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Information on EC 6.3.2.2 - glutamate-cysteine ligase and Organism(s) Rattus norvegicus and UniProt Accession P19468
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6.3.2.2 glutamate-cysteine ligaseIUBMB Comments
Can use L-aminohexanoate in place of glutamate.
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Word Map
- 6.3.2.2
-
ganglion
- retinal
- nerve
- heme
-
plexiform
- fiber
- sulfoximine
- dismutase
-
coherence
-
tomography
-
buthionine
- s-transferase
- oxygenase-1
-
macular
-
erythroid
- quinone
-
neuroprotective
-
2-related
-
amacrine
-
cytoprotective
- gssg
-
nadph:quinone
- glaucoma
-
nf-e2-related
-
acuity
- transpeptidase
-
sd-oct
-
peripapillary
-
intravitreal
-
nrf2-mediated
-
nrf2-dependent
-
dentate
-
spectral-domain
-
nrf2-are
-
factor-erythroid
-
subgranular
-
glutathione-related
-
gsh-dependent
- phytochelatins
-
l-buthionine-s,r-sulfoximine
- tert-butylhydroquinone
-
oxidoreductase-1
-
ech-associated
-
kelch-like
-
nrf2-regulated
-
fovea
- biotechnology
- medicine
-
perimetry
- synthesis
-
gsh-depleting
- agriculture
- drug development
-
etdrs
- pharmacology
-
spectralis
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
gcl, gamma-glutamylcysteine synthetase, glutamate-cysteine ligase, gamma-gcs, glutamate cysteine ligase, gamma-glutamylcysteine ligase, gamma-ecs, glclc, gammagcs, gamma-gc, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Gamma-ECS
-
-
-
-
gamma-Glutamyl-L-cysteine synthetase
-
-
-
-
gamma-Glutamylcysteine synthetase
gamma-Glutamylcysteinyl-synthetase
-
-
-
-
GCL
GCS
glutamate cysteine ligase
Synthetase, gamma-glutamylcysteine
-
-
-
-
gamma-Glutamylcysteine synthetase
-
-
-
-
gamma-Glutamylcysteine synthetase
-
-
GCS
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
tri tri sequential mechanism
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylic acid amide formation
-
-
-
-
carboxamide formation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-glutamate:L-cysteine gamma-ligase (ADP-forming)
Can use L-aminohexanoate in place of glutamate.
CAS REGISTRY NUMBER
COMMENTARY
9023-64-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + alpha-methyl-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-methyl-DL-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + beta-glutamate + L-alpha-aminobutyrate
ADP + phosphate + beta-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + beta-methyl-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + beta-methyl-DL-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + D-Glu + L-2-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
-
-
-
?
ATP + D-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
-
-
ir
ATP + DL-alpha-aminomethylglutarate + L-alpha-aminobutyrate
ADP + phosphate + DL-alpha-aminomethylglutaryl-L-alpha-aminobutyrate
-
-
ir
ATP + DL-alpha-aminomethylsuccinate + L-alpha-aminobutyrate
ADP + phosphate + DL-alpha-aminomethylsuccinyl-L-alpha-aminobutyrate
-
-
ir
ATP + DL-beta-aminoadipate + L-alpha-aminobutyrate
ADP + phosphate + DL-beta-aminoadipyl-L-alpha-aminobutyrate
-
-
ir
ATP + L-Glu + beta-chloro-L-alanine
ADP + phosphate + gamma-L-Glu-beta-chloro-L-alanine
-
-
ir
ATP + L-Glu + DL-allylglycine
ADP + phosphate + gamma-L-Glu-DL-allylglycine
-
-
ir
ATP + L-Glu + DL-beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-DL-beta-amino-iso-butyrate
-
-
ir
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
-
-
ir
ATP + L-Glu + L-alanine
ADP + phosphate + gamma-L-Glu-L-alanine
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
ir
ATP + L-Glu + L-alpha-aminoheptanoate
ADP + phosphate + gamma-L-Glu-L-alpha-aminoheptanoate
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
ir
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
-
-
ir
ATP + L-Glu + L-homoserine
ADP + phosphate + gamma-L-Glu-L-homoserine
-
-
ir
ATP + L-Glu + L-norleucine
ADP + phosphate + gamma-L-Glu-L-norleucine
-
-
ir
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
-
-
ir
ATP + L-Glu + L-serine
ADP + phosphate + gamma-L-Glu-L-serine
-
-
ir
ATP + L-Glu + L-threonine
ADP + phosphate + gamma-L-Glu-L-threonine
-
-
ir
ATP + L-Glu + S-methyl-L-cysteine
ADP + phosphate + gamma-L-Glu-S-methyl-L-cysteine
-
-
ir
ATP + N-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + N-methyl-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + threo-beta-hydroxy-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + threo-beta-hydroxy-DL-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + threo-gamma-hydroxy-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + threo-gamma-hydroxy-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + alpha-methyl-L-glutamate + 2-aminobutyrate
ADP + phosphate + gamma-L-glutamyl-2-aminobutyrate
-
-
-
-
?
