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Information on EC 6.3.2.2 - glutamate-cysteine ligase
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EC Tree
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
- heme
- peroxidase
-
plexiform
-
buthionine
- sulfoximine
- nerve
- superoxide
- s-transferase
- fiber
- dismutase
- oxygenase-1
-
tomography
-
coherence
-
amacrine
-
neuroprotective
-
2-related
-
erythroid
- gssg
-
macular
-
cytoprotective
-
nadph:quinone
- glaucoma
- transpeptidase
-
dentate
-
intravitreal
-
nf-e2-related
-
nrf2-dependent
-
l-buthionine-s,r-sulfoximine
-
nrf2-mediated
-
fovea
-
gsh-dependent
-
glutathione-related
- gamma-glutamyltranspeptidase
- phytochelatins
-
factor-erythroid
- tert-butylhydroquinone
-
ech-associated
-
nrf2-regulated
-
nrf2-are
-
oxidoreductase-1
-
gsh-related
-
spectral-domain
-
kelch-like
-
subgranular
-
peripapillary
-
sd-oct
- medicine
-
spectralis
- synthesis
- pharmacology
- drug development
-
gsh-depleting
- agriculture
- biotechnology
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
Ace-GCL, Asuc_1947, AtGCL, bifunctional glutathione synthetase, bifunctional GSH synthetase, bifunctional L-glutathione synthetase, gamma -GCS, gamma-ECL, Gamma-ECS, gamma-GC, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Asuc_1947
bifunctional glutathione synthetase
bifunctional GSH synthetase
bifunctional L-glutathione synthetase
Gamma-ECS
gamma-GCS
gamma-GCS-GS
-
bifunctional enzyme accounts for gamma-glutamylcysteine synthetase and glutathione synthetase activities
gamma-glutamate-cysteine ligase-glutathione synthetase
-
bifunctional enzyme
gamma-glutamate-cysteine ligase/glutathione synthetase
-
bifunctional enzyme
gamma-glutamyl-cysteine ligase
gamma-Glutamyl-L-cysteine synthetase
-
-
-
-
gamma-glutamylcysteine ligase
gamma-Glutamylcysteine synthetase
gamma-glutamylcysteine synthetase-glutathione synthetase
-
bifunctional enzyme
gamma-Glutamylcysteinyl-synthetase
-
-
-
-
GCL
GCLC
GCLM
GCS
GCSGS
GLCL
glutamate cysteine ligase
glutamate-cysteine ligase
glutathione biosynthesis bifunctional protein GshAB
GSH1
GshA
gshAB
GshF
GSHI
PhGshA II
PSHAa0937
Synthetase, gamma-glutamylcysteine
-
-
-
-
additional information
Gamma-ECS
-
-
-
-
gamma-glutamylcysteine ligase
bifunctional enzyme, also glutathione synthetase activity, EC 6.3.2.3
gamma-Glutamylcysteine synthetase
-
-
-
-
gamma-Glutamylcysteine synthetase
-
-
gamma-Glutamylcysteine synthetase
-
-
gamma-Glutamylcysteine synthetase
Streptococcus agalactiae serogroup V ATCC BAA-611 / 2603 V/R
-
-
GCL
-
-
GCS
-
-
-
-
glutathione biosynthesis bifunctional protein GshAB
UniProt
glutathione biosynthesis bifunctional protein GshAB
UniProt
GshF
-
bifunctional enzyme gamma-glutamate-cysteine ligase-glutathione synthetase; bifunctional gamma-glutamate-cysteine ligase/glutathione synthetase
additional information
Streptococcus agalactiae serogroup V ATCC BAA-611 / 2603 V/R
cf. EC 6.3.2.3
-
additional information
-
enzyme belongs to the superfamily of carboxylate-amine/ammonia ligases, together with glutathione synthase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
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
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
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
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
no conserved cysteine residue in the active site
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
no conserved cysteine residue in the active site
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
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
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
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
Cys553 is not the active site residue
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
rapid equilibrium random ter-reactant mechanism, substrate binding modeling, active site model
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
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
reaction mechanism via phosphorylated glutamate intermediate
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
reaction mechanism
-
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
reaction mechanism, overview
P74515
ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine
reaction mechanism
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
Ligation
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
L-glutamate:L-cysteine gamma-ligase (ADP-forming)
Can use L-aminohexanoate in place of glutamate.
