This enzyme is found in prokaryotes, plants, fungi, and animals (including humans).[1] Pigs have often been used when studying how this protein may work in humans.[2]
Enzyme Commission number
GABA-T is Enzyme Commission number 2.6.1.19. This means that it is in the transferase class of enzymes, the nitrogenous transferase sub-class and the transaminase sub-subclass.[3] As a nitrogenous transferase, its role is to transfer nitrogenous groups from one molecule to another. As a transaminase, GABA-T's role is to move functional groups from an amino acid and a α-keto acid, and vice versa. In the case of GABA-T, it takes a nitrogen group from GABA and uses it to create L-glutamate.
Reaction pathway
In animals, fungi, and bacteria, GABA-T helps facilitate a reaction that moves an amine group from GABA to 2-oxoglutarate, and a ketone group from 2-oxoglutarate to GABