ABAT

ABAT
Identifiers
Aliases	ABAT , Abat, 9630038C02Rik, AI255750, ENSMUSG00000051226, Gabaat, Gabat, Gm9851, I54, Laibat, X61497, GABA-AT, NPD009, 4-aminobutyrate aminotransferase
External IDs	OMIM: 137150 MGI: 2443582 HomoloGene: 542 GeneCards: ABAT
EC number	2.6.1.22
Gene location (Human)
Chr.	Chromosome 16 (human)
End	8,784,575 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	8,439,432 bp
RNA expression pattern
	Top expressed in
	Brodmann area 23; ; endothelial cell; ; middle temporal gyrus; ; inferior olivary nucleus; ; entorhinal cortex; ; postcentral gyrus; ; external globus pallidus; ; orbitofrontal cortex; ; superior vestibular nucleus; ; Brodmann area 46;
	Top expressed in
	nucleus accumbens; ; left lobe of liver; ; globus pallidus; ; medial vestibular nucleus; ; dorsal tegmental nucleus; ; lateral hypothalamus; ; arcuate nucleus; ; dorsomedial hypothalamic nucleus; ; suprachiasmatic nucleus; ; paraventricular nucleus of hypothalamus;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity ; 4-aminobutyrate transaminase activity ; protein homodimerization activity ; transaminase activity ; iron-sulfur cluster binding ; metal ion binding ; succinate-semialdehyde dehydrogenase binding ; catalytic activity ; (S)-3-amino-2-methylpropionate transaminase activity ; pyridoxal phosphate binding ; 4-aminobutyrate:2-oxoglutarate transaminase activity ;
Cellular component	4-aminobutyrate transaminase complex ; mitochondrial matrix ; neuron projection ; mitochondrion ;
Biological process	positive regulation of dopamine metabolic process ; positive regulation of aspartate secretion ; response to cocaine ; gamma-aminobutyric acid biosynthetic process ; response to hypoxia ; locomotory behavior ; behavioral response to cocaine ; negative regulation of blood pressure ; positive regulation of inhibitory postsynaptic potential ; response to nicotine ; human ageing ; gamma-aminobutyric acid metabolic process ; negative regulation of platelet aggregation ; cerebellum development ; copulation ; neurotransmitter catabolic process ; response to iron ion ; negative regulation of gamma-aminobutyric acid secretion ; exploration behavior ; positive regulation of heat generation ; negative regulation of dopamine secretion ; response to ethanol ; positive regulation of uterine smooth muscle contraction ; positive regulation of insulin secretion ; positive regulation of prolactin secretion ; gamma-aminobutyric acid catabolic process ;
	Sources:Amigo / QuickGO
Orthologs
	18
	268860
	ENSG00000183044
	ENSMUSG00000057880
	P80404
	P61922
	NM_000663 ; NM_001127448 ; NM_020686
	NM_001170978 ; NM_172961
	NP_000654 ; NP_001120920 ; NP_065737
	NP_001164449 ; NP_766549
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 26, 2024

4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene.^[5] This gene is located in chromosome 16 at position of 13.2.^[6] This gene goes by a number of names, including, GABA transaminase, GABAT, 4-aminobutyrate transaminase, NPD009 etc.^[6] This gene is mainly and abundant located in neuronal tissues.^[7] 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids.^[8] ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa.^[9] It is identified that almost tierce of human synapses have GABA.^[6] GABA is a neurotransmitter that has different roles in different regions of the central and peripheral nervous systems. It can be found also in some tissues that do not have neurons.^[6] In addition, GAD and GABA-AT are responsible in regulating the concentration of GABA.^[10]

Characteristic

GABA's feature is that it does not fluorescent nor electroactive which is why it is hard to determine the reaction of enzymes because no peroxidase and dehydrogenase was identified.^[11] One characteristic of GABA is having low lipophilic which results in the difficulty to cross the blood brain barrier. A lot of researchers have been trying to discover molecules that have a property of high lipophilicity.^[10] The quantification of GABA concentration during cell activity needs to have high spatial and temporal resolution. As before, high performance liquid chromatography (HPLC) was used in quantifying GABA concentration levels. In present time, GABA is now analyze, measured in small volume with a short period of time with the use of electrochemiluminescence.^[11] GABA acts as a tropic factor which then affects some cell activity such as rapid cell reproduction, cell death and differentiation. Intracellular communication is also one of the many functions of GABA outside the nervous system.^[11]

Function

4-Aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44.^[5] GABA acts as a tropic factor which then affects some cell activity such as rapid cell reproduction, cell death and differentiation. Intracellular communication is also one of the many functions of GABA outside the nervous system.^[11] GABA-transaminaze enzyme production was made of ABAT gene command. The main function of ABAT acts as inhibition (neurotransmitter), where it prevents overloading activity of the brain from large amount of signals.^[6]

