ABAT

Last updated
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000663
NM_001127448
NM_020686

NM_001170978
NM_172961

RefSeq (protein)

NP_000654
NP_001120920
NP_065737

NP_001164449
NP_766549

Location (UCSC) Chr 16: 8.67 – 8.78 Mb Chr 16: 8.33 – 8.44 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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 Main inhibitory neurotransmitter in the mammalian brain

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: GABAA and GABAB. GABAA receptors are ligand-gated ion channels ; whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptors.

<span class="mw-page-title-main">Succinic semialdehyde dehydrogenase deficiency</span> Rare disorder involving deficiency in GABA degradation

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.

<span class="mw-page-title-main">Branched-chain amino acid aminotransferase</span> Aminotransferase enzyme

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.

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

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.

<span class="mw-page-title-main">Gamma-aminobutyric acid receptor subunit gamma-2</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">Gamma-aminobutyric acid receptor subunit alpha-1</span> Protein-coding gene in humans

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

<span class="mw-page-title-main">GABBR2</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid (GABA) B receptor, 2 (GABAB2) 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:

<span class="mw-page-title-main">GABRB1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">GABA transporter type 1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">GABRR1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">GABRA6</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">Aldehyde dehydrogenase 5 family, member A1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">GABRA4</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">GABRR2</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">GABRG3</span> Protein-coding gene in the species Homo sapiens

GABAA 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.

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

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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000183044 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000057880 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 "Entrez Gene: 4-aminobutyrate aminotransferase".
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.