain B
2.2
GSH
-
recombinant holoenzyme, pH 8.0, 37C
2.3
GSH
P19468, P48508
; the Ki for GSH is tissue-dependent
3.1
GSH
-
-
3.1
GSH
-
Kii, 37C, pH 7.2, holoenzyme, versus L-glutamate
3.3
GSH
P48506, P48507
holoenzyme
3.3
GSH
-
pH 8.2, 37C
3.9
GSH
-
Kii, 37C, pH 7.2, holoenzyme, versus ATP
4
GSH
P0A6W9
about, strain KM
6.5
GSH
-
Kis, 37C, pH 7.2, holoenzyme, versus ATP
8.2
GSH
-
pH 8.2, 37C
8.2
GSH
-
holoenzyme
12.9
GSH
-
pH 8.4, 37C, mutant enzyme Y464stop
18.2
GSH
-
pH 8.4, 37C, mutant enzyme E494stop
25.5
GSH
-
recombinant catalytic subunit, pH 8.0, 37C
36
GSH
-
mutant R179A, pH 8.0, 37C
277
GSH
-
pH 8.4, 37C, mutant enzyme R508stop
312
GSH
-
pH 8.4, 37C, mutant enzyme D520stop
1000
GSH
-
above, mutant R127C, pH 8.0, 37C
29.3
L-buthionine sulfoximine
-
-
0.00013
L-buthionine-R,S-sulfoximine
Q9NFN6
pH 8.0, 37C
0.15
L-buthionine-R-sulfoximine
P19468, P48508
-
0.1
L-buthionine-S-sulfoximine
-
about, pH 8.2, 37C
4.9
L-buthionine-S-sulfoximine
-
-
0.049
L-buthionine-SR-sulfoximine
-
pH 7.5, 37C
3.93
L-Glu
-
mutant C266S, pH 8.0
12.5
ophthalmic acid
P19468, P48508
noncompetitive
2.7
S-sulfo-homocysteine
P19468, P48508
-
4.7
L-Glu
-
mutant C266A, pH 8.0
additional information
additional information
P19468, P48508
the Ki for GSH is tissue-dependent
-
additional information
additional information
-
inhibition kinetics
-
additional information
additional information
P0A6W9
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
33.7
buthionine sulfoxime
P74515
pH 7.5, 25C, recombinant enzyme
-
7.9
buthionine sulfoximine
-
-
10.8
buthionine sulfoximine
-
-
11.5
buthionine sulfoximine
Q1W2L8
-
1.2
DTT
-
wild-type enzyme
5.1
DTT
Q1W2L8
-
5.5
DTT
-
mutant C356A enzyme
3.8
glutathione
-
mutant C356A enzyme
4.1
glutathione
Q1W2L8
-
5.5
glutathione
-
wild-type enzyme
6.4
glutathione
-
-
7.4
glutathione
P74515
pH 7.5, 25C, recombinant enzyme
8.1
glutathione
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.001
P48506, P48507
native COS cells
0.0027
-
lung extract exposed to air
0.0041
-
lung extract exposed to cadmium aerosol with 3.3 mg Cd/m3
0.0048
-
lung extract exposed to cadmium aerosol with 4.2 mg Cd/m3
0.0097
-
partially purified enzyme from astrocytes
0.014
P48506, P48507
transformed COS cells expressing both the recombinant subunits at equal amounts
0.031
-
recombinant wild-type enzyme
0.038
P48506, P48507
transformed COS cells expressing the recombinant catalytic subunit
0.05
-
recombinant mutant S495T
0.051
-
recombinant mutant A494V and mutant A494L
0.12
-
purified recombinant mutant C249G catalytic subunit and mutant C295G catalytic subunit
0.17
-
purified recombinant mutant C52G catalytic subunit and mutant C248G catalytic subunit
0.38
-
purified recombinant mutant C605G catalytic subunit
0.44
-
purified mutant R127C enzyme, substrates L-glutamate and L-alpha-aminobutyrate
0.48
-
purified recombinant mutant C501G catalytic subunit
0.63
-
purified recombinant mutant C491G catalytic subunit
0.92
-
purified recombinant mutant C553G catalytic subunit
1.15
-
recombinant catalytic subunit
1.15
-
purified recombinant wild-type catalytic subunit
1.83
-
purified recombinant mutant C553G holoenzyme
4.67
-
purified recombinant mutant C249G holoenzyme
5.17
-
purified recombinant mutant C605G holoenzyme
5.33
-
purified recombinant mutant C295G holoenzyme
5.67
-
purified recombinant mutant C248G holoenzyme
6.17
-
recombinant holoenzyme
6.17
-
purified recombinant wild-type holoenzyme
6.67
-
purified recombinant mutant C52G holoenzyme
7
-
purified recombinant mutants C491G holoenzyme and C501G holoenzyme
8.39
-
Drosophila catalytic subunit as a hybrid with the wild-type human modifier subunit, substrate L-alpha-aminobutyrate
8.45
-
wild-type holoenzyme
8.86
-
purified wild-type enzyme, substrates L-glutamate and L-alpha-aminobutyrate
14.5
-
liver enzyme
19.2
-
kidney enzyme
25
P48506, P48507
purified recombinant enzyme
25
P19468, P48508