ATP + alpha-methylglutamate + L-Cys
ADP + phosphate + alpha-methylglutamyl-L-Cys
-
i.e. 2-amino-2-methylpentanedioate
-
-
?
ATP + beta-aminoglutarate + L-Cys
ADP + phosphate + beta-aminoglutaryl-L-Cys
-
i.e. 3-aminopentanedioate
-
-
?
ATP + beta-Glu + L-Cys
ADP + phosphate + beta-Glu-L-Cys
-
17.6% of the activity relative to L-Glu
-
-
?
ATP + beta-methylglutamate + L-Cys
ADP + phosphate + beta-methylglutamyl-L-Cys
-
i.e. 2-amino-3-methylpentanedioate
-
-
?
ATP + L-Glu + beta-chloro-L-Ala
ADP + phosphate + gamma-L-Glu-L-beta-chloro-L-Ala
-
-
-
-
?
ATP + L-Glu + DL-allylglycine
ADP + phosphate + gamma-L-Glu-DL-allylglycine
-
-
-
-
?
ATP + L-Glu + hydroxylamine
ADP + phosphate + gamma-L-Glu-hydroxylamine
-
slow reaction rate
-
?
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
?
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
-
-
-
-
?
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
-
-
-
-
?
ATP + L-Glu + S-methyl-L-Cys
ADP + phosphate + gamma-L-Glu-S-methyl-L-Cys
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + N-methyl-L-glutarate + L-Cys
ADP + phosphate + N-methyl-L-glutaryl-L-Cys
-
-
-
-
?
ATP + threo-beta-hydroxy-L-Glu + L-Cys
ADP + phosphate + threo-beta-hydroxy-L-Glu-L-Cys
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
assay at pH 8
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
1121, 1122, 1123, 1124, 1125, 1129, 1130, 1132, 1133, 1134, 1135, 1136, 1138, 1139, 1144, 1147, 1150
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate limiting step in GSH de novo biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
part of GSH 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-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step of the chemoprotective glutathione synthesis
-
?
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
-
rate-limiting enzyme in GSH synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
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
-
mechanisms in regulation of GCLC and GCLM expression, 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
?
-
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
?
-
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, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
-
differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation
-
-
?
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
?
-
-
post-translational regulation of GCL, overview
-
-
?
additional information
?
-
-
tumor development in gut tissue does not affect GCS enzyme activity
-
-
?
additional information
?
-
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate limiting step in GSH de novo biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
part of GSH 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-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step of the chemoprotective glutathione synthesis
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
rate-limiting enzyme in GSH synthesis
-
-
?
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
-
mechanisms in regulation of GCLC and GCLM expression, 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, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
-
differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation
-
-
?
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
?
-
-
post-translational regulation of GCL, overview
-
-
?
additional information
?
-
-
tumor development in gut tissue does not affect GCS enzyme activity
-
-
?
additional information
?