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CAS REGISTRY NUMBER
COMMENTARY
9023-64-7
-
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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-ethyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-ethyl-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + alpha-methyl-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-methyl-DL-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + alpha-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + alpha-methyl-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
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-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 + beta-methylglutamate + L-Cys
ADP + phosphate + beta-methylglutamyl-L-Cys
-
i.e. 2-amino-3-methylpentanedioate
-
-
-
ATP + DL-alpha-aminoadipate + L-cysteine
ADP + phosphate + DL-aminoadipyl-L-cysteine
-
about 10% of the activity with L-glutamate
-
-
?
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 + glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
random ter-reactant mechanism with a preferred binding order
-
-
?
ATP + L-Glu + (R)-beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-(R)-beta-amino-iso-butyrate
-
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
-
2fold as reactive as the R-isomer
-
ir
ATP + L-Glu + allo-L-threonine
ADP + phosphate + gamma-L-Glu-allo-L-threonine
-
-
ir
ATP + L-Glu + beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-beta-amino-iso-butyrate
-
-
ir
ATP + L-Glu + beta-cyano-L-alanine
ADP + phosphate + gamma-L-Glu-beta-cyano-L-alanine
-
-
ir
ATP + L-Glu + DL-beta-amino-iso-butyrate
ADP + phosphate + gamma-L-Glu-DL-beta-amino-iso-butyrate
-
-
ir
ATP + L-Glu + gamma-aminobutyrate
ADP + phosphate + gamma-L-Glu-gamma-aminobutyrate
-
mutant R366A
-
r
ATP + L-Glu + gamma-aminobutyrate
ADP + phosphate + L-Glu-gamma-aminobutyrate
-
-
-
ir
ATP + L-Glu + hydroxylamine
ADP + phosphate + gamma-L-Glu-hydroxylamine
-
slow reaction rate
-
-
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + gamma-L-Glu-2-aminobutyrate
-
-
-
?
ATP + L-Glu + L-alpha-aminoheptanoate
ADP + phosphate + gamma-L-Glu-L-alpha-aminoheptanoate
-
-
ir
ATP + L-Glu + L-C-allylglycine
ADP + phosphate + gamma-L-Glu-L-C-allylglycine
-
-
ir
ATP + L-Glu + L-isoleucine
ADP + phosphate + gamma-L-Glu-L-isoleucine
-
-
ir
ATP + L-Glu + L-leucine
ADP + phosphate + gamma-L-Glu-L-leucine
-
-
ir
ATP + L-Glu + L-valine
ADP + phosphate + gamma-L-Glu-L-valine
-
-
ir
ATP + L-Glu + n-propylamine
ADP + phosphate + N-propyl-L-glutamine
-
-
-
-
?
ATP + L-Glu + O-methyl-DL-serine
ADP + phosphate + gamma-L-Glu-O-methyl-DL-serine
-
-
ir
ATP + L-Glu + S-methyl-L-Cys
ADP + phosphate + gamma-L-Glu-L-S-methyl-Cys
-
-
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
ATP + N-methyl-L-glutarate + L-Cys
ADP + phosphate + N-methyl-L-glutaryl-L-Cys
-
-
-
-
-
ATP + threo-beta-hydroxy-DL-glutamate + L-alpha-aminobutyrate
ADP + phosphate + threo-beta-hydroxy-DL-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + threo-beta-hydroxy-L-Glu + L-Cys
ADP + phosphate + threo-beta-hydroxy-L-Glu-L-Cys
-
-
-
-
-
ATP + threo-gamma-hydroxy-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + threo-gamma-hydroxy-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
glutamate + ATP + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
assay at pH 8.2
-
-
?
GTP + L-Glu + L-Cys
GDP + phosphate + gamma-L-Glu-L-Cys
-
87% of the activity relative to ATP
-
-
-
L-glutamate + L-cysteine + ATP
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
UTP + L-Glu + L-Cys
UDP + phosphate + gamma-L-Glu-L-Cys
-
12% of the activity relative to ATP
-
-
-
ATP + D-Glu + L-2-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
-
-
-
?