ABAT activates the beginning of deterioration of GABA. Likewise, suppression of ABAT results in depletion of transient lower esophageal sphincter relaxation (TLESR) and acid reflux activity. Treating of GERD is possible means of suppressing ABAT's physiology.^[7]

ABAT Deficiency

ABAT defect is uncommon disorder. The signs and symptoms of this deficiency were observed from a Dutch family, two of the siblings, and a 6-month pediatric Japanese. These patients have same signs and symptoms that were observed. This include low muscle tone or known as floppy baby syndrome, over responsive reflexes and developmental delay.^[12] The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene.^[5] Abnormal GABA-transaminaze enzyme results in encephalopathy which is observed in pediatric patients and this deficiency have life expectancy of less than 2 years and some survived more than the given life expectancy. Abnormal protein that is being set free from uncontrolled amount of GABA will affect the growth of individual (growth hormone).^[6]

Decrease level of GABA concentration results in convulsion.^[13]

Medicine

Vigabatrin is a drug that is irreparably suppresses GABA transaminase that causes increased amount of GABA in the brain.^[14]

Discovery

In a recent study, it was found out that the increase amount of GABA will stop the consequences of drug addiction.^[15] The suppression of ABAT which causing the amount of GABA to increase has a connection to children with those suffer from movement disability.^[12] This gene is also link as one genetic cause of GERD.^[7]

ABAT has been proved that it is important in mitochondrial nucleoside.^[13]

Related Research Articles

γ-Aminobutyric acid, or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.

<span class="mw-page-title-main">GABA receptor</span> Receptors that respond to gamma-aminobutyric acid

The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABA_A and GABA_B. GABA_A receptors are ligand-gated ion channels ; whereas GABA_B receptors are G protein-coupled receptors, also called metabotropic receptors.

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families. The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.

Branched-chain amino acid aminotransferase (BCAT), also known as branched-chain amino acid transaminase, is an aminotransferase enzyme (EC 2.6.1.42) which acts upon branched-chain amino acids (BCAAs). It is encoded by the BCAT2 gene in humans. The BCAT enzyme catalyzes the conversion of BCAAs and α-ketoglutarate into branched chain α-keto acids and glutamate.

Succinic semialdehyde (SSA) is a GABA metabolite. It is formed from GABA by the action of GABA transaminase (4-aminobutyrate aminotransferase) and further oxidised to become succinic acid, which enters TCA cycle. SSA is oxidized into succinic acid by the enzyme succinic semialdehyde dehydrogenase, which uses NAD⁺ as a cofactor. When the oxidation of succinic semialdehyde to succinic acid is impaired, accumulation of succinic semialdehyde takes place which leads to succinic semialdehyde dehydrogenase deficiency.

Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene.

Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.

Gamma-aminobutyric acid (GABA) B receptor, 2 (GABA_B2) is a G-protein coupled receptor subunit encoded by the GABBR2 gene in humans.

<span class="mw-page-title-main">4-aminobutyrate transaminase</span> Class of enzymes

In enzymology, 4-aminobutyrate transaminase, also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction:

Gamma-aminobutyric acid receptor subunit beta-1 is a protein that in humans is encoded by the GABRB1 gene.

GABA transporter 1 (GAT1) also known as sodium- and chloride-dependent GABA transporter 1 is a protein that in humans is encoded by the SLC6A1 gene and belongs to the solute carrier 6 (SLC6) family of transporters. It mediates gamma-aminobutyric acid's translocation from the extracellular to intracellular spaces within brain tissue and the central nervous system as a whole.

Gamma-aminobutyric acid receptor subunit rho-1 is a protein that in humans is encoded by the GABRR1 gene.

Gamma-aminobutyric acid receptor subunit alpha-6 is a protein that in humans is encoded by the GABRA6 gene.

Succinate-semialdehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH5A1 gene.

Gamma-aminobutyric acid receptor subunit alpha-4 is a protein that in humans is encoded by the GABRA4 gene.

Gamma-aminobutyric acid receptor subunit rho-2 is a protein that in humans is encoded by the GABRR2 gene.

GABA_A receptor-γ3, also known as GABRG3, is a protein which in humans is encoded by the GABRG3 gene.

<span class="mw-page-title-main">Gabaculine</span> Chemical compound

Gabaculine is a naturally occurring neurotoxin first isolated from the bacteria Streptomyces toyacaensis, which acts as a potent and irreversible GABA transaminase inhibitor, and also a GABA reuptake inhibitor. Gabaculine is also known as 3-amino-2,3-dihydrobenzoic acid hydrochloride and 5-amino cyclohexa-1,3 dienyl carboxylic acid. Gabaculine increased GABA levels in the brain and had an effect on convulsivity in mice.