-
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
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
Mg2+
required, bound to the kidney enzyme, involved in enzyme phosphorylation, can be substituted by Mn2+ by 25%
Mg2+
required, bound to the kidney enzyme, involved in enzyme phosphorylation, can be substituted by Mn2+ by only 25%
Mn2+
bound to the kidney enzyme, can substitute for Mg2+ by 25%
Mn2+
bound to the kidney enzyme, can substitute for Mg2+ by only 25%
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-Chloro-4-oxo-L-norvaline
irreversible, binding is reduced by L-glutamate, increased by L-alpha-aminobutyrate, and is completely dependent on divalent cations
L-buthionine-R-sulfoximine
mechanism-based, competitive, reversible
S-nitroso-L-cysteine
inactivation, prevented by pretreatment with ATP and L-SR-buthionine sulfoximine in absence of Mg2+
S-nitroso-L-cysteinylglycine
inactivation, prevented by pretreatment with ATP and L-SR-buthionine sulfoximine in absence of Mg2+
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
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-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-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
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+
L-buthionine-S-sulfoximine
mechanism-based, ATP-dependent, nearly irreversible inhibition in presence of Mg2+ and ATP, if ATP and Mg2+ are remove the activity is restored
buthionine sulfoximine
-
inhibition is about 20times more effectively than with prothionine sulfoximine, and at least 100times more effective than methionine sulfoximine
buthionine sulfoximine
-
GCL mediates the phosphorylation of buthionine sulfoximine, which is required for its tight and irreversible binding to the active site of GCL
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
-
feedback inhibition, subunit GCLM increases the Ki for GSH-mediated feedback inhibition of GCL, competitive to glutamate
methionine sulfoximine
-
of the 4 stereoisomers only L-methionine-S-sulfoximine inhibits
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
-
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
additional information
inhibition mechanisms, no inhibition by L-homocysteine sulfonate
-
additional information
inhibition mechanisms, no inhibition by L-homocysteine sulfonate
-
additional information
-
protein-supplemented diet inhibits expression of heavy subunit
-
additional information
-
7,12-dimethylbenz[a]anthracene does not affect GCS enzyme activity in gut tissue
-
additional information
7,12-dimethylbenz[a]anthracene does not affect GCS enzyme activity in gut tissue
-
additional information
-
oxidative stress dramatically affects GCL holoenzyme formation and activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,3-dimethoxy-1,4-naphthoquinone
-
induces expression of heavy and light subunit
activator protein 1
-
i.e. AP-1, is required for basal expression of the enzyme
-
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
ethanol
-
feeding in vivo increases the enzyme expression, treatment of hepatocytes induces the expression of only the heavy enzyme subunit
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
-
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. Low doses activate high doses inhibits the enzyme
nitric oxide
-
induces expression of heavy and light subunit via direct exposure or interleukin-1 induced
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
additional information
-
effect of miscellaneous treatments on enzyme mRNA expression, overview
-
additional information
-
two-thirds partial hepatectomy increases the enzyme expression
-
additional information
-
GCLC expression is 3fold up-regulated 1 h after induction of edematous pancreatitis
-
additional information
-
subunit GCLM increases the Vmax and Kcat of subunit GCLC, and decreases the Km for glutamate and ATP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
cysteine
-
enzyme from embryo homogenate and from visceral yolk sac homogenate
additional information
additional information
kinetics, kinetic mechanism
-
additional information
additional information
kinetics, kinetic mechanism
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
the Ki for GSH is tissue-dependent
-
additional information
additional information
the Ki for GSH is tissue-dependent
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
-
0.13 microg phosphate/mg protein, measured in tumor tissue after treatment with dietary glutamine
additional information
0.13 microg phosphate/mg protein, measured in tumor tissue after treatment with dietary glutamine
