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Information on EC 6.3.2.3 - glutathione synthase and Organism(s) Rattus norvegicus and UniProt Accession P46413
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6.3.2.3 glutathione synthaseSpecify your search results
Word Map
- 6.3.2.3
- gamma-glutamylcysteine
- dismutase
-
gamma-glutamyl
- catalase
- s-transferase
- sulfoximine
- cadmium
-
5-oxoprolinuria
-
buthionine
- 5-oxoproline
-
hemolytic
- acidosis
- phytochelatins
- transpeptidase
- gamma-gcs
-
school
-
school-based
-
pyroglutamic
-
glutathione-related
-
atp-grasp
-
bullied
-
l-buthionine-s,r-sulfoximine
- juncea
-
6.3.2.2
-
glutathione-deficient
-
homoglutathione
-
gsh-dependent
- medicine
- biotechnology
- synthesis
- analysis
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
glutathione synthetase, glutathione synthase, gsh synthetase, gshs, gsh-s, gsh synthase, tags2, gshii, gshs1, tags1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Glutathione synthase
-
-
-
-
Glutathione synthetase
Glutathione synthetase (tripeptide)
-
-
-
-
GS
GSH synthetase
-
-
-
-
GSHase
-
-
-
-
GSS
-
-
-
-
Phytochelatin synthetase
-
-
-
-
Synthetase, glutathione
-
-
-
-
Glutathione synthetase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + gamma-L-glutamyl-L-cysteine + glycine = ADP + phosphate + glutathione
substrate binding kinetics and mechanism, negative cooperativity of gamma-L-Glu-L-Cys
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid-amide formation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -
SYSTEMATIC NAME
IUBMB Comments
gamma-L-glutamyl-L-cysteine:glycine ligase (ADP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY
9023-62-5
-
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 + beta-aminoglutaryl-L-2-aminobutyrate + Gly
ADP + phosphate + beta-aminoglutaryl-L-2-aminobutyryl-Gly
ATP + DL-gamma-(beta-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + DL-gamma-(beta-methyl)Glu-L-2-aminobutyryl-Gly
-
44% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + DL-gamma-(gamma-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + DL-gamma-(gamma-methyl)Glu-L-2-aminobutyryl-Gly
-
16% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + gamma-Glu-L-Cys + aminooxyacetate
ADP + phosphate + gamma-Glu-Cys-aminoxyacetate
-
53% of the activity relative to Gly
-
-
?
ATP + gamma-Glu-L-Cys + Gly
ADP + phosphate + glutathione
-
-
-
-
?
ATP + gamma-Glu-L-Cys + N-hydroxyglycine
ADP + phosphate + gamma-Glu-Cys-N-hydroxyglycine
-
33% of the activity relative to Gly
-
-
?
ATP + gamma-Glu-S-methylcysteine + Gly
ADP + phosphate + gamma-Glu-S-methylcysteinyl-Gly
-
24% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + gamma-L-Glu-L-alpha-aminobutyrate + Gly
ADP + phosphate + glutathione
-
-
-
r
ATP + Glu-L-2-aminobutyrate + Gly
ADP + phosphate + gamma-Glu-L-Cys-Gly
-
16% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + L-gamma-(alpha-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + L-gamma-(alpha-methyl)Glu-L-2-aminobutyryl-Gly
-
-
-
-
?
ATP + L-gamma-(N-methyl)Glu-L-2-aminobutyrate + Gly
ADP + phosphate + L-gamma-(N-methyl)Glu-L-2-aminobutyryl-Gly
-
52% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + L-gamma-Glu-Gly + Gly
ADP + phosphate + L-gamma-Glu-Gly-Gly
-
8% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + L-gamma-Glu-L-2-aminopentanoic acid + Gly
ADP + phosphate + gamma-Glu-S-methylcysteinyl-Gly
-
9% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + L-gamma-Glu-L-Ala + Gly
ADP + phosphate + L-gamma-Glu-L-Ala-Gly
-
55% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + L-gamma-Glu-L-Cys + Gly
ADP + phosphate + L-gamma-Glu-L-Cys-Gly
-
102% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + L-gamma-Glu-L-Ser + Gly
ADP + phosphate + L-gamma-Glu-L-Ser-Gly
-
77% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + N-acetyl-L-2-aminobutyrate + Gly
ADP + phosphate + N-acetyl-L-2-aminobutyrate-Gly
-
8% of the activity relative to L-gamma-glutamyl-L-2-aminobutyrate
-
-
?