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 + D-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-D-Glu-L-alpha-aminobutyrate
-
-
ir
ATP + D-Glu + L-Cys
ADP + phosphate + D-Glu-L-Cys
-
8.5% of the activity relative to L-Glu
-
-
-
ATP + L-Glu + beta-chloro-L-Ala
ADP + phosphate + gamma-L-Glu-L-beta-chloro-L-Ala
-
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
-
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-Ala
ADP + phosphate + gamma-L-Glu-L-beta-chloro-L-Ala
-
-
-
-
-
ATP + L-Glu + beta-chloro-L-alanine
ADP + phosphate + gamma-L-Glu-beta-chloro-L-alanine
-
-
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
-
-
-
-
-
ATP + L-Glu + DL-allylglycine
ADP + phosphate + gamma-L-Glu-DL-allylglycine
-
-
ir
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
-
-
ir
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
-
14.5% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + Gly
ADP + phosphate + gamma-L-Glu-Gly
-
-
ir
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
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
Escherichia coli B / ATCC 11303
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
60% of the activity relative to L-Cys
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutanoate
ADP + phosphate + gamma-L-Glu-2-aminobutanoate
-
-
-
-
-
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
-
-
-
?
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
-
-
-
?
ATP + L-Glu + L-2-aminobutyrate
ADP + phosphate + L-Glu-2-aminobutyrate
-
-
-
?
ATP + L-Glu + L-Ala
ADP + phosphate + gamma-L-Glu-L-Ala
-
10.9% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-alanine
ADP + phosphate + gamma-L-Glu-L-alanine
-
-
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-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
-
?
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
-
?
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
-
ir
ATP + L-Glu + L-alpha-aminobutyrate
ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
-
-
r
ATP + L-Glu + L-Cys
?
-
enzyme catalyzes the first committed step in the biosynthesis of trypanothione, i.e. diglutathionylspermidine
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
Q56277
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
-
ir
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 and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
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 and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
the enzyme has key influence on glutathione homeostasis
-
?
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
-
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
catalyzes the biosynthesis of the GSH precursor
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate-limiting step in the biosynthesis of glutathione
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
first and rate-limiting step in the GSH biosynthesis
-
ir
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
Escherichia coli B / ATCC 11303
-
catalyzes the biosynthesis of the GSH precursor
-
?
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 the GSH biosynthesis
-
ir
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
-
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
-
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
-
rate-limiting step in glutathione biosynthesis
-
?
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
-
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
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate-limiting step in glutathione biosynthesis
-
ir
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 enzyme in the GSH biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis, regulation mechanism and model
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
regulation and signaling in GSH de novo synthesis pathway
-
?
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
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
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
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
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
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
-
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
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
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
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
-
-
ir
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-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
-
-
ir
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
-
-
ir
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 and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
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 step in the biosynthesis of trypanothione via GSH
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first step in the de novo biosynthesis of the tripeptide glutathione
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate limiting and first step in glutathione biosynthesis
-
ir
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 and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
-
13.7% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-homocysteine
ADP + phosphate + gamma-L-Glu-L-homocysteine
-
-
-
-
-
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
-
17% of the activity relative to L-Cys
-
-
-
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-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-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
-
-
ir
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
-
14% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
-
-
-
-
-
ATP + L-Glu + L-norvaline
ADP + phosphate + gamma-L-Glu-L-norvaline
-
-
ir
ATP + L-Glu + L-Ser
ADP + phosphate + gamma-L-Glu-L-Ser
-
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
-
14.5% of the activity relative to L-Cys
-
-
-
ATP + L-Glu + L-serine
ADP + phosphate + gamma-L-Glu-L-serine
-
-
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
-
allo-L-threonine is a 5fold better substrate than L-threonine
-
ir
ATP + L-Glu + L-threonine
ADP + phosphate + gamma-L-Glu-L-threonine
-
-
ir
ATP + L-Glu + L-threonine
ADP + phosphate + gamma-L-Glu-L-threonine
-
-
ir
ATP + L-Glu + S-methyl-L-Cys
ADP + phosphate + gamma-L-Glu-S-methyl-L-Cys
-
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-S-methyl-L-Cys
-
-
-
-
-
ATP + L-glutamate + 2-aminobutyrate
ADP + phosphate + gamma-L-glutamyl-(2-aminobutyrate)
2-aminobutyrate can replace cysteine, although with a lower activity
-
-
?
ATP + L-glutamate + 2-aminobutyrate
ADP + phosphate + gamma-L-glutamyl-(2-aminobutyrate)
2-aminobutyrate can replace cysteine, although with a lower activity
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Actinobacillus pleuropneumoniae ATCC 55618
-
-
-
-
?