additional information
-
0.2 microg phosphate/mg protein, measured in tumor tissue
additional information
0.2 microg phosphate/mg protein, measured in tumor tissue
additional information
-
about 0.35 mmicrog phosphate/mg protein, measured in jejunal mucosa in normal rats and DMBA-treated rats with and without tumors
additional information
about 0.35 mmicrog phosphate/mg protein, measured in jejunal mucosa in normal rats and DMBA-treated rats with and without tumors
additional information
-
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
additional information
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
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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
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
physiological function
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
GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide gamma-glutamylcysteine. The molecular mechanisms that affect these age-related changes and the complexity of GCL regulation are analyzed. Impairment of the transcriptional activity of Nrf2 contributes to GCL dysregulation in aged rats
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). GSH1_RAT
637
0
72619
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30600
1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE
72600
1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE
24000
-
1 * 74000 + 1 * 24000, SDS-PAGE. One enzyme species of MW 100000 Da detected by SDS-PAGE after cross-linking with dimethylsuberimidate
25000
31000
73000
74000
-
1 * 74000 + 1 * 24000, SDS-PAGE. One enzyme species of MW 100000 Da detected by SDS-PAGE after cross-linking with dimethylsuberimidate
75000
31000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE
73000
-
1 * 73000, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
1 * 72600, heavy catalytic subunit, + 1 * 30600, light regulatory subunit, SDS-PAGE
dimer
heterodimer
enzyme GCL is a heterodimeric enzyme consisting of a catalytic subunit (GCLc) and a modulatory subunit (GCLm), which are encoded by two genes
additional information
?
-
unlike kidney enzyme, most of liver enzyme is in a reduced form which does not have disulfide linkage between heavy and light chain
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, about, catalytic subunit, + 1 * 31000, about, regulatory subunit, SDS-PAGE
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
additional information
quarternary structure, the heavy subunit monomer may be essentially nonfunctional under physiological conditions
additional information
quarternary structure, the heavy subunit monomer may be essentially nonfunctional under physiological conditions
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
-
the holoenzyme consists of a heavy catalytic and a light regulatory subunit, i.e. gamma-GCSh and gamma-GCSl
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
-
myristoylation is responsible for regulation of GCL subunit subcellular localization to membranes and mitochondria, overview
phosphoprotein
additional information
-
post-translational modifications of GCLC, e.g. phosphorylation, myristoylation, caspase-mediated cleavage, have modest effects on GCL activity
phosphoprotein
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K38A
-
mutant enzyme Lys38Arg: small changes in the catalytic properties, mutant enzyme K38N and K38E show marked decrease in enzymatic activity and about 2fold increase in Km for Glu
K38N
site-directed mutagenesis, 50% reduced activity and 2 to 3fold increased Km for L-Glu compared to the wild-type
K38Q
site-directed mutagenesis, 50% reduced activity and 2 to 3fold increased Km for L-Glu compared to the wild-type
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
treatment with 50 mM DTT for more than 1 h at 4°C, leads to some loss of activity, which is partially reversible. Further treatment leads to irreversible loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 10 mM imidazole buffer, pH 8.4, 50 mM DTT, irreversible loss of activity after 4 h
-
50% loss of activity after 6-7 days, only 5% of activity remains after 1 month, substrates protect, almost complete reactivation by addition of 2-5 mM
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
from kidney, liver and erythrocytes, recombinant catalytic subunit and holoenzyme from Escherichia coli to homogeneity
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis, heavy and light subunits, overexpression of catalytic subunit and holoenzyme in Escherichia coli BL21(DE3)