purified enzyme
25
-
above, purified recombinant holoenzyme
28.75
-
-
39.5
-
pH 8.2
51
P0A6W9
purified enzyme
additional information
-
-
additional information
-
-
additional information
-
-
additional information
P19468, P48508
-
additional information
-
the activity of both the recombinant holoenzyme and catalytic subunit increased by 40% after removal of the His-tag
additional information
-
GSH and GSSG levels in cells after treatment with pyrrolidine dithiocarbamate
additional information
-
-
additional information
P48506
kinetic measurement, based on an HPLCESI-MS technique: L-2-aminobutyrate is used instead of cysteine as triggering substrate with saturating concentrations of glutamate and ATP, and the gamma-glutamylaminobutyrate formed is measured at m /z = 233 at regular time intervals. The reaction rate is maximum because ATP is held constant by enzymatic recycling of ADP by pyruvate kinase and phosphoenolpyruvate
additional information
-
kinetic measurement, based on an HPLCESI-MS technique: L-2-aminobutyrate is used instead of cysteine as triggering substrate with saturating concentrations of glutamate and ATP, and the gamma-glutamylaminobutyrate formed is measured at m /z = 233 at regular time intervals. The reaction rate is maximum because ATP is held constant by enzymatic recycling of ADP by pyruvate kinase and phosphoenolpyruvate
additional information
-
correlation between enzyme activity and genotype in black and white individuals, overview
additional information
P19468
0.13 microg phosphate/mg protein, measured in tumor tissue after treatment with dietary glutamine; 0.2 microg phosphate/mg protein, measured in tumor tissue; about 0.35 mmicrog phosphate/mg protein, measured in jejunal mucosa in normal rats and DMBA-treated rats with and without tumors; about 0.43 microg phosphate/mg protein, measured in jejunal mucosa after treatment with dietary glutamine in normal rats and in DMBA-treated rats with and without tumor
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
-
assay at
7.5
-
assay at
7.5
Q9W3K5
in presence of NADPH
7.5
P74515
assay at
8
-
assay at
8
-
assay at
8
-
assay at
8
-
assay at
8
Q9NFN6
assay at
8
-
assay at
8.2 - 8.3
B4YE15
assay at
8.2
-
assay at
8.2
P0A6W9
assay at
8.2
Q9W3K5
in absence of NADPH
8.2
-
assay at
8.6
P48506
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9
-
50% of maximal activity at pH 7.0 and pH 9.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
B4YE15
assay at
25
-
assay at
25
P74515
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
P0A6W9
assay at
37
-
assay at
37
Q9NFN6
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
A2780/100 ovarian carcinoma cell exhibits resistance to DNA crosslinking agents, chlorambucil, cisplatin, melphalan, and ionizing radiation compared to the parental cell line, A2780. Drug-resistant cells have the inherent ability to maintain increased gamma-GCS activity
Manually annotated by BRENDA team
-
corners of, highest enyzme content
Manually annotated by BRENDA team
-
primary cell culture
Manually annotated by BRENDA team
-
primary astrocyte
Manually annotated by BRENDA team
P48506, P48507
malignant cell line
Manually annotated by BRENDA team
-
treatment of human breast cancer cells with 2-deoxy-D-glucose causes metabolic oxidative stress that is accompanied by increases in steady-state levels of glutamate cysteine ligase mRNA, glutamate cysteine ligase activity and glutathione content
Manually annotated by BRENDA team
-
bronchial epithelial cells
Manually annotated by BRENDA team
-
interscapular brown adipose tissue
Manually annotated by BRENDA team
-
oligophosphopeptides derived from egg yolk phosvitin up-regulate gamma-glutamylcysteine synthetase and antioxidant enzymes against oxidative stress in Caco-2 cells
Manually annotated by BRENDA team
-
astrocyte, primary
Manually annotated by BRENDA team
-
