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Information on EC 6.3.1.2 - glutamine synthetase and Organism(s) Mus musculus and UniProt Accession P15105

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IUBMB 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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This record set is specific for:
Mus musculus
UNIPROT: P15105
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The taxonomic range for the selected organisms is: Mus musculus
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
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Glutamine synthetase
-
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
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-glutamate + NH3 = ADP + phosphate + L-glutamine
show the reaction diagram
reaction mechanism
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 hide
9023-70-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
show the reaction diagram
ATP + glutamate + NH4+
ADP + phosphate + L-glutamine
show the reaction diagram
ATP + L-Glu + NH4+
ADP + phosphate + L-Gln
show the reaction diagram
ATP + L-glutamate + hydroxylamine
ADP + phosphate + L-gamma-glutamylhydroxamate
show the reaction diagram
-
photometric determination of GS activity based on formation of an L-gamma-glutamylhydroxamate ferric chloride complex using hydroxylamine instead of ammonia
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
show the reaction diagram
additional information
?
-
structure-activity relationship, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
show the reaction diagram
-
-
-
?
ATP + glutamate + NH4+
ADP + phosphate + L-glutamine
show the reaction diagram
-
central enzyme of nitrogen metabolism, elimination of glutamate from animal brain
-
-
?
ATP + L-glutamate + NH3
ADP + phosphate + L-glutamine
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Li+
-
50 mM LiCl increases activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S)-2-amino-4-[hydroxy(nitroso)amino]butanoic acid
-
glucagon
-
slightly decreases enzyme activity
H2O2
-
1 mM, 3 h, 63% loss of activity. Inactivation is prevented by the iron chelators 2,2'-dipyridylor 1,10-phenanthroline, but not by their non-chelating analogues
methionine sulfoximine
-
treatment with methionine sulfoximine of transgenic mice that overexpresses the mutant human superoxide dismutase SOD1G93A gene, an animalmodel for the primary inherited form of the human neurodegenerative disease amyotrophic lateral sclerosis. This treatment in vivo reduces glutamine synthetase activity measured in vitro by 85% and reduces brain levels of glutamine by 60% and of glutamate by 30% in both the motor cortex and the anterior striatum, while also affecting levels of GABA and glutathione. Methionine sulfoxime treatment significantly extends the lifespan of these mice by 8%
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta-catenin
-
-
-
dexamethasone
-
rapid and marked increase in activity
Insulin
-
-
-
trijodothyronine
-
only when cultures are simultaneously treated with growth hormone and dexamethasone
additional information
-
the enzyme is not affected by dietary glutamine supplementation or by Mycobacterium bovis bacillus Calmette-Guerin infection, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.3 - 4
(2S)-2-amino-4-[hydroxy(nitroso)amino]butanoic acid
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
mice in which glutamine synthetase is selectively but completely eliminated from striated muscle are healthy and fertile. A 3-fold higher escape of ammonia reveals the absence of glutamine synthetase in muscle. After 20 h of fasting, glutamine synthetase-KO mice are not able to mount the 4fold increase in glutamine production across the hindquarter that is observed in control mice. Instead, muscle ammonia production is 5fold higher than in control mice. The fasting-induced metabolic changes are transient and return to fed levels at 36 h of fasting. Glucose consumption and lactate and ketone-body production are similar in glutamine synthetase-KO and control mice. Challenging glutamine synthetase-KO and control mice with intravenous ammonia in stepwise increments reveals that normal muscles can detoxify 2.5 mol ammonia/g muscle h in a muscle glutamine synthetase-dependent manner, with simultaneous accumulation of urea, whereas glutamine synthetase-KO mice respond with accumulation of glutamine and other amino acids, but not urea
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GLNA_MOUSE
373
0
42120
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
-
ubiquitinylation
-
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
treatment with methionine sulfoximine of transgenic mice that overexpresses the mutant human superoxide dismutase SOD1G93A gene, an animalmodel for the primary inherited form of the human neurodegenerative disease amyotrophic lateral sclerosis. This treatment in vivo reduces glutamine synthetase activity measured in vitro by 85% and reduces brain levels of glutamine by 60% and of glutamate by 30% in both the motor cortex and the anterior striatum, while also affecting levels of GABA and glutathione. Methionine sulfoxime treatment significantly extends the lifespan of these mice by 8%
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shin, D.; Park, C.
N-terminal extension of canine glutamine synthetase created by splicing alters its enzymatic property
J. Biol. Chem.
279
1184-1190
2004
Canis lupus familiaris, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
He, Y.; Hakvoort, T.B.; Vermeulen, J.L.; Lamers, W.H.; Van Roon, M.A.
Glutamine synthetase is essential in early mouse embryogenesis
Dev. Dyn.
236
1865-1875
2007
Mus musculus
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Rogero, M.M.; Tirapegui, J.; Vinolo, M.A.; Borges, M.C.; de Castro, I.A.; Pires, I.S.; Borelli, P.
Dietary glutamine supplementation increases the activity of peritoneal macrophages and hemopoiesis in early-weaned mice inoculated with Mycobacterium bovis bacillus Calmette-Guerin
J. Nutr.
138
1343-1348
2008
Mus musculus
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
Calas, A.G.; Richard, O.; Meme, S.; Beloeil, J.C.; Doan, B.T.; Gefflaut, T.; Meme, W.; Crusio, W.E.; Pichon, J.; Montecot, C.
Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice
Neurotoxicology
29
740-747
2008
Mus musculus
Manually annotated by BRENDA team
Ghoddoussi, F.; Galloway, M.; Jambekar, A.; Bame, M.; Needleman, R.; Brusilow, W.
Methionine sulfoximine, an inhibitor of glutamine synthetase, lowers brain glutamine and glutamate in a mouse model of ALS
J. Neurol. Sci.
290
41-47
2010
Mus musculus
Manually annotated by BRENDA team
He, Y.; Hakvoort, T.B.; Koehler, S.E.; Vermeulen, J.L.; de Waart, D.R.; de Theije, C.; ten Have, G.A.; van Eijk, H.M.; Kunne, C.; Labruyere, W.T.; Houten, S.M.; Sokolovic, M.; Ruijter, J.M.; Deutz, N.E.; Lamers, W.H.
Glutamine synthetase in muscle is required for glutamine production during fasting and extrahepatic ammonia detoxification
J. Biol. Chem.
285
9516-9524
2010
Mus musculus
Manually annotated by BRENDA team
Fernandes, S.P.; Dringen, R.; Lawen, A.; Robinson, S.R.
Inactivation of astrocytic glutamine synthetase by hydrogen peroxide requires iron
Neurosci. Lett.
490
27-30
2011
Ovis aries, Mus musculus
Manually annotated by BRENDA team