expression of both subunits in H4IIE cells via infection with adenovirus as a vector
-
genes GCLC and GCLM, expression analysis of the genes encoding both C and M subunits of GCL
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both the glutamate-cysteine ligase catalytic (GCLC) and modifier (GCLM) subunit mRNA levels are upregulated in response to a lack of cysteine or other essential amino acids, independent of GSH levels. In liver of rats fed sulfur amino acid-deficient diets, induction of ATF4 and phosphorylation of eIF2alpha are associated with higher levels of GCLC and GCLM mRNA
-
fibroblast growth factor 9 treatment alone induces a decrease in hydrogen peroxide level, an increase in glutathione content, and an upregulation of gamma-glutamylcysteine synthetase and heme oxygenase 1 expression in primary cortical neurons but not in astrocytes. Simultaneous treatmentwith fibroblast growth factor 9 and 1-methyl-4-phenylpyridinium prevents 1-methyl-4-phenylpyridinium-induced neuron death and H2O2 overproduction but does not affect the fibroblast growth factor 9-increased gamma-GCS and HO-1 protein expression
-
in interscapular brown adipose tissue, nitric oxide induces in vivo glutathione synthesis through activation of glutamate-cysteine ligase mRNA and protein expression. This effect appears to be mediated by nuclear factor kappaB activation
-
red ginseng extract upregulates catalytic subunit of GCL and heme oxydase-1. Heme oxidase-1 and GCL catalytic subunit induction via Nrf2 activation may contribute to cytoprotection exerted by red ginseng extract against PCB126-induced oxidative stress
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
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
medicine
pharmacology
-
rat model of glutathione depletion using an adenovirus vector with short hairpin RNA against gamma-glutamylcysteine synthetase heavy chain subunit. In the acute 6 or 24 h or subacute 7 days toxicity tests, rats were administered the drugs once or once a day for a week, respectively. Plasma biochemical markers for hepatotoxicity were measured. The 6 and 24 h toxicity test of diclofenac, and the 24 h and 7 days toxicity tests of flutamide show significant serum alanine aminotransferase elevations. The 24 h toxicity test of flutamide shows a slight bilirubin elevation, and histological hepatotoxicity. The 7 days toxicity test of flutamide also demonstrates histological hepatotoxicity
medicine
-
the enzyme may be a key factor in the chemopreventive potential of coffee components kahweol and cafestol
medicine
suitability of treatment of humans with exogenous enzyme gamma-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Huang, C.S.; Moore, W.R.; Meister, A.
On the active site thiol of gamma-glutamylcysteine synthetase: relationship to catalysis, inhibition, and regulation
Proc. Natl. Acad. Sci. USA
85
2464-2468
1988
Escherichia coli, Rattus norvegicus
Moore, W.; Wiener, H.L.; Meister, A.
Inactivation of gamma-glutamylcysteine synthetase, but not of glutamine synthetase, by S-sulfocysteine and S-sulfohomocysteine
J. Biol. Chem.
262
16771-16777
1987
Rattus norvegicus
Seelig, G.F.; Meister.A.
gamma-Glutamylcysteine synthetase from erythrocytes
Methods Enzymol.
113
390-392
1985
Rattus norvegicus
Seelig, G.F.; Meister, A.
Glutathione biosynthesis: gamma-Glutamylcysteine synthetase from rat kidney
Methods Enzymol.
113
379-390
1985
Rattus norvegicus
Seelig, G.F.; Simondsen, R.P.; Meister, A.
Reversible dissociation of gamma-glutamylcysteine synthetase into two subunits
J. Biol. Chem.
259
9345-9347
1984
Rattus norvegicus
Seelig, G.F.; Meister, A.
gamma-Glutamylcysteine synthetase from erythrocytes
Anal. Biochem.
141
510-514
1984
Rattus norvegicus
Seelig, G.F.; Meister, A.
gamma-Glutamylcysteine synthetase. Interaction of an essential sulfhydryl group
J. Biol. Chem.
259
3534-3538
1984
Rattus norvegicus
Griffith, O.W.; Meister, A.
Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine)
J. Biol. Chem.
254
7558-7560
1979
Rattus norvegicus
Griffith, O.W.; Anderson, M.E.; Meister, A.
Inhibition of glutathione biosynthesis by prothionine sulfoximine (S-n-propyl homocysteine sulfoximine), a selective inhibitor of gamma-glutamylcysteine synthetase
J. Biol. Chem.
254
1205-1210
1979
Rattus norvegicus
Sekura, R.; Meister, A.
gamma-Glutamylcysteine synthetase. Further purification, half of the sites" reactivity, subunits, and specificity
J. Biol. Chem.
252
2599-2605
1977
Rattus norvegicus
Orlowski, M.; Meister, A.
gamma-Glutamylcysteine synthetase (rat kidney)
Methods Enzymol.
