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Information on EC 2.6.1.19 - 4-aminobutyrate-2-oxoglutarate transaminase and Organism(s) Rattus norvegicus and UniProt Accession P50554

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EC Tree
     2 Transferases
         2.6 Transferring nitrogenous groups
             2.6.1 Transaminases
                2.6.1.19 4-aminobutyrate-2-oxoglutarate transaminase
IUBMB Comments
Requires pyridoxal phosphate. Some preparations also act on beta-alanine, 5-aminopentanoate and (R,S)-3-amino-2-methylpropanoate. cf. EC 2.6.1.120, beta-alanine---2-oxoglutarate transaminase.
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This record set is specific for:
Rattus norvegicus
UNIPROT: P50554
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
gaba-t, gaba transaminase, gaba-transaminase, gaba-at, 4-aminobutyrate aminotransferase, gaba aminotransferase, gamma-aminobutyric acid transaminase, gabat, gamma-aminobutyric acid aminotransferase, gamma-aminobutyrate transaminase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
GABA aminotransferase
-
GABA transaminase
-
gamma-aminobutyric acid transaminase
-
4-aminobutyrate aminotransferase
-
-
-
-
4-aminobutyrate-2-ketoglutarate aminotransferase
-
-
-
-
4-aminobutyrate-2-oxoglutarate aminotransferase
-
-
-
-
4-aminobutyrate-2-oxoglutarate transaminase
-
-
-
-
4-aminobutyric acid 2-ketoglutaric acid aminotransferase
-
-
-
-
4-aminobutyric acid aminotransferase
-
-
-
-
aminobutyrate aminotransferase
-
-
-
-
aminobutyrate transaminase
-
-
-
-
aminotransferase, aminobutyrate
-
-
-
-
beta-alanine aminotransferase
-
-
-
-
beta-alanine transaminase
-
-
-
-
beta-alanine-oxoglutarate aminotransferase
-
-
-
-
beta-alanine-oxoglutarate transaminase
-
-
-
-
GABA aminotransferase
-
-
-
-
GABA transaminase
GABA transferase
-
-
-
-
GABA-2-oxoglutarate aminotransferase
-
-
-
-
GABA-2-oxoglutarate transaminase
-
-
-
-
GABA-alpha-ketoglutarate aminotransferase
-
-
-
-
GABA-alpha-ketoglutarate transaminase
-
-
-
-
GABA-alpha-ketoglutaric acid transaminase
-
-
-
-
GABA-alpha-oxoglutarate aminotransferase
-
-
-
-
GABA-oxoglutarate aminotransferase
-
-
-
-
GABA-oxoglutarate transaminase
-
-
-
-
gamma-aminobutyrate aminotransaminase
-
-
-
-
gamma-aminobutyrate transaminase
-
-
-
-
gamma-aminobutyrate-alpha-ketoglutarate aminotransferase
-
-
-
-
gamma-aminobutyrate-alpha-ketoglutarate transaminase
-
-
-
-
gamma-aminobutyrate:alpha-oxoglutarate aminotransferase
-
-
-
-
gamma-aminobutyric acid aminotransferase
-
-
-
-
gamma-aminobutyric acid pyruvate transaminase
-
-
-
-
gamma-aminobutyric acid transaminase
-
-
-
-
gamma-aminobutyric acid-2-oxoglutarate transaminase
-
-
-
-
gamma-aminobutyric acid-alpha-ketoglutarate transaminase
-
-
-
-
gamma-aminobutyric acid-alpha-ketoglutaric acid aminotransferase
-
-
-
-
gamma-aminobutyric transaminase
-
-
-
-
glutamate-succinic semialdehyde transaminase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate
show the reaction diagram
catalytic mechanism of GABA-AT for degradation of GABA into succinic semialdehyde, overview
4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amino group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
4-aminobutanoate:2-oxoglutarate aminotransferase
Requires pyridoxal phosphate. Some preparations also act on beta-alanine, 5-aminopentanoate and (R,S)-3-amino-2-methylpropanoate. cf. EC 2.6.1.120, beta-alanine---2-oxoglutarate transaminase.
CAS REGISTRY NUMBER
COMMENTARY hide
9037-67-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-aminobutanoate + 2-oxoglutarate
4-oxobutanoate + L-glutamate
show the reaction diagram
-
-
-
?
4-aminobutanoate + 2-oxoglutarate
succinate semialdehyde + L-glutamate
show the reaction diagram
-
-
-
?