acoustic overstimulation facilitates the expression of glutamate-cysteine ligase catalytic subunit probably through enhanced DNA binding of activator protein-1 and/or NF-kappaB in the murine cochlea
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
basal expression of glutamate-cysteine ligase catalytic subunit and regulatory subunit is 59fold and 25fold higher in visceral yolk sac, respectively, compared to the embryo
Manually annotated by BRENDA team
-
alveolar, higher content compared to the lung parenchyma
Manually annotated by BRENDA team
-
bronchial epithelial cells
Manually annotated by BRENDA team
-
normal and low-GSH sheep erythrocytes
Manually annotated by BRENDA team
-
immortalized bronchial epithelial cells from a healthy individual
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
auditory cell
Manually annotated by BRENDA team
-
hepatocarcinoma cell line
Manually annotated by BRENDA team
-
primary cell culture
Manually annotated by BRENDA team
-
oncogene MYCN-amplified cells
Manually annotated by BRENDA team
Q8W4W3
under optimal conditions found in bundle sheath and mesophyll cells, chilling stress strongly induces gamma-ECS mRNA
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
male transgenic mice induced to overexpress glutamate-cysteine ligase exhibit resistance to acetaminophen-induced liver injury when compared with acetaminophen-treated male mice carrying, but not expressing glutamate-cysteine ligase transgenes, or to female glutamatecysteine ligase transgenic mice
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
both subunits of gamma-GCS are most prominently expressed in bronchiolar epithelium and are expressed generally weakly in alveolar macrophages. In interstitial lung diseases, gamma-GCS is expressed especially in the alveolar and metaplastic alveolar epithelium but is low in the fibrotic areas. The regulation of gamma-GCS is complex, being differentially modulated by various cytokines and durations of exposure, and in various cell types in human lung. Potential mechanism for the low gamma-GCS levels in fibrotic lung diseases may include down-regulation of catalytically active subunit of gamma-GCS
Manually annotated by BRENDA team
-
primary cortical neuron
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
lower content compared to the alveolar epithelium
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
catalytic subunit GCLc and modifier subunit GCLm are differently regulated during development in the placenta and the yolk sac. GCLm mRNA is constant throughout development, GCLc mRNA increases at gd 18 in both the placenta and the yolk sac. In the placenta the increase is localized to the spongiotrophoblast layer. GCLc protein level does not increase in parallel with the mRNA. The localization of GCLc mRNA and protein in mouse placenta is different, with the mRNA concentrated in the spongiotrophoblast and the protein in the labyrinth
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
upregulation of gamma-glutamate-cysteine ligase is part of the long-term adaptation process to iron accumulation in neuronal SH-SY5Y cells
Manually annotated by BRENDA team
-
oncogene MYCN-non-amplified cells
Manually annotated by BRENDA team
-
the shoot-specific expression of gamma-glutamylcysteine synthetase directs the long-distance transport of thiol-peptides to roots conferring tolerance to mercury and arsenic
Manually annotated by BRENDA team
-
oncogene MYCN-amplified cells
Manually annotated by BRENDA team
-
oncogene MYCN-non-amplified cells
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
P48506, P48507
-
Manually annotated by BRENDA team
-
catalytic subunit GCLc andmodifier subunit GCLm are differently regulated during development in the placenta and the yolk sac. GCLm mRNA is constant throughout development, GCLc mRNA increases at gd 18 in both the placenta and the yolk sac
Manually annotated by BRENDA team
-