17B
495-500
1971
Rattus norvegicus
-
Richman, P.G.; Orlowski, M.; Meister, A.
Inhibition of gamma-glutamylcysteine synthetase by L-methionine-S-sulfoximine
J. Biol. Chem.
248
6684-6690
1973
Rattus norvegicus
Davis, J.S.; Balinsky, J.B.; Harington, J.S.; Shepherd, J.B.
Assay, purification, properties and mechanism of action of gamma-glutamylcysteine synthetase from the liver of the rat and Xenopus laevis
Biochem. J.
133
667-678
1973
Rattus norvegicus, Xenopus laevis
Yip, B.; Rudolph, F.B.
The kinetic mechanism of rat kidney gamma-glutamylcysteine synthetase
J. Biol. Chem.
251
3563-3568
1976
Rattus norvegicus
Simondsen, R.P.; Meister, A.
Interaction of the D-isomer of gamma-methylene glutamate with an active site thiol of gamma-glutamylcysteine synthetase
J. Biol. Chem.
261
17134-17137
1986
Rattus norvegicus
Chang, L.
The functional involvement of Lys-38 in the heavy subunit of rat kidney gamma-glutamylcysteine synthetase: chemical modification and mutagenesis studies
J. Protein Chem.
15
321-326
1996
Rattus norvegicus
Chang, L.; Chang, C.
Biochemical regulation of the activity of gamma-glutamylcysteine synthetase from rat liver and kidney by glutathione
Biochem. Mol. Biol. Int.
32
697-703
1994
Rattus norvegicus
Huang, C.S.; Anderson, M.E.; Meister, A.
Amino acid sequence and function of the light subunit of rat kidney gamma-glutamylcysteine synthetase
J. Biol. Chem.
268
20578-20583
1993
Rattus norvegicus
Huang, C.S.; Chang, L.S.; Anderson, M.E.; Meister, A.
Catalytic and regulatory properties of the heavy subunit of rat kidney gamma-glutamylcysteine synthetase
J. Biol. Chem.
268
19675-19680
1993
Rattus norvegicus
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)
Gegg, M.E.; Clark, J.B.; Heales, S.J.R.
Determination of glutamate-cysteine ligase (gamma-glutamylcysteine synthetase) activity by high-performance liquid chromatography and electrochemical detection
Anal. Biochem.
304
26-32
2002
Rattus norvegicus
Huber, W.W.; Scharf, G.; Rossmanith, W.; Prustomersky, S.; Grasl-Kraupp, B.; Peter, B.; Turesky, R.J.; Schulte-Hermann, R.
The coffee components kahweol and cafestol induce g-glutamylcysteine synthetase, the rate limiting enzyme of chemoprotective glutathione synthesis, in several organs of the rat
Arch. Toxicol.
75
685-694
2002
Rattus norvegicus
Huang, Z.A.; Yang, H.; Chen, C.; Zeng, Z.; Lu, S.C.
Inducers of gamma-glutamylcysteine synthetase and their effects on glutathione synthetase expression
Biochim. Biophys. Acta
1493
48-55
2000
Rattus norvegicus
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
Yang, H.; Zeng, Y.; Lee, T.D.; Yang, Y.; Ou, X.; Chen, L.; Haque, M.; Rippe, R.; Lu, S.C.
Role of AP-1 in the coordinate induction of rat glutamate-cysteine ligase and glutathione synthetase by tert-butylhydroquinone
J. Biol. Chem.
277
35232-35239
2002
Rattus norvegicus
Shukla, G.S.; Chiu, J.; Hart, B.A.
Enhanced expression of pulmonary gamma-glutamylcysteine synthetase heavy subunit in rats exposed to cadmium aerosols
Toxicol. Appl. Pharmacol.
163
249-259
2000
Rattus norvegicus
Tsai-Turton, M.; Luderer, U.
Gonadotropin regulation of glutamate cysteine ligase catalytic and modifier subunit expression in rat ovary is subunit and follicle stage specific
Am. J. Physiol.
