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Information on EC 6.3.1.2 - glutamine synthetase and Organism(s) Rattus norvegicus and UniProt Accession P09606
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6.3.1.2 glutamine synthetaseIUBMB Comments
Glutamine synthetase, which catalyses the incorporation of ammonium into glutamate, is a key enzyme of nitrogen metabolism found in all domains of life. Several types have been described, differing in their oligomeric structures and cofactor requirements.
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Word Map
- 6.3.1.2
- aminotransferase
- gg
- glial
- astrocyte
- nitrate
- bilirubin
- sulfoximine
-
alt
- cerebral
- hepatocytes
- retina
-
fibrillary
- cholesterol
- glutaminase
- albumin
- transaminase
- creatinine
-
adenylylation
- triglyceride
- nodule
-
astroglial
- bile
-
neurotransmitter
-
excitatory
-
c-reactive
-
uric
- no3
-
neurotoxicity
-
glutamatergic
- nitrogenase
-
hyperammonemia
-
excitotoxicity
- cirrhosis
- l-methionine
- anabaena
-
periportal
- pii
- cholestasis
- gamma-gt
-
photorespiratory
-
n2-fixing
-
pericentral
- gamma-glutamyltransferase
-
photorespiration
-
corpuscular
- adenylyltransferase
-
drinker
-
assimilatory
-
remobilization
- drug development
- synthesis
- pharmacology
- diagnostics
- heterocysts
- medicine
- analysis
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
glutamine synthetase, gamma-glutamyl transferase, gs-ii, gsiii, taase, glna1, glna2, gln1;2, gln synthetase, gs(1), 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Chloroplast GS2
-
-
-
-
Clone lambda-GS28
-
-
-
-
Clone lambda-GS31
-
-
-
-
Clone lambda-GS8
-
-
-
-
Cytoplasmic GS3
-
-
-
-
Cytosolic GS1
-
-
-
-
Gln isozyme alpha
-
-
-
-
Gln isozyme beta
-
-
-
-
Gln isozyme gamma
-
-
-
-
Glutamate--ammonia ligase
-
-
-
-
glutamate-ammonia ligase
-
-
-
-
Glutamine synthetase
Glutamylhydroxamic synthetase
-
-
-
-
GS
-
-
-
-
GS(1)
-
-
-
-
GS1
-
-
-
-
GS107
-
-
-
-
GS112
-
-
-
-
GS117
-
-
-
-
GS122
-
-
-
-
GS2
-
-
-
-
GSI
-
-
-
-
GSII
-
-
-
-
GSIII
-
-
-
-
Isozyme delta
-
-
-
-
L-Glutamine synthetase
-
-
-
-
N47/N48
-
-
-
-
S2205/S2287
-
-
-
-
Synthetase, glutamine
-
-
-
-
Glutamine synthetase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine
reaction mechanism
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-glutamate:ammonia ligase (ADP-forming)
Glutamine synthetase, which catalyses the incorporation of ammonium into glutamate, is a key enzyme of nitrogen metabolism found in all domains of life. Several types have been described, differing in their oligomeric structures and cofactor requirements.
CAS REGISTRY NUMBER
COMMENTARY
9023-70-5
-
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
Gln + hydroxylamine + ADP
gamma-Glutamylhydroxamate + NH4+ + ?
-
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
a two-step reaction with phosphorylation of L-glutamate by ATP to give gamma-glutamyl phosphate followed by addition of ammonia and release of phosphate resulting in L-glutamine, phopshate and ADP
-
-
?
ATP + glutamate + NH4+
ADP + phosphate + L-glutamine
-
central enzyme of nitrogen metabolism, key enzyme of glutamate metabolism, reduction of local concentrations of glutamate and ammonia
-
-
?
ATP + L-Glu + NH4+
ADP + phosphate + L-Gln
-
1 mol of enzyme can bind 5 M ATP
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
-
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
brain injuries are usually associated with an increase in the expression of the glutamate-converting enzyme glutamine synthetase
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
enzyme regulation involving L-glutamate uptake, Ca2+, and P2X7 receptors, overview
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
the astrocyte-specific glutamine synthetase plays a key role in glutamate recycling and gamma-aminobutyric acid metabolism, it is involved in nitrosative stress response in the brain, overview
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
the enzyme is involved in development of mesial temporal lobe epilepsy, MTLE
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
upon tissue damage, the enzyme endogenous GS is released from glial cells in the extracellular space, where it converts glutamate into glutamine, which is a nonneurotoxic amino acid
-
-
?
additional information
?
-
structure-activity relationship, overview
-
-
?
additional information
?
-
-
deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, overview
-
-
?
additional information
?
-
-
glutamine synthetase protects the spinal cord against hypoxia-induced and GABA(A) receptor-activated axonal depressions, it may inhibit the depression of CAP amplitudes by blocking GABAA receptors, overview. GS significantly reduces the axonal depression effects of isoguvacine
-
-
?
additional information
?
-
-
rats with pentylenetetrazole-induced repetitive epileptic seizures show increased heat shock responseand reduced enzyme activity, overview
-
-
?
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 + glutamate + NH4+
ADP + phosphate + L-glutamine
-
central enzyme of nitrogen metabolism, key enzyme of glutamate metabolism, reduction of local concentrations of glutamate and ammonia
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
brain injuries are usually associated with an increase in the expression of the glutamate-converting enzyme glutamine synthetase
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
enzyme regulation involving L-glutamate uptake, Ca2+, and P2X7 receptors, overview
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
the astrocyte-specific glutamine synthetase plays a key role in glutamate recycling and gamma-aminobutyric acid metabolism, it is involved in nitrosative stress response in the brain, overview
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
the enzyme is involved in development of mesial temporal lobe epilepsy, MTLE
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
-
upon tissue damage, the enzyme endogenous GS is released from glial cells in the extracellular space, where it converts glutamate into glutamine, which is a nonneurotoxic amino acid
-
-
?
additional information
?
-
-
deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, overview
-
-
?
additional information
?
-
-
glutamine synthetase protects the spinal cord against hypoxia-induced and GABA(A) receptor-activated axonal depressions, it may inhibit the depression of CAP amplitudes by blocking GABAA receptors, overview. GS significantly reduces the axonal depression effects of isoguvacine
-
-
?
additional information
?
-
-
rats with pentylenetetrazole-induced repetitive epileptic seizures show increased heat shock responseand reduced enzyme activity, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
Mg2+
-
optimal ratio of MgCl2 to ATP is 2:1 at 1 mM ATP, inhibition at more than 20 mM excess of MgCl2 over ATP
Mn2+
-
optimal concentration is 2 mM, 25% of the maximal activity relative to Mg2+ activation
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
ATP treatment decreases glutamine synthetase activities and protein expression
methionine sulfoximine
-
irreversible inhibition up to 97% in vivo after longterm treatment over 3 h by Intracranial infusion
Ni2+
-
higher affinity for nickel than for the regular co-factor manganese. Upon binding, nickel interferes with the manganese-catalyzed enzymatic activity of recombinant GLUL protein. GLUL activity in testes of animals exposed to nickel sulfate is reduced
P2X7 receptor
-
stimulation of P2X7 receptors for 2 h inhibits both activity and protein expression of glutamine synthetase, periodate-oxidized 2',3'-dialdehyde ATP abolishes the inhibition
-
L-methionine sulfoximine
-
irreversible at high concentrations, competitive with L-Glu
L-methionine sulfoximine
-
S,R-sulfoximine and S-sulfoximine inhibit, R-sulfoximine is ineffective
additional information
structure-activity relationships and inhibitor design, overview
-
additional information
-
3'-O-(4-benzoylbenzoyl)-ATP suppresses the enzyme expression. Removal of extracellular Ca2+ and inhibition of protein kinase C restores the ATP-decreased enzyme expression but fails to restore the P2X7-decreased L-glutamate uptake
-
additional information
-
inhibitory effects of endothelins on the expression of glutamine synthetase, cultured cortical astrocytes maintained with endothelins show an almost complete loss of glutamine synthetase, this coordinated inhibition of astroglial glutamate uptake and turnover, e.g. by ET-1, dissociates when extracellular glutamate concentrations increase, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
epicatechin
-
0.03 mM completely prevents inactivation of glutamine synthetase by peroxynitrite
resveratrol
-
activity is increased by resveratrol at concentrations of 0.01 and 0.1 mM, 0.25 mM resveratrol does not affect activity
trijodothyronine
-
only when cultures are simultaneously treated with growth hormone and dexamethasone
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
optimum varies from about pH 4.8 to 8.5 depending upon the nature and concentration of the divalent cation present
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
no significant changes in the enzyme activity between morphine-treated and control samples
-
no significant changes in the enzyme activity between morphine-treated and control samples
-
cultured cortical astrocytes maintained with endothelins show an almost complete loss of glutamine synthetase
-
no significant changes in the enzyme activity between morphine-treated and control samples
-
quantitative analysis of enzyme content at different epileptic stages compared to control rats, overview
-
quantitative analysis of enzyme content at different epileptic stages compared to control rats, overview
-
no significant changes in the enzyme activity between morphine-treated and control samples
-
no significant changes in the enzyme activity between morphine-treated and control samples
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). GLNA_RAT
373
0
42268
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
44000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivation upon incubation with NADH and benzyl viologen under aerobic conditions, or under anaerobic conditions, with NADH, benzyl viologen, and hydrogen peroxide
-
37528
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
in brain, no significant changes in the enzyme activity between morphine-treated and control samples
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rowe, W.B.