gamma-glutamylcysteine synthetase mediates the c-Myc-dependent response to antineoplastic agents in melanoma cells
Manually annotated by BRENDA team
additional information
-
correlating regional-specific expression and activity pattern, levels of heavy and light subunit are similar, distribution in brain
Manually annotated by BRENDA team
additional information
P48506, P48507
expression patterns of both subunits in the tissues, overview, 2 transcript different in size for both the heavy and light subunit occur in the tissues, some tumors overexpress only the heavy subunit rather than the holoenzyme
Manually annotated by BRENDA team
additional information
P48506, P48507
expression patterns of both subunits in the tissues, overview, 2 transcripts different in size for both the heavy and light subunit occur in the tissues, some tumors overexpress only the heavy subunit rather than the holoenzyme
Manually annotated by BRENDA team
additional information
-
genotyping of 60 tumor cell lines from diverse source tissues for the GLCLC trinuleotide repeat
Manually annotated by BRENDA team
additional information
-
pulmonary distribution
Manually annotated by BRENDA team
additional information
-
in most tissues the modifier subunit GCLM is limiting, suggesting that an increase in GCLM alone would increase gamma-glutamylcysteine synthesis
Manually annotated by BRENDA team
additional information
B4YE15
seasonal variations of activity in the digestive gland and to a lesser extent in the gills occur with activity increasing in spring compared to winter, no sex differences
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
P48506, P48507
exclusively
Manually annotated by BRENDA team
P19468, P48508
exclusively
Manually annotated by BRENDA team
P97494, Q97SC0
exclusively
Manually annotated by BRENDA team
additional information
-
while GCLC and GCLM are generally considered to be cytosolic proteins there is evidence that they may exhibit altered subcellular localization in certain circumstances
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Pasteurella multocida (strain Pm70)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Streptococcus agalactiae serotype V (strain ATCC BAA-611 / 2603 V/R)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
P74515
recombinant enzyme, gel filtration
726912
55000
-
gel filtration
1120
56000
-
gel filtration, native PAGE
1118
60000 - 65000
-
recombinant full-length enzyme, gel filtration
662247
60000
-
gel filtration
1149
62000 - 64000
-
gel filtration, ultracentrifugal analysis, SDS-PAGE after cross-linking with dimethylsuberimidate
1126
70000
-
gel filtration, a 100000 MW enzyme form is also detected
1140
70000
-
bifunctional enzyme accounts for gamma-glutamylcysteine synthetase and glutathione synthetase activities, gel filtration
662339
78000
-
gel filtration
1128
78200
-
-
651393
80000
D7P1H2
SDS-PAGE
706151
100000
-
gel filtration, a 70000 MW enzyme form is also detected
1140
100000
P19468, P48508
kidney enzyme, native PAGE
649263
104000
-
-
1122
114000
-
recombinant holoenzyme, gel filtration
649413
114000
-
recombinant wild-type and mutant holoenzymes, gel filtration
649655
120000
-
PAGE
706061
140000
-
holoenzyme, gel filtration
652480
191000
-
bifunctional enzyme gamma-glutamate-cysteine ligase-glutathione synthetase, gel filtration
662457
220000
-
gel filtration
662457
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 73000, SDS-PAGE
?
-
x * 70000, SDS-PAGE
?
-
x * 72000 + x * 32000, denaturing SDS-PAGE
?
-
x * 30548, calculation from nucleotide sequence
?
-
unlike kidney enzyme, most of liver enzyme is in a reduced form which does not have disulfide linkage between heavy and light chain
?
-
x * 73000, calculation from nucleotide sequence
?
-
x * 45000, SDS-PAGE
?
Q56277
x * 49300, catalytic subunit
?
Q09768
x * 71400, catalytic subunit
?
Q9NFN6
x * 74200, amino acid sequence calculation
?