ATP + N-acetyl-L-Cys + Gly
ADP + phosphate + N-acetyl-L-Cys-Gly
-
20% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
CTP + gamma-Glu-L-Cys + Gly
CDP + phosphate + glutathione
-
4% of the activity relative to ATP
-
-
?
GTP + gamma-Glu-L-Cys + Gly
GDP + phosphate + glutathione
-
3% of the activity relative to ATP
-
-
?
ITP + gamma-Glu-L-Cys + Gly
IDP + phosphate + glutathione
-
6% of the activity relative to ATP
-
-
?
UTP + gamma-Glu-L-Cys + Gly
UDP + phosphate + glutathione
-
24% of the activity relative to ATP
-
-
?
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
-
-
-
?
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
the enzyme catalyzes the last step in glutathione biosynthesis
-
-
?
ATP + beta-aminoglutaryl-L-2-aminobutyrate + Gly
ADP + phosphate + beta-aminoglutaryl-L-2-aminobutyryl-Gly
-
-
-
-
?
ATP + beta-aminoglutaryl-L-2-aminobutyrate + Gly
ADP + phosphate + beta-aminoglutaryl-L-2-aminobutyryl-Gly
-
15% of the activity relative to L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + gamma-Glu-aminobutyrate + Gly
ADP + phosphate + ophthalmic acid
-
L-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + gamma-Glu-aminobutyrate + Gly
ADP + phosphate + ophthalmic acid
-
D-gamma-Glu-L-2-aminobutyrate
-
-
?
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
AF333982
-
-
?
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
-
in presence of dithiothreitol
-
?
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
-
wild-type enzyme shows negative cooperativity in binding of gamma-L-Glu-L-Cys
-
r
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
-
second step in the biosynthesis of glutahione
-
r
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
-
-
-
-
?
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
-
glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview
-
-
?
dATP + gamma-Glu-L-Cys + Gly
dADP + phosphate + glutathione
-
75% of the activity relative to ATP
-
-
?
additional information
?
-
-
the enzyme catalyzes ADP-ATP exchange at 0.62% of the rate of tripeptide synthesis
-
-
?
additional information
?
-
-
dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells
-
-
?
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 + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
the enzyme catalyzes the last step in glutathione biosynthesis
-
-
?
ATP + gamma-L-glutamyl-L-cysteine + glycine
ADP + phosphate + glutathione
-
glutathione is a ubiquitous intracellular peptide with diverse functions that include detoxification, antioxidant defense, maintenance of thiol status, and modulation of cell proliferation, whose biosynthesis is tightly regulated, overview. GSH synthase is regulated in a coordinated manner and its up-regulation can further enhance the capacity of the cell to synthesize GSH, enzyme regulation, detailed overview
-
-
?
additional information
?
-
-
dysregulation of GSH synthesis is increasingly being recognized as contributing to the pathogenesis of many pathological conditions including diabetes mellitus, pulmonary fibrosis, cholestatic liver injury, endotoxemia and drug-resistant tumor cells
-
-
?
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
AF333982
-
-
?
ATP + gamma-L-Glu-L-Cys + Gly
ADP + phosphate + glutathione
-
second step in the biosynthesis of glutahione
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K+
Mg2+
K+
-
strict requirement for monovalent cation, maximal activity with K+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
inhibition of ADP-ATP exchange reaction, no effect on tripeptide synthesis
c-jun
AF333982
negative regulation of enzyme expression by blocking the binding of AP-1 to the promotor
-
NEM
-
inhibition of ADP-ATP exchange reaction, no effect on tripeptide synthesis
tert-butylhydroquinone
AF333982
regulatory role, activator protein 1 AP-1-mediated induction of enzyme expression, 35fold increase in activity in recombinant H4IIE cells, induction of c-jun formation, which is a negative regulatory protein blocking the binding of activator protein 1 to the promotor
additional information
-
enzyme expression in not affected by insulin and hydrocortisone treatment or by ethanol-feeding
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
activator protein 1
AF333982
i.e. AP-1, mediates the induction of enzyme expression by tert-butylhydroquinone, binds to the enzyme promotor, antagonisted by c-jun, a dominant negative which is also produced in enhanced levels after treatment with tert-butylhydroquinone
-
buthionine sulfoximine
-
increase in enzyme expression in hepatocytes by 2.55fold after 18 h
monocrotaline
-
treatment of rats with monocrotaline, a pyrrolizidine alkaloid, increases the activity of GS
Thioacetamide
-