Glutamine synthetase from muscle
Methods Enzymol.
113
199-212
1985
Ovis aries, Rattus norvegicus, Sus scrofa
Meister, A.
Glutamine synthetase from mammalian tissues
Methods Enzymol.
113
185-199
1985
Gallus gallus, Cricetulus griseus, Ovis aries, Homo sapiens, Mammalia, Rattus norvegicus, Sus scrofa
Muriana, F.J.; Relimpio, A.M.
Benzyl viologen inactivation of rat liver glutamine synthetase
J. Biochem.
113
738-741
1993
Rattus norvegicus
Suarez, I.; Bodega, G.; Fernandez, B.
Glutamine synthetase in brain: effect of ammonia
Neurochem. Int.
41
123-142
2002
Rattus norvegicus
dos Santos, A.Q.; Nardin, P.; Funchal, C.; de Almeida, L.M.; Jacques-Silva, M.C.; Wofchuk, S.T.; Goncalves, C.A.; Gottfried, C.
Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells
Arch. Biochem. Biophys.
453
161-167
2006
Rattus norvegicus
Goerg, B.; Qvartskhava, N.; Voss, P.; Grune, T.; Haeussinger, D.; Schliess, F.
Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration
FEBS Lett.
581
84-90
2007
Ovis aries, Rattus norvegicus
Gebhardt, R.; Baldysiak-Figiel, A.; Kruegel, V.; Ueberham, E.; Gaunitz, F.
Hepatocellular expression of glutamine synthetase: an indicator of morphogen actions as master regulators of zonation in adult liver
Prog. Histochem. Cytochem.
41
201-266
2007
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Eid, T.; Ghosh, A.; Wang, Y.; Beckstroem, H.; Zaveri, H.P.; Lee, T.S.; Lai, J.C.; Malthankar-Phatak, G.H.; de Lanerolle, N.C.
Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats
Brain
131
2061-2070
2008
Homo sapiens, Rattus norvegicus
Bidmon, H.J.; Goerg, B.; Palomero-Gallagher, N.; Schleicher, A.; Haeussinger, D.; Speckmann, E.J.; Zilles, K.
Glutamine synthetase becomes nitrated and its activity is reduced during repetitive seizure activity in the pentylentetrazole model of epilepsy
Epilepsia
49
1733-1748
2008
Rattus norvegicus
Hammer, J.; Alvestad, S.; Osen, K.K.; Skare, ?.; Sonnewald, U.; Ottersen, O.P.
Expression of glutamine synthetase and glutamate dehydrogenase in the latent phase and chronic phase in the kainate model of temporal lobe epilepsy
Glia
56
856-868
2008
Rattus norvegicus
Lo, J.; Huang, W.; Chou, Y.; Tseng, C.; Lee, W.; Sun, S.H.
Activation of P2X7 receptors decreases glutamate uptake and glutamine synthetase activity in RBA-2 astrocytes via distinct mechanisms
J. Neurochem.
105
151-164
2008
Rattus norvegicus
Lehmann, C.; Eisner, F.; Engele, J.
Role of endothelins as mediators of injury-induced alterations of glial glutamate turnover
J. Neurosci. Res.
86
660-667
2008
Rattus norvegicus
Berlicki, L.
Inhibitors of glutamine synthetase and their potential application in medicine
Mini Rev. Med. Chem.
8
869-878
2008
Beta vulgaris, Bradyrhizobium japonicum, Chlorella sp., Columba sp., Escherichia coli, Ovis aries, Hordeum vulgare, Hordeum vulgare (P13564), Oryza sativa, Vigna radiata, Pisum sativum, Sorghum sp., Spinacia oleracea, Triticum aestivum, Zea mays, Senna obtusifolia, Rattus norvegicus (P09606), Salmonella enterica subsp. enterica serovar Typhimurium (P0A1P6), Bacillus subtilis (P12425), Homo sapiens (P15104), Mus musculus (P15105), Synechocystis sp. (P77961), Mycobacterium tuberculosis (P9WN39), Mycobacterium tuberculosis H37Rv (P9WN39)
Matsumoto, M.; Ichikawa, T.; Young, W.; Kodama, N.
Glutamine synthetase protects the spinal cord against hypoxia-induced and GABA(A) receptor-activated axonal depressions
Surg. Neurol.
70
122-8
2008
Rattus norvegicus
Bodzon-Kulakowska, A.; Suder, P.; Drabik, A.; Kotlinska, J.H.; Silberring, J.
Constant activity of glutamine synthetase after morphine administration versus proteomic results
Anal. Bioanal. Chem.
398
2939-2942
2010
Rattus norvegicus
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