-
x * 78300, catalytic subunit
dimer
-
-
dimer
-
2 * 85000, SDS-PAGE
dimer
-
2 * 60000, SDS-PAGE
dimer
-
1 * 75000 + 1 * 25000, denaturing PAGE in presence of 50 mM DTT
dimer
-
1 * 75000 + 1 * 25000, nondenaturing PAGE in presence of 50 mM DTT
dimer
-
2 * 34000, SDS-PAGE
dimer
-
1 * 74000 + 1 * 24000, SDS-PAGE. One enzyme species of MW 100000 Da detected by SDS-PAGE after cross-linking with dimethylsuberimidate
dimer
-
1 * 73000 + 1 * 27700, PAGE in presence of 50 mM DTT
dimer
-
2 * 34000
dimer
P19468, P48508
1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE
dimer
P97494, Q97SC0
1 * 72700, heavy catalytic subunit, + 1 * 30500, light regulatory subunit, SDS-PAGE
dimer
P48506, P48507
1 * 72800, heavy catalytic subunit, + 1 * 30700, light regulatory subunit, SDS-PAGE
dimer
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE
dimer
-
1 * 73000, about, heavy catalytic subunit, + 1 * 31000, about, light regulatory subunit, SDS-PAGE
dimer
-
1 * 80000, about, catalytic subunit, + 1 * 28000, about, modifier subunit, SDS-PAGE
dimer
-
2 * 75000, recombinant wild-type and mutant enzymes, SDS-PAGE
dimer
-
heavy and light subunit
dimer
-
heavy and light subunit
dimer
-
heterodimer of a catalytic subunit and a regulatory subunit, encoded by 2 genes
dimer
-
glutamatecysteine ligase is a heterodimer of a GCLC (GCL catalytic subunit) that possesses all of the enzymatic activity and a GCLM (GCL modifier subunit) that alters the Ki of GCLC for GSH. Differential regulation of glutamatecysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation
dimer
-
2 *85000, SDS-PAGE
dimer
-
heterodimer, comprising a catalytic subunit (GCLC) and a regulatory subunit (GCLM). GCLC alone can catalyze the formation of L-gamma-glutamyl-L-cysteine, its binding with GCLM enhances the enzyme activity by lowering the Km for glutamate and ATP, and increasing the Ki for GSH inhibition
dimer
-
1 * 73000, about, GCLC, + 1 * 31000, about, GCLM
dimer
-
GCL is composed of catalytic GCLC and modifier GCLM subunits
dimer
-
GCL reveals two redox-sensitive intramolecular disulfide bonds, CC1 and CC2, located at the homodimer interface that regulate plant GCL activity
dimer
-
heterodimer consisting of catalytic and modifier subunits GCLC and GCLM
dimer
-
heterodimer consisting of subunits GCLC and GCLM
dimer
-
the enzyme consists of a catalytic subunit GCLC and a modifier subunit GCLM
dimer
Q1W2L8
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, amino acids contributing to the homodimer interface in GCL are highly conserved among plant GCLs, but not in related proteobacterial GCLs. NtGCL forms a homodimer under oxidizing conditions
dimer
-
1 * 66000 + 1 * 57000, SDS-PAGE
heterodimer
-
glutamate-cysteine ligase consists of a catalytic subunit (GCLC) and a modifier subunit (GCLM)
monomer
-
1 * 56000, SDS-PAGE
monomer
-
1 * 55000, SDS-PAGE
monomer
P0A6W9
1 * 58200
monomer
-
1 * 59900, catalytic unit
monomer
-
1 * 60000, about
monomer
Q26820
1 * 77500, catalytic unit
monomer
P90557
1 * 78100, catalytic unit
monomer
-
1 * 78200
monomer
-
x * 35000, mutant enzyme modifier subunit, SDS-PAGE
monomer
-
bifunctional enzyme accounts for gamma-glutamylcysteine synthetase and glutathione synthetase activities
monomer
-
proteobacterial GCLs remain monomeric under oxidizing and reducing conditions, overview
monomer
P74515
1 * 46000, recombinant enzyme, SDS-PAGE
additional information
-
the light subunit has a regulatory function affecting the affinity for Glu and GSH
additional information
-
the heavy subunit contains all of the structural requirements for enzymatic activity and also for feedback inhibition by glutathione
additional information
-
quarternary structure
additional information
P97494, Q97SC0
quarternary structure
additional information
-
enzyme consists of 2 subunits, the heavy catalytic one and the light regulatory one
additional information
-
enzyme consists of a catalytic GCLC and a modulatory GCLM subunit
additional information
-
enzyme is build of 2 subunits, a modifier and a catalytic subunit, the modifier subunit DmGCLM possesses cysteine residues, Cyys213, Cys214, and Cys267, which can form covalent interactions with the catalytic subunit DmGCLC and modify its activity, the activity of the holoenzyme is enhanced compared to the catalytic subunit alone
additional information
P19468, P48508
quarternary structure, the heavy subunit monomer may be essentially nonfunctional under physiological conditions