4-aminobutanoate + 2-oxoglutarate
4-oxobutanoate + L-glutamate
show the reaction diagram
beta-alanine + 2-oxoglutarate
malonic semialdehyde + L-glutamate
show the reaction diagram
L-3-aminoisobutanoate + 2-oxoglutarate
?
show the reaction diagram
-
-
-
-
?
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
4-aminobutanoate + 2-oxoglutarate
succinate semialdehyde + L-glutamate
show the reaction diagram
-
-
-
?
4-aminobutanoate + 2-oxoglutarate
4-oxobutanoate + L-glutamate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
pyridoxal 5'-phosphate
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid
i.e. CPP-115, high inhibition of GABA-AT. Potential mechanism of inactivation of GABA-AT by CPP-115, overview. CPP-115 has been designed to inactivate GABA-AT via a Michael addition mechanism that would lead to a covalent adduct with the enzyme, similar to that with vigabatrin. But it is discovered from the crystal structure of GABAT inactivated by CPP-115 that the enzyme forms a noncovalent, tightly bound complex with CPP-115 via strong electrostatic interactions between the two carboxylate groups in the resulting metabolite with Arg192 and Arg445 in the active site. Inactivation is initiated by Schiff base formation between CPP-115 and the lysine-bound PLP, followed by gamma-proton removal and tautomerization, resulting in a highly reactive Michael acceptor. Before Lys329 can attack this Michael acceptor, catalytic hydrolysis of the difluoromethylenyl group occurs, leading to the PLP-bound dicarboxylate metabolite, which elicits a conformational change in the enzyme and tightly binds to Arg192 and Arg445 via electrostatic interactions. Molecular dynamic simulations and computer modeling indicate a movement of the difluoromethylenyl group of the Michael acceptor away from Lys329 upon enzyme-catalyzed tautomerization, leaving it too far away from Lys329 for nucleophilic attack. The enzyme catalyzes its hydrolysis instead
(S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid
a highly potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of addiction, design, synthesis method and mechanism, overview. Enzyme-bound structure analysis shows binding between the enzyme and a stable PLP-inhibitor noncovalent complex, rather than covalent modification, tautomeric forms of the structure of inhibitor-inactivated GABA-AT (eight theoretical tautomers of inhibitor-inactivated GABA-AT)
vigabatrin
FDA-approved drug, inactivator of GABA-AT, moderate activity
2,4-diaminobutanoate
-
kinetics
2-oxoglutarate
-
-
4-acryloylphenol
-
potent inhibitor
4-Amino-hex-5-enoic acid
-
substrate analogue, irreversible, in vitro and in vivo
4-hydroxybenzaldehyde
-
potent inhibitor
5-fluorouracil
-
-
Aminooxyacetate
-
kinetics
Branched-chain fatty acids
-
-
-
ethanol
-
in presence of disulfiram, i.e. N,N,N’,N’-tetraethylthiuram disulfide
ethanolamine O-sulfate
-
active-site directed, ir, in vitro and in vivo, kinetics
gabaculine
gastrodigenin
-
30.87% inhibition at 0.01 mM
oleanolic acid
-
20.2% inhibition at 0.1 mg/ml
rosmarinic acid
-
40.2% inhibition at 0.1 mg/ml
Succinic semialdehyde
-
substrate inhibition
trimethylcitryl-beta-D-galactopyranoside
-
56.8% inhibition at 0.01 mM
ursolic acid
-
19.9% inhibition at 0.1 mg/ml
Valproic acid
-
65.4% inhibition at 0.01 mM
vigabatrin
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.5
2-oxoglutarate
-
38°C, pH 8.5
4 - 53
4-aminobutanoate
1.05
beta-Alanine
-
-
2.72
L-3-aminoisobutanoate
-
-
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008 - 0.013
2,4-diaminobutanoate
0.00018
2-oxoglutarate
-
38°C, pH 8.5
0.47
4-acryloylphenol
-
-
0.0044
ethanolamine O-sulfate
-
37°C, pH 8.4
0.0066
Succinic semialdehyde
-
38°C, pH 8.5
additional information
additional information
inihbition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0018
gabaculine
Rattus norvegicus
-
IC50: 0.0018 mM, potent and irreversible inhibitor
0.35
vigabatrin
Rattus norvegicus
-
IC50: 0.35 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10
-
38°C, pH 8.5
170
-
pH 7.3, 37°C, liver enzyme
2.5
-
38°C, pH 8.6
260
-
pH 7.3, 37°C, kidney enzyme
4.9
-
38°C, pH 8.6
600
-
pH 7.3, 37°C, brain enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.5 - 8.6
-
-
additional information
-
pI: 6.8
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4 - 9
-
about half-maximal activity at pH 7.4 and about 90% of maximal activity at pH 9
8 - 9.2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
assay at room temperature