Aminooxyacetic acid, often abbreviated AOA or AOAA, is a compound that inhibits 4-aminobutyrate aminotransferase (GABA-T) activity in vitro and in vivo, leading to less gamma-aminobutyric acid (GABA) being broken down. Subsequently, the level of GABA is increased in tissues. At concentrations high enough to fully inhibit 4-aminobutyrate aminotransferase activity, aminooxyacetic acid is indicated as a useful tool to study regional GABA turnover in rats.

4-aminobutyrate---pyruvate transaminase is an enzyme with systematic name 4-aminobutanoate:pyruvate aminotransferase. This enzyme is a type of GABA transaminase, which degrades the neurotransmitter GABA. The enzyme catalyses the following chemical reaction

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000183044 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000057880 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 3 "Entrez Gene: 4-aminobutyrate aminotransferase".
1 2 3 4 5 6 Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H (2002). "GABA and GABA receptors in the central nervous system and other organs". International Review of Cytology. Elsevier. 213: 1–47. doi:10.1016/s0074-7696(02)13011-7. ISBN 9780123646170. PMID 11837891.
1 2 3 Jirholt J, Asling B, Hammond P, Davidson G, Knutsson M, Walentinsson A, Jensen JM, Lehmann A, Agreus L, Lagerström-Fermer M (April 2011). "4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease". PLOS ONE. 6 (4): e19095. Bibcode:2011PLoSO...619095J. doi: 10.1371/journal.pone.0019095 . PMC 3084265 . PMID 21552517.
↑ Markova M, Peneff C, Hewlins MJ, Schirmer T, John RA (October 2005). "Determinants of substrate specificity in omega-aminotransferases". The Journal of Biological Chemistry. 280 (43): 36409–16. doi: 10.1074/jbc.m506977200 . PMID 16096275.
↑ Churchich JE (September 1982). "4-Aminobutyrate aminotransferase. Different susceptibility to inhibitors, microenvironment of the cofactor binding site and distance of the catalytic sites". European Journal of Biochemistry. 126 (3): 507–11. doi: 10.1111/j.1432-1033.1982.tb06809.x . PMID 7140743.
1 2 Tovar-Gudiño E, Guevara-Salazar JA, Bahena-Herrera JR, Trujillo-Ferrara JG, Martínez-Campos Z, Razo-Hernández RS, Santiago Á, Pastor N, Fernández-Zertuche M (May 2018). "Pseudomonas fluorescens and In Silico Molecular Modeling". Molecules. 23 (5): 1128. doi: 10.3390/molecules23051128 . PMC 6099672 . PMID 29747438.
1 2 3 4 Salazar-Sánchez JC, Morales-Villagrán A, López-Pérez SJ, Pardo-Peña K, Villalpando-Vargas F, Medina-Ceja L (June 2018). "γ-Aminobutyric acid quantification in small volume biological samples through enzymatically induced electrochemiluminescence". Luminescence. 33 (4): 722–730. doi:10.1002/bio.3469. PMID 29653023.
1 2 Nagappa M, Bindu PS, Chiplunkar S, Govindaraj P, Narayanappa G, Krishnan A, Bharath MM, Swaminathan A, Saini J, Arvinda HR, Sinha S, Mathuranath PS, Taly AB (February 2017). "Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene". Brain & Development. 39 (2): 161–165. doi:10.1016/j.braindev.2016.08.005. PMID 27596361. S2CID 6403837.
1 2 Ramirez AK, Lynes MD, Shamsi F, Xue R, Tseng YH, Kahn CR, Kasif S, Dreyfuss JM (December 2017). "Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes". Cell Reports. 21 (11): 3040–3048. doi:10.1016/j.celrep.2017.11.065. PMC 5841536 . PMID 29241534.
↑ Brecht EJ, Barsz K, Gross B, Walton JP (August 2017). "Increasing GABA reverses age-related alterations in excitatory receptive fields and intensity coding of auditory midbrain neurons in aged mice". Neurobiology of Aging. 56: 87–99. doi:10.1016/j.neurobiolaging.2017.04.003. PMC 6347026 . PMID 28532644.
↑ Choi S, Storici P, Schirmer T, Silverman RB (February 2002). "Design of a conformationally restricted analogue of the antiepilepsy drug Vigabatrin that directs its mechanism of inactivation of gamma-aminobutyric acid aminotransferase". Journal of the American Chemical Society. 124 (8): 1620–4. doi:10.1021/ja011968d. PMID 11853435.

External links

Human ABAT genome location and ABAT gene details page in the UCSC Genome Browser .