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ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
ir
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
additional information
?
-
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
first step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
rate-limiting enzyme in the glutathione biosynthesis pathway
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
rate-limiting enzyme in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
GCL-mediated phosphorylation of L-glutamate creating the activated enzyme-bound gamma-glutamylphosphate intermediate
-
-
?
additional information
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
-
rate-limiting enzyme in GSH biosynthesis
-
-
?
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
?
-
-
post-translational regulation of GCL, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
additional information
?
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
first step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
rate-limiting enzyme in the glutathione biosynthesis pathway
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
rate-limiting enzyme in glutathione biosynthesis
-
-
?
additional information
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
-
rate-limiting enzyme in GSH biosynthesis
-
-
?
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
?
-
-
post-translational regulation of GCL, overview
-
-
?
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dimer
1 * 72700, heavy catalytic subunit, + 1 * 30500, light regulatory subunit, SDS-PAGE
?
-
x * 73000, calculation from nucleotide sequence
dimer
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, 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
-
heterodimer consisting of catalytic and modifier subunits GCLC and GCLM
heterodimer
-
glutamate-cysteine ligase consists of a catalytic subunit (GCLC) and a modifier subunit (GCLM)
heterodimer
glutamate-cysteine ligase (GCL) is a heterodimer enzyme composed of a catalytic subunit (GCLC) and a modulator subunit (GCLM)
additional information
quarternary structure
additional information
quarternary structure
additional information
quaternary structure
additional information
quaternary structure
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 regulatory subunit, i.e. gamma-GCSh and gamma-GCSl
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
-
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 consists of a catalytic (GCLC) and a modifier (GCLM) subunit
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Reid, L.L.; Botta, D.; Lu, Y.; Gallagher, E.P.; Kavanagh, T.J.
Molecular cloning and sequencing of the cDNA encoding the catalytic subunit of mouse glutamate-cysteine ligase
Biochim. Biophys. Acta
1352
233-237
1997
Mus musculus
brenda
Griffith, O.W.; Mulcahy, R.T.
The enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase
Adv. Enzymol. Relat. Areas Mol. Biol.
73
209-267
1999
Ascaris suum, Bos taurus, [Candida] boidinii, Ovis aries, Nicotiana tabacum, no activity in Entamoeba histolytica, Proteus mirabilis, Sus scrofa, Xenopus sp., no activity in Giardia sp., Mus musculus (A0A0H2UNM8), Mus musculus (P97494), Escherichia coli (P0A6W9), Rattus norvegicus (P19468), Rattus norvegicus (P48508), Saccharomyces cerevisiae (P32477), Arabidopsis thaliana (P46309), Homo sapiens (P48506), Homo sapiens (P48507), Homo sapiens, Leishmania tarentolae (P90557), Schizosaccharomyces pombe (Q09768), Trypanosoma brucei (Q26820), Acidithiobacillus ferrooxidans (Q56277)
brenda
Wild, A.C.; Mulcahy, R.T.
Regulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defenses
Free Radic. Res.
32
281-301
2000
Saccharomyces cerevisiae, Homo sapiens, Mus musculus, Rattus norvegicus
brenda
Kang, Y.; Viswanath, V.; Jha, N.; Qiao, X.; Mo, J.Q.; Andersen, J.K.
Brain gamma-glutamyl cysteine synthetase (GCS) mRNA expression patterns correlate with regional-specific enzyme activities and glutathione levels
J. Neurosci. Res.
58
436-441
1999
Mus musculus
brenda
Toroser, D.; Sohal, R.S.
Kinetic characteristics of native gamma-glutamylcysteine ligase in the aging housefly, Musca domestica L
Biochem. Biophys. Res. Commun.
326
586-593
2005
Mus musculus
brenda
Botta, D.; Franklin, C.C.; White, C.C.; Krejsa, C.M.; Dabrowski, M.J.; Pierce, R.H.; Fausto, N.; Kavanagh, T.J.
Glutamate-cysteine ligase attenuates TNF-induced mitochondrial injury and apoptosis
Free Radic. Biol. Med.
37
632-642
2004
Mus musculus
brenda
Chen, Y.; Shertzer, H.G.; Schneider, S.N.; Nebert, D.W.; Dalton, T.P.
Glutamate cysteine ligase catalysis: dependence on ATP and modifier subunit for regulation of tissue glutathione levels
J. Biol. Chem.
280
33766-33774
2005
Mus musculus
brenda
Diaz, D.; Krejsa, C.M.; White, C.C.; Charleston, J.S.; Kavanagh, T.J.
Effect of methylmercury on glutamate-cysteine ligase expression in the placenta and yolk sac during mouse development
Reprod. Toxicol.
19
117-129
2004
Mus musculus
brenda
Yang, Y.; Chen, Y.; Johansson, E.; Schneider, S.N.; Shertzer, H.G.; Nebert, D.W.; Dalton, T.P.
Interaction between the catalytic and modifier subunits of glutamate-cysteine ligase
Biochem. Pharmacol.
74
372-381
2007
Mus musculus
brenda
Toroser, D.; Yarian, C.S.; Orr, W.C.; Sohal, R.S.