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 55
-
about half-maximal activity at 30°C and 55°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
mostly arteries and partly veins of, strong decrease of activity with age
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
GABA transaminase (GABAT) is the key catabolic enzyme of GABA metabolism
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GABT_RAT
500
0
56456
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
103000
-
PAGE
105000
107000
-
calculated from amino acid composition
50000
-
x * 50000, SDS-PAGE
52700
-
2 * 53300, SDS-PAGE, brain enzyme, 2 * 52700, SDS-PAGE, liver enzyme
53300
-
2 * 53300, SDS-PAGE, brain enzyme, 2 * 52700, SDS-PAGE, liver enzyme
57000
-
2 * 57000, SDS-PAGE with or without DTT or urea
additional information
-
compared to liver enzyme, mature form of brain enzyme has an additional peptide at the N-terminus which may be cleaved by liver mitochondrial extract
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 50000, SDS-PAGE
dimer
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35
-
t1/2: 3 h
50
-
3 h, 80% loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
waggle needling attenuates gamma-aminobutyric acid transaminase expression in the injured brain of rats with post-stroke spasticity
when beta-hydroxybutyrate (10 mM) is added to culture medium, GABA-transaminase mRNA expression is significantly suppressed in time- and dose-dependent manners, GABA-T enzymatic activity in beta-hydroxybutyrate-treated astrocytes is also suppressed, in accordance with its gene expression
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
attenuating GABAT activity and enhancing GABA expression are a promising way to relieve spasticity following stroke. The modulation of GABA and its metabolism by acupuncture, particularly waggle needling, might attenuate GABAT and enhance GABA, alleviating post-stroke spasticity. Waggle needling decreases cerebral infarction and alleviates neurological deficits, overview. No significant difference is found between waggle needling group and baclofen group
medicine
-
chronical administration of vigabatrin with drinking water completely and reversibly eliminates the psychophysical evidence of tinnitus
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tamaki, N.; Fujimoto, S.; Mizota, C.; Kikugawa, M.
Identity of beta-alanine-oxo-glutarate aminotransferase and L-beta-aminoisobutyrate aminotransferase in rat liver
Biochim. Biophys. Acta
925
238-240
1987
Rattus norvegicus
Manually annotated by BRENDA team
Cooper, A.J.L.
Glutamate-gamma-aminobutyrate transaminase
Methods Enzymol.
113
80-82
1985
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Matre, M.; Ciesielski, L.; Cash, C.; Mandel, P.
Comparison of the structural characteristics of the 4-aminobutyrate:2-oxoglutarate transaminases from rat and human brain, and of their affinities for certain inhibitors
Biochim. Biophys. Acta
522
385-399
1978
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Tunnicliff, G.; Ngo, T.T.; Rojo-Ortega, J.M.; Barbeau, A.
The inhibition by substrate analogues of gamma-aminobutyrate aminotransferase from mitochondria of different subcellular fractions of rat brain
Can. J. Biochem.
55
479-484
1977
Rattus norvegicus
Manually annotated by BRENDA team
Matre, M.; Ciesielski, L.; Cash, C.; Mandel, P.
Purification and studies on some properties of the 4-aminobutyrate: 2-oxoglutarate transaminase from rat brain
Eur. J. Biochem.
52
157-169
1975
Rattus norvegicus
Manually annotated by BRENDA team
Kaneko, M.; Fujimoto, S.; Kikugawa, M.; Tamaki, N.
Irreversible inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by gabaculine
FEBS Lett.
276
115-118
1990
Rattus norvegicus
Manually annotated by BRENDA team
Lippert, B.; Metcalf, B.W.; Jung, M.J.; Casara, P.
4-Amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain
Eur. J. Biochem.
74
441-445
1977
Pseudomonas fluorescens, Rattus norvegicus
Manually annotated by BRENDA team
Fowler, L.J.; John, R.A.
Active-site-directed irreversible inhibition of rat brain 4-aminobutyrate aminotransferase by ethanolamine O-sulphate in vitro and in vivo
Biochem. J.
130
569-573
1972
Rattus norvegicus
Manually annotated by BRENDA team
Kaneko, M.; Kontani, Y.; Kikugawa, M.; Tamaki, N.
Inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by 5-fluorouracil and alpha-fluoro-beta-alanine
Biochim. Biophys. Acta
1122
45-49
1992
Rattus norvegicus
Manually annotated by BRENDA team
Wu, Y.; Wang, W.; Richerson, G.B.