289
E391-402
2005
Rattus norvegicus (P19468)
Lee, J.I.; Kang, J.; Stipanuk, M.H.
Differential regulation of glutamate-cysteine ligase subunit expression and increased holoenzyme formation in response to cysteine deprivation
Biochem. J.
393
181-190
2006
Rattus norvegicus
Chik, K.; Flourie, F.; Arab, K.; Steghens, J.P.
Kinetic measurement by LC/MS of gamma-glutamylcysteine ligase activity
J. Chromatogr. B
827
32-38
2005
Rattus norvegicus (P19468), Homo sapiens (P48506), Homo sapiens
Hansen, J.M.; Lee, E.; Harris, C.
Spatial activities and induction of glutamate-cysteine ligase (GCL) in the postimplantation rat embryo and visceral yolk sac
Toxicol. Sci.
81
371-378
2004
Rattus norvegicus
Dasgupta, A.; Das, S.; Sarkar, P.K.
Thyroid hormone promotes glutathione synthesis in astrocytes by up regulation of glutamate cysteine ligase through differential stimulation of its catalytic and modulator subunit mRNAs
Free Radic. Biol. Med.
42
617-626
2007
Rattus norvegicus
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
Pereda, J.; Escobar, J.; Sandoval, J.; Rodriguez, J.L.; Sabater, L.; Pallardo, F.V.; Torres, L.; Franco, L.; Vina, J.; Lopez-Rodas, G.; Sastre, J.
Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis
Free Radic. Biol. Med.
44
1599-1609
2008
Rattus norvegicus
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
Kaufmann, Y.; Todorova, V.K.; Luo, S.; Klimberg, V.S.
Glutamine affects glutathione recycling enzymes in a DMBA-induced breast cancer model
Nutr. Cancer
60
518-525
2008
Rattus norvegicus, Rattus norvegicus (P19468)
Petrovic, V.; Buzadzic, B.; Korac, A.; Vasilijevic, A.; Jankovic, A.; Korac, B.
L-Arginine supplementation induces glutathione synthesis in interscapular brown adipose tissue through activation of glutamate-cysteine ligase expression: The role of nitric oxide
Chem. Biol. Interact.
182
204-212
2009
Rattus norvegicus
Chen, C.N.; Brown-Borg, H.M.; Rakoczy, S.G.; Ferrington, D.A.; Thompson, L.V.
Aging impairs the expression of the catalytic subunit of glutamate cysteine ligase in soleus muscle under stress
J. Gerontol. A Biol. Sci. Med. Sci.
65
129-137
2010
Rattus norvegicus
Hosomi, H.; Akai, S.; Minami, K.; Yoshikawa, Y.; Fukami, T.; Nakajima, M.; Yokoi, T.
An in vitro drug-induced hepatotoxicity screening system using CYP3A4-expressing and gamma-glutamylcysteine synthetase knockdown cells
Toxicol. In Vitro
24
1032-1038
2010
Rattus norvegicus (P19468)
Morita, M.; Akai, S.; Hosomi, H.; Tsuneyama, K.; Nakajima, M.; Yokoi, T.
Drug-induced hepatotoxicity test using gamma-glutamylcysteine synthetase knockdown rat
Toxicol. Lett.
189
159-165
2009
Rattus norvegicus
Park, S.H.; Jang, J.H.; Chen, C.Y.; Na, H.K.; Surh, Y.J.
A formulated red ginseng extract rescues PC12 cells from PCB-induced oxidative cell death through Nrf2-mediated upregulation of heme oxygenase-1 and glutamate cysteine ligase
Toxicology
278
131-139
2010
Rattus norvegicus
Huang, J.Y.; Chuang, J.I.
Fibroblast growth factor 9 upregulates heme oxygenase-1 and gamma-glutamylcysteine synthetase expression to protect neurons from 1-methyl-4-phenylpyridinium toxicity
Free Radic. Biol. Med.
49
1099-1108
2010
Rattus norvegicus
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
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