Mechanisms of gamma-glutamylcysteine ligase regulation
Biochim. Biophys. Acta
1760
233-244
2006
Mus musculus (P97494), Mus musculus, Drosophila melanogaster (Q9W3K5), Drosophila melanogaster
brenda
Botta, D.; Shi, S.; White, C.C.; Dabrowski, M.J.; Keener, C.L.; Srinouanprachanh, S.L.; Farin, F.M.; Ware, C.B.; Ladiges, W.C.; Pierce, R.H.; Fausto, N.; Kavanagh, T.J.
Acetaminophen-induced liver injury is attenuated in male glutamate-cysteine ligase transgenic mice
J. Biol. Chem.
281
28865-28875
2006
Mus musculus
brenda
Nagashima, R.; Sugiyama, C.; Yoneyama, M.; Kuramoto, N.; Kawada, K.; Ogita, K.
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
Neurochem. Int.
51
209-215
2007
Mus musculus
brenda
Bea, F.; Hudson, F.N.; Neff-Laford, H.; White, C.C.; Kavanagh, T.J.; Kreuzer, J.; Preusch, M.R.; Blessing, E.; Katus, H.A.; Rosenfeld, M.E.
Homocysteine stimulates antioxidant response element-mediated expression of glutamate-cysteine ligase in mouse macrophages
Atherosclerosis
203
105-111
2008
Mus musculus
brenda
Botta, D.; White, C.C.; Vliet-Gregg, P.; Mohar, I.; Shi, S.; McGrath, M.B.; McConnachie, L.A.; Kavanagh, T.J.
Modulating GSH synthesis using glutamate cysteine ligase transgenic and gene-targeted mice
Drug Metab. Rev.
40
465-477
2008
Mus musculus
brenda
Wu, H.; White, C.C.; Isanhart, J.P.; McBride, T.J.; Kavanagh, T.J.; Hooper, M.J.
Optimization and application of glutamate cysteine ligase measurement in wildlife species
Ecotoxicol. Environ. Saf.
72
572-578
2008
Anas platyrhynchos, Mus musculus, Rattus norvegicus
brenda
Franklin, C.C.; Backos, D.S.; Mohar, I.; White, C.C.; Forman, H.J.; Kavanagh, T.J.
Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase
Mol. Aspects Med.
30
86-98
2008
Arabidopsis thaliana, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
brenda
Kobayashi, T.; Watanabe, Y.; Saito, Y.; Fujioka, D.; Nakamura, T.; Obata, J.E.; Kitta, Y.; Yano, T.; Kawabata, K.; Watanabe, K.; Mishina, H.; Ito, S.; Kugiyama, K.
Mice lacking the glutamate-cysteine ligase modifier subunit are susceptible to myocardial ischaemia-reperfusion injury
Cardiovasc. Res.
85
785-795
2010
Mus musculus
brenda
Thompson, J.A.; White, C.C.; Cox, D.P.; Chan, J.Y.; Kavanagh, T.J.; Fausto, N.; Franklin, C.C.
Distinct Nrf1/2-independent mechanisms mediate As 3+-induced glutamate-cysteine ligase subunit gene expression in murine hepatocytes
Free Radic. Biol. Med.
46
1614-1625
2009
Mus musculus
brenda
Shinohara, M.; Ybanez, M.D.; Win, S.; Than, T.A.; Jain, S.; Gaarde, W.A.; Han, D.; Kaplowitz, N.
Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1
J. Biol. Chem.
285
8244-8255
2010
Mus musculus
brenda
Gao, S.S.; Choi, B.M.; Chen, X.Y.; Zhu, R.Z.; Kim, Y.; So, H.; Park, R.; Sung, M.; Kim, B.R.
Kaempferol suppresses cisplatin-induced apoptosis via inductions of heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit in HEI-OC1 cell
Pharm. Res.
27
235-245
2010
Mus musculus
brenda
Backos, D.S.; Brocker, C.N.; Franklin, C.C.
Manipulation of cellular GSH biosynthetic capacity via TAT-mediated protein transduction of wild-type or a dominant-negative mutant of glutamate cysteine ligase alters cell sensitivity to oxidant-induced cytotoxicity
Toxicol. Appl. Pharmacol.
243
35-45
2010
Mus musculus
brenda
Backos, D.S.; Fritz, K.S.; Roede, J.R.; Petersen, D.R.; Franklin, C.C.
Posttranslational modification and regulation of glutamate-cysteine ligase by the alpha,beta-unsaturated aldehyde 4-hydroxy-2-nonenal
Free Radic. Biol. Med.
50
14-26
2011
Homo sapiens, Mus musculus
brenda
Sikalidis, A.K.; Mazor, K.M.; Lee, J.I.; Roman, H.B.; Hirschberger, L.L.; Stipanuk, M.H.
Upregulation of capacity for glutathione synthesis in response to amino acid deprivation: regulation of glutamate-cysteine ligase subunits
Amino Acids
46
1285-1296
2014
Homo sapiens, Mus musculus, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Foeller, M.; Harris, I.S.; Elia, A.; John, R.; Lang, F.; Kavanagh, T.J.; Mak, T.W.
Functional significance of glutamate-cysteine ligase modifier for erythrocyte survival in vitro and in vivo
Cell Death Differ.
20
1350-1358
2013
Mus musculus
brenda
Akaboshi, T.; Yamanishi, R.
Certain carotenoids enhance the intracellular glutathione level in a murine cultured macrophage cell line by inducing glutamate-cysteine-ligase
Mol. Nutr. Food Res.
58
1291-1300
2014
Mus musculus (P97494 AND O09172), Mus musculus
brenda