GABA transaminase inhibition induces spontaneous and enhances depolarization-evoked GABA efflux via reversal of the GABA transporter
J. Neurosci.
21
2630-2639
2001
Rattus norvegicus
Manually annotated by BRENDA team
Cavalotti, C.; Artico, M.; De Santis, S.
Occurence of GABA transaminase in the thymus gland of juvenile and aged rats
Eur. J. Histochem.
43
293-299
1999
Rattus norvegicus
Manually annotated by BRENDA team
Kontani, Y.; Sakata, S.F.; Matsuda, K.; Ohyama, T.; Sano, K.; Tamaki, N.
The mature size of rat 4-aminobutyrate aminotransferase is different in liver and brain
Eur. J. Biochem.
264
218-222
1999
Rattus norvegicus
Manually annotated by BRENDA team
Kontani, Y.; Kawasaki, S.; Kaneko, M.; Matsuda, K.; Sakata, S.F.; Tamaki, N.
Inhibitory effect of ethanol administration on beta-alanine-2-oxoglutarate aminotransferase (GABA aminotransferase) in disulfiram-pretreated rats
J. Nutr. Sci. Vitaminol.
44
165-176
1998
Rattus norvegicus
Manually annotated by BRENDA team
Kang, T.C.; Park, S.K.; Bahn, J.H.; Chang, J.S.; Cho, S.W.; Choi, S.Y.; Won, M.H.
Comparative studies on the GABA-transaminase immunoreactivity in rat and gerbil brains
Mol. Cells
11
321-325
2001
Meriones unguiculatus, Rattus norvegicus
Manually annotated by BRENDA team
Tao, Y.H.; Xu, H.B.; Yang, X.L.
Inactivation of GABA transaminase by 4-acryloylphenol
Bioorg. Med. Chem. Lett.
16
3719-3722
2006
Rattus norvegicus
Manually annotated by BRENDA team
Choi, J.H.; Lee, D.U.
A new citryl glycoside from Gastrodia elata and its inhibitory activity on GABA transaminase
Chem. Pharm. Bull.
54
1720-1721
2006
Rattus norvegicus
Manually annotated by BRENDA team
Patel, A.B.; de Graaf, R.A.; Martin, D.L.; Battaglioli, G.; Behar, K.L.
Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo
J. Neurochem.
97
385-396
2006
Rattus norvegicus
Manually annotated by BRENDA team
Brozoski, T.J.; Spires, T.J.; Bauer, C.A.
Vigabatrin, a GABA transaminase inhibitor, reversibly eliminates tinnitus in an animal model
J. Assoc. Res. Otolaryngol.
8
105-118
2007
Rattus norvegicus
Manually annotated by BRENDA team
Suzuki, Y.; Takahashi, H.; Fukuda, M.; Hino, H.; Kobayashi, K.; Tanaka, J.; Ishii, E.
Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes
Brain Res.
1268
17-23
2009
Rattus norvegicus (P50554)
Manually annotated by BRENDA team
Yang, J.; Johnson, C.; Shen, J.
Detection of reduced GABA synthesis following inhibition of GABA transaminase using in vivo magnetic resonance signal of [13C]GABA C1
J. Neurosci. Methods
182
236-243
2009
Rattus norvegicus
Manually annotated by BRENDA team
Awad, R.; Muhammad, A.; Durst, T.; Trudeau, V.L.; Arnason, J.T.
Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity
Phytother. Res.
23
1075-1081
2009
Rattus norvegicus
Manually annotated by BRENDA team
Juncosa, J.I.; Takaya, K.; Le, H.V.; Moschitto, M.J.; Weerawarna, P.M.; Mascarenhas, R.; Liu, D.; Dewey, S.L.; Silverman, R.B.
Design and mechanism of (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid, a highly potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of addiction
J. Am. Chem. Soc.
140
2151-2164
2018
Rattus norvegicus (P50554), Sus scrofa (P80147)
Manually annotated by BRENDA team
Wang, J.X.; Mu, J.D.; Ma, L.X.; Sun, T.Y.; Qian, X.; Yu, W.Y.; Tian, Y.; Song, Y.; Gan, Y.Y.; Guo, M.W.; Ren, X.X.; Li, J.L.
Waggle needling wields preferable neuroprotective and anti-spastic effects on post-stroke spasticity rats by attenuating gamma-aminobutyric acid transaminase and enhancing gamma-aminobutyric acid
NeuroReport
31
708-716
2020
Rattus norvegicus (P50554), Rattus norvegicus Sprague-Dawley (P50554)
Manually annotated by BRENDA team