additional information
P48506, P48507
quarternary structure, the heavy subunit monomer may be essentially nonfunctional under physiological conditions
additional information
-
quaternary structure
additional information
P97494, Q97SC0
quaternary structure
additional information
-
reaction can be performed by the catalytic subunit alone, but presence of the regulatory subunit in the holoenzyme increases the activity
additional information
-
reaction can be performed by the catalytic subunit alone, but presence of the regulatory subunit in the holoenzyme increases the activity and the specificity with L-2-aminobutyrate as substrate
additional information
-
structure modeling
additional information
-
the dimeric enzyme is composed of a heavy, catalytic subunit and a light, regulatory subunit
additional information
-
the holoenzyme consists of a heavy catalytic and a light modifier subunit, i.e. gamma-GCSH and gamma-GCSL, protein modeling
additional information
-
the holoenzyme consists of a heavy catalytic and a light regulatory subunit, i.e. gamma-GCSh and gamma-GCSl
additional information
Q26820
the recombinant heavy subunit contains a 55 kDa insert which may function as the small subunit
additional information
P90557
the recombinant heavy subunit contains a 55 kDa insert which may function as the small subunit
additional information
-
reaction is catalyzed by the catalytic subunit GCLC or by the holoenzyme (GCLholo), which comprises GCLC and the modifier subunit GCLM. GCLM decreases the Km for ATP by about 6fold and decreases the Km-value for glutamate and increases the Ki-value for feedback inhibition by GSH. GCLM increases by 4.4fold the turnover number for gamma-glutamylcysteine synthesis
additional information
-
GCL is a heterodimeric protein composed of catalytic GCLC and modifier GCLM subunits that are expressed from different genes, the catalytic subunit GCLC contains the active site responsible for the ATP-dependent bond formation between the amino group of cysteine and the gamma-carboxyl group of glutamate, the modifier subunit GCLM through direct interaction with GCLC acts to increase the catalytic efficiency of GCLC. GCL subunit protein structures, overview. GCLM is quite sensitive to aggregation in vitro in the absence of GCLC
additional information
-
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, which both strongly impact on GCL activity in vitro, cysteines of CC2 involved in the monomer-dimer transition in GCL. Amino acids contributing to the homodimer interface in BjGCL are highly conserved among plant GCLs, but not in related proteobacterial GCLs
additional information
-
upon oxidative stress, activation of GCL occurrs within min of treatment and without any change in GCL protein levels, and coincides with an increase in the proportion of GCL catalytic subunit in the holoenzyme form. Likewise, GCL modifier subunit shifts from the monomeric form to holoenzyme and higher molecular weight species. Neither GCL activation, nor the formation of holoenzyme, requires a covalent intermolecular disulfide bridge between GCL catalytic subunit and GCL modifier subunit
additional information
-
the enzyme consists of a catalytic (GCLC) and a modifier (GCLM) subunit
additional information
Rattus norvegicus Sprague-Dawley
-
the enzyme consists of a catalytic (GCLC) and a modifier (GCLM) subunit
-
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
Q9W3K5
the enzyme exists in vivo as a mixture of phosphorylated and dephosphorylated forms
phosphoprotein
-
phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII
proteolytic modification
-
caspase-mediated cleavage of GCLC, overview
phosphoprotein
P97494
the enzyme exists in vivo as a mixture of phosphorylated and dephosphorylated forms
phosphoprotein
-
phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII
proteolytic modification
-
caspase-mediated cleavage of GCLC, overview
phosphoprotein
P19468, P48508
the heavy, catalytic subunit can be phosphorylated by dibutyrl cAMP in hepatocytes, and by protein kinase C, protein kinase A, and Ca2+/calmodulin-dpendent kinas II on serine and threonine residues in presence of Mg2+, regulatory role of dephosphorylation/phosphorylation in vivo
phosphoprotein
-