increases the enzyme expression and activity in hepatocyte cell culture and in liver 5fold in vivo
tert-butylhydroquinone
-
increase in enzyme expression in hepatocytes 1.7fold
tert-butylhydroquinone
AF333982
regulatory role, activator protein 1 AP-1-mediated induction of enzyme expression, 35fold increase in activity in recombinant H4IIE cells, induction of c-jun formation, which is a negative regulatory protein blocking the binding of activatot protein 1 to the promotor
additional information
tienilic acid induces the glutathione synthetase and all enzymes of the glutathione biosynthesis pathway, oxidative stress response, and phase II drug metabolism as do oxidative and/or electrophilic stresses, e.g. caused by tienilic acid, regulatory effects, overview
-
additional information
-
enzyme expression in not affected by insulin and hydrocortisone treatment or by ethanol-feeding, a partial hepatectomy lead to increase in enzyme expression 2.7fold after 12 h
-
additional information
-
oxidative stress induces the enzyme, key transcription factors include Nrf2/Nrf1 via the antioxidant response element, ARE, activator protein-1, AP-1, and nuclear factor kappa B, NFkappaB. Basal expression requires AP-1 and NFkappaB
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
assay development, activity under different reaction conditions in rat liver
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expression level in presence or absence of tienilic acid, overview
-
tumorigenic cell line derived from OC22 by reiterated treatment with N-methyl-N-nitro-N-nitrosoguanidine
-
a non-tumorigenic cell line of oval cells established from livers of rats undergoing carcinogenesis by the choline deficient/ethionine-supplemented diet for 12 weeks
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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). GSHB_RAT
474
0
52345
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
-78
-
expression of the enzyme is absent after cryopreservation using increasing concentrations of DMSO at -78°C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DMSO
-
expression of the enzyme is absent after cryopreservation using increasing concentrations of DMSO at -78°C
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning of the 2.2 kb 5'-flanking region, DNA sequence determination and analysis, promotor determination, determination of positive and negative regulation regions, e.g. NF1 repressor for induction of enzyme expression by tert-butylhydroquinone, expression in H4IIE cells, ATCC CRL-1548, via transformation by recombinant adenovirus vector
AF333982
cloning of the enzyme promoter and molecular mechanisms of GS transcriptional regulation. The rat GS promoter contains functional AP-1 sites, some of which act as enhancers. It also contains a functional NF1 site that acts as a repressor, and basal expression requires AP-1 and NFkappaB, overview
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Meister, A.
Glutathione synthetase from rat kidney
Methods Enzymol.
113
393-399
1985
Rattus norvegicus
Oppenheimer, L.; Wellner, V.P.; Griffith, O.W.; Meister.A.
Glutathione synthetase. Purification from rat kidney and mapping of the substrate binding sites
J. Biol. Chem.
254
5184-5190
1979
Rattus norvegicus
Huang, C.S.; He, W.; Meister, A.; Anderson, M.E.
Amino acid sequence of rat kidney glutathione synthetase
Proc. Natl. Acad. Sci. USA
92
1232-1236
1995
Rattus norvegicus
Cornell, J.S.; Meister, A.
Glutathione and gamma-glutamyl cycle enzymes in crypt and villus tip cells of rat jejunal mucosa
Proc. Natl. Acad. Sci. USA
73
420-422
1976
Rattus norvegicus
Luo, J.L.; Huang, C.S.; Babaoglu, K.; Anderson, M.E.
Novel kinetics of mammalian glutathione synthetase: characterization of gamma-glutamyl substrate cooperative binding
Biochem. Biophys. Res. Commun.
275
577-581
2000
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
Homo sapiens, Rattus norvegicus
Volohonsky, G.; Tuby, C.N.; Porat, N.; Wellman-Rousseau, M.; Visvikis, A.; Leroy, P.; Rashi, S.; Steinberg, P.; Stark, A.A.
A spectrophotometric assay of gamma-glutamylcysteine synthetase and glutathione synthetase in crude extracts from tissues and cultured mammalian cells
Chem. Biol. Interact.
140
49-65
2002
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 (AF333982)
Stevenson, D.J.; Morgan, C.; McLellan, L.I.; Helen Grant, M.
Reduced glutathione levels and expression of the enzymes of glutathione synthesis in cryopreserved hepatocyte monolayer cultures
Toxicol. In Vitro
21
527-532
2007
Rattus norvegicus
Lu, S.C.
Regulation of glutathione synthesis
Mol. Aspects Med.
30
42-59
2008
Homo sapiens, Mus musculus, Rattus norvegicus
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