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
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
redox regulation of the enzyme, overview
-
-
?
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 glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
C1KBE8; C1KBE7
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
the enzyme plays a role in disease resistance in Arabidopsis
-
-
?
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 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
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
-
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
-
-
-
-
?
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 glutathione biosynthesis, plays a central role in glutathione homeostasis
-
-
?
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 step in glutathione biosynthesis
-
-
?
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
-
-
-
?
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 glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
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
-
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
-
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
-
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
-
GCL is the key glutathione-synthesizing enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
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
-
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
-
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
-
-
-
-
?
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
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
-
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
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
first step of 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
-
-
-
?
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
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
-
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
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
assay at pH 8
-
-
?
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
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
reaction is catalyzed by the bifunctional enzyme gamma-glutamylcysteine synthetase-glutathione synthetase
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Streptococcus agalactiae serogroup V ATCC BAA-611 / 2603 V/R
-
-
-
?
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
-
-
-
-
?
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
P74515
-
-
-
?
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 the biosynthesis of glutathione, pathway overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
redox regulation of the enzyme, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
chilling stress strongly induces gamm-ECS mRNA
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + N-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + N-methyl-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
ATP + N-methyl-L-glutamate + L-alpha-aminobutyrate
ADP + phosphate + N-methyl-L-glutamyl-L-alpha-aminobutyrate
-
-
ir
additional information
?
-
-
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, CC2 plays no role in GCL redox regulation, overview
-
-
-
additional information
?
-
-
substrate specificity, beta-alanine, (R,S)-beta-amino-n-butyrate, and (R,S)-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
?
-
-
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
?
-
-
enhancement of the glutathione biosynthetic capability, particularly in neuronal tissues, can extend the life span of flies
-
-
-
additional information
?
-
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
?
-
-
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
?
-
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
?
-
hyperthermal stress triggers adaptive increases in intracellular GSH biosynthesis in cnidarians as a protective response to oxidative/nitrosative stress, overview
-
-
-
additional information
?
-
-
hyperthermal stress triggers adaptive increases in intracellular GSH biosynthesis in cnidarians as a protective response to oxidative/nitrosative stress, overview
-
-
-
additional information
?
-
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
?
-
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
?
-
-
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
?
-
-
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
?
-
-
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. 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
?
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
Q97SC0
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
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
-
-
-
additional information
?
-
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, CC2 plays a role in GCL redox regulation, overview
-
-
-
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
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
-
-
-
additional information
?
-
-
Met4 regulates the GSH1 expression in response to GSH availability, model for genetic regulation and control of GSH biosynthesis
-
?
additional information
?
-
-
the bifunctional enzyme GshF exhibits the activities of glutamate-cyseteine ligase, EC 6.3.2.2, and glutathione synthetase, EC 6.3.2.3
-
-
-
additional information
?
-
the bifunctiona enzyme also catalyzes the reaction of EC 6.3.2.3, gltathione synthetase
-
-
-
additional information
?
-
the bifunctiona enzyme also catalyzes the reaction of EC 6.3.2.3, gltathione synthetase
-
-
-
additional information
?
-
-
the bifunctional enzyme GshF exhibits the activities of glutamate-cyseteine ligase, EC 6.3.2.2, and glutathione synthetase, EC 6.3.2.3
-
-
-
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
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
?
-
most of the GSH produced in this pathway is converted to trypanothione
-
?
additional information
?
-
-
the enzyme contains two intramolecular disulfide bridges, CC1 and CC2, CC2 plays no role in GCL redox regulation, overview
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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-Glu + L-Cys
?
-
enzyme catalyzes the first committed step in the biosynthesis of trypanothione, i.e. diglutathionylspermidine
-
-
-
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
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
-
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 and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
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
-
the enzyme has key influence on glutathione homeostasis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
catalyzes the biosynthesis of the GSH precursor
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate-limiting step in the biosynthesis of glutathione
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
P0A6W9
first and rate-limiting step in the GSH biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
Escherichia coli B / ATCC 11303
-
catalyzes the biosynthesis of the GSH precursor
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
P0A6W9
first and rate-limiting step in the GSH biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis
-
?
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
-
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
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first and rate-limiting step in glutathione biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
rate-limiting enzyme in the GSH biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate-limiting step in glutathione biosynthesis, regulation mechanism and model
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
regulation and signaling in GSH de novo synthesis pathway
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
first and rate-limiting step in glutathione biosynthesis
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
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
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
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
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
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
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
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
-
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-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
-
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
rate-limiting step in glutathione biosynthesis, regulation mechanism
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first step in the biosynthesis of trypanothione via GSH
-
?
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
first step in the de novo biosynthesis of the tripeptide glutathione
-
r
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
-
rate limiting and first step in glutathione biosynthesis
-
ir
ATP + L-Glu + L-Cys
ADP + phosphate + gamma-L-Glu-L-Cys
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
-
rate limiting and first step in glutathione biosynthesis, GSH metabolism, overview
-
ir
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
D4N892
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Actinobacillus pleuropneumoniae ATCC 55618
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
A6VQP8
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
A6VQP8
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
redox regulation of the enzyme, 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
C1KBE8 AND C1KBE7
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
the enzyme plays a role in disease resistance in Arabidopsis
-
-
?
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 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
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
-
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
-
-
-
-
?
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 glutathione biosynthesis, plays a central role in glutathione homeostasis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
B2ZG39
rate-limiting step in glutathione biosynthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
P48506 AND P48507
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
P48506 AND P48507
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
P48506
rate-limiting enzyme in glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
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
-
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
-
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
-
GCL is the key glutathione-synthesizing enzyme
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
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
-
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
-
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
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
P97494 AND O09172
-
-
-
?
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
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
-
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
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
-
first step of glutathione synthesis
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Q3IEB7
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Q3IEB7
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
P19468
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
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
-
rate-limiting enzyme in glutathione synthesis
-
-
?
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
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
A0A0U2SCI4
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
A0A0U2SCI4
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
reaction is catalyzed by the bifunctional enzyme gamma-glutamylcysteine synthetase-glutathione synthetase
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Q8DXM9
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Streptococcus agalactiae serogroup V ATCC BAA-611 / 2603 V/R
Q8DXM9
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
D4N891
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
D4N891
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
P74515
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
B4YE15
first step in the biosynthesis of glutathione, pathway overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
-
redox regulation of the enzyme, overview
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + gamma-L-glutamyl-L-cysteine
Q8W4W3
chilling stress strongly induces gamm-ECS mRNA
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
ATP + L-glutamate + L-cysteine
ADP + phosphate + L-glutamyl-L-cysteine
-
-
-
-
?
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
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
?
-
-
hyperthermal stress triggers adaptive increases in intracellular GSH biosynthesis in cnidarians as a protective response to oxidative/nitrosative stress, overview
-
-
-
additional information
?
-
P48506
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
?
-
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
?
-
-
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
?
-
-
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
?
-
-
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. 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
?
-
P97494
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
Q97SC0
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
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
-
-
-
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
P19468
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH, regulation by dephosphorylation/phosphorylation
-
?
additional information
?
-
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
?
-
-
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
?
-
P19468
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
?
-
-
Met4 regulates the GSH1 expression in response to GSH availability, model for genetic regulation and control of GSH biosynthesis
-
?
additional information
?
-
-
the bifunctional enzyme GshF exhibits the activities of glutamate-cyseteine ligase, EC 6.3.2.2, and glutathione synthetase, EC 6.3.2.3
-
-
-
additional information
?
-
-
the bifunctional enzyme GshF exhibits the activities of glutamate-cyseteine ligase, EC 6.3.2.2, and glutathione synthetase, EC 6.3.2.3
-
-
-
additional information
?
-
-
GSH synthesis is controlled by the amount of enzyme, L-cysteine and by feedback inhibition exerted by GSH
-
?
additional information
?
-
Q26820
most of the GSH produced in this pathway is converted to trypanothione
-
?
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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
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
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
-
; binding of L-Glu to the enzyme increases the binding affinity for ATP by 18fold
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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+
Mg2+
Mn2+
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
Cu2+
-
2 divalent metal ions per enzyme molecule are bound, can be replaced by Mn2+ and Mg2+, binding mechanism and kinetics, overview
Mg2+
-
divalent metal ion required, especially Mg2+, optimal concentration depending on ATP concentration
Mg2+
-
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+
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+
-
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+
Mn2+
-
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
Mn2+
bound to the kidney enzyme, can substitute for Mg2+ by 25%; bound to the kidney enzyme, can substitute for Mg2+ by only 25%
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INHIBITOR
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
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
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
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
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
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,