phosphorylation plays an important role in regulating GCL activity in vivo, phosphorylation of GCLC occurs on serine and threonine residues in vitro and the phosphorylation sites are likely identical for all three kinases protein kinase C, PKC, cAMP-dependent protein kinase, PKA, or Ca2+-calmodulin-dependent protein kinase II, CMKII
proteolytic modification
-
caspase-mediated cleavage of GCLC, overview
lipoprotein
-
myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview
additional information
-
post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity
lipoprotein
-
myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview
additional information
-
post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity
additional information
-
4-hydroxy-2-nonenal alters GCL holoenzyme formation and activity via direct posttranslational modification of the GCL subunits in vitro. 4-Hydroxy-2-nonenal directly modifies Cys553 of catalytic subunit GCLC and Cys35 of modulatory subunit GCLM in vitro, which significantly increases monomeric GCLC enzymatic activity, but reduces GCL holoenzyme activity and formation of the GCL holoenzymecomplex
lipoprotein
-
myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview
additional information
-
post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, crystal structure at 2.1 A resolution
-
22.6 mg/ml purified enzyme, wild-type or mutant, hanging drop vapour diffusion method, equal volume of protein and reservoir solution, reservoir solution: 3.9 M sodium formate, pH 7.4, equilibration with reservoir solution at 293K, X-ray diffraction structure determination and analysis at 2.8 A resolution
-
sitting-drop vapor diffusion method, crystal structure of unliganded enzyme and enzyme complexed with a sulfoximine-based transition-state analog inhibitor at resolutions of 2.5 and 2.1 A, respectively. In the crystal structure of the complex, the bound inhibitor is phosphorylated at the sulfoximido nitrogen and is coordinated to three Mg2+ ions
-
homology model of the catalytic subunit of human glutamate cysteine ligase. Examination of the model suggests that post-translational modifications of cysteine residues may be involved in the regulation of enzymatic activity
-
structure of the GCL-glutathione complex to 2.5 A resolution indicates that the inhibitor occupies both the glutamate- and the presumed cysteine-binding site and disrupts the previously observed Mg2+-coordination in the ATP-binding site. The structure of the complex with mechanism-based inhibitor L-buthionine-S-sulfoximine to 2.2 A resolution confirms that L-buthionine-S-sulfoximine is phosphorylated on the sulfoximine nitrogen to generate the inhibitory species and reveals contacts that likely contribute to transition state stabilization
-
structures of glutamate cysteine ligase in the presence of glutamate and MgCl2, to 2.1 A resolution, and in complex with glutamate, MgCl2, and ADP to 2.7 A resolution. Structures reveal an unusual binding pocket for the alpha-carboxylate of the glutamate substrate and an ATP-independent Mg2+ coordination site, clarifying the Mg2+-dependence of the enzymatic reaction
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 9
-
10 min stable
1126
7
-
55C, 35 min, 50% loss of activity
1120
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0 - 35
-
10 min, stable
1126
40
-
15 min, stable
1140
45
-
5 min, 70% loss of activity
1140
55
-
pH 7.0, 35 min, 50% loss of activity
1120
56
-
total loss of activity
1140
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme is inactivated by freezing
-
activity of the holoenzyme and of the catalytic subunit is reduced by 20% and 10%, respectively, after 1 cycle of freezing and thawing
-
enzyme is inactivated by freezing
P48506, P48507
freezing of the purified recombinant enzyme in solution results in irreversible inactivation
-
glycerol is required for enzyme stability during storage
P48506, P48507
glycerol stabilizes
-
L-glutamate stabilizes the enzyme during purification,
P48506, P48507
Mn2+ destabilizes the enzyme during purification
P48506, P48507
enzyme is inactivated by freezing
P97494, Q97SC0
inactivated by freezing
P97494, Q97SC0
freezing, -20C, and thawing results in 70-80% loss of activity
-
enzyme is inactivated by freezing
-
easy loss of activity on freezing at -20C
-
enzyme is inactivated by freezing
-
optimal stabilization in presence of 10 mM Mg2+, 24% loss of activity after 12 h at 4C without Mg2+. Mn2+ has no effect on stability
-
enzyme is inactivated by freezing
P19468, P48508
glycerol is required for enzy