ABAT

{{Short description|Protein-coding gene in the species Homo sapiens}}

4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene.{{cite web | title = Entrez Gene: 4-aminobutyrate aminotransferase | url = https://www.ncbi.nlm.nih.gov/gene/18 }} This gene is located in chromosome 16 at position of 13.2.{{cite journal | vauthors = Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H | title = GABA and GABA receptors in the central nervous system and other organs | journal = International Review of Cytology | volume = 213 | pages = 1–47 | date = 2002 | pmid = 11837891 | doi = 10.1016/s0074-7696(02)13011-7 | publisher = Elsevier | isbn = 9780123646170 }} This gene goes by a number of names, including, GABA transaminase, GABAT, 4-aminobutyrate transaminase, NPD009 etc. This gene is mainly and abundant located in neuronal tissues.{{cite journal | vauthors = Jirholt J, Asling B, Hammond P, Davidson G, Knutsson M, Walentinsson A, Jensen JM, Lehmann A, Agreus L, Lagerström-Fermer M | title = 4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease | journal = PLOS ONE | volume = 6 | issue = 4 | pages = e19095 | date = April 2011 | pmid = 21552517 | pmc = 3084265 | doi = 10.1371/journal.pone.0019095 | bibcode = 2011PLoSO...619095J | doi-access = free }} 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids.{{cite journal | vauthors = Markova M, Peneff C, Hewlins MJ, Schirmer T, John RA | title = Determinants of substrate specificity in omega-aminotransferases | journal = The Journal of Biological Chemistry | volume = 280 | issue = 43 | pages = 36409–16 | date = October 2005 | pmid = 16096275 | doi = 10.1074/jbc.m506977200 | doi-access = free }} ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa.{{cite journal | vauthors = Churchich JE | title = 4-Aminobutyrate aminotransferase. Different susceptibility to inhibitors, microenvironment of the cofactor binding site and distance of the catalytic sites | journal = European Journal of Biochemistry | volume = 126 | issue = 3 | pages = 507–11 | date = September 1982 | pmid = 7140743 | doi=10.1111/j.1432-1033.1982.tb06809.x| doi-access = free }} It is identified that almost tierce of human synapses have GABA. 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. In addition, GAD and GABA-AT are responsible in regulating the concentration of GABA.{{cite journal | vauthors = 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 | title = Pseudomonas fluorescens and In Silico Molecular Modeling | journal = Molecules | volume = 23 | issue = 5 | pages = 1128 | date = May 2018 | pmid = 29747438 | doi = 10.3390/molecules23051128 | pmc = 6099672 | doi-access = free }}

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.{{cite journal | vauthors = Salazar-Sánchez JC, Morales-Villagrán A, López-Pérez SJ, Pardo-Peña K, Villalpando-Vargas F, Medina-Ceja L | title = γ-Aminobutyric acid quantification in small volume biological samples through enzymatically induced electrochemiluminescence | journal = Luminescence | volume = 33 | issue = 4 | pages = 722–730 | date = June 2018 | pmid = 29653023 | doi = 10.1002/bio.3469 }} 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. 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. 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.

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. 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. 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.

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.

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.{{cite journal | vauthors = 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 | title = Hypersomnolence-hyperkinetic movement disorder in a child with compound heterozygous mutation in 4-aminobutyrate aminotransferase (ABAT) gene | journal = Brain & Development | volume = 39 | issue = 2 | pages = 161–165 | date = February 2017 | pmid = 27596361 | doi = 10.1016/j.braindev.2016.08.005 | s2cid = 6403837 }} 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. 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).

Decrease level of GABA concentration results in convulsion.{{cite journal | vauthors = Ramirez AK, Lynes MD, Shamsi F, Xue R, Tseng YH, Kahn CR, Kasif S, Dreyfuss JM | title = Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes | journal = Cell Reports | volume = 21 | issue = 11 | pages = 3040–3048 | date = December 2017 | pmid = 29241534 | pmc = 5841536 | doi = 10.1016/j.celrep.2017.11.065 }}

Medicine

Vigabatrin is a drug that is irreparably suppresses GABA transaminase that causes increased amount of GABA in the brain.{{cite journal | vauthors = Brecht EJ, Barsz K, Gross B, Walton JP | title = Increasing GABA reverses age-related alterations in excitatory receptive fields and intensity coding of auditory midbrain neurons in aged mice | journal = Neurobiology of Aging | volume = 56 | pages = 87–99 | date = August 2017 | pmid = 28532644 | doi = 10.1016/j.neurobiolaging.2017.04.003 | pmc = 6347026 }}

Discovery

In a recent study, it was found out that the increase amount of GABA will stop the consequences of drug addiction.{{cite journal | vauthors = Choi S, Storici P, Schirmer T, Silverman RB | title = Design of a conformationally restricted analogue of the antiepilepsy drug Vigabatrin that directs its mechanism of inactivation of gamma-aminobutyric acid aminotransferase | journal = Journal of the American Chemical Society | volume = 124 | issue = 8 | pages = 1620–4 | date = February 2002 | pmid = 11853435 | doi = 10.1021/ja011968d }} The suppression of ABAT which causing the amount of GABA to increase has a connection to children with those suffer from movement disability. This gene is also link as one genetic cause of GERD.

ABAT has been proved that it is important in mitochondrial nucleoside.

References

External links

{{UCSC gene info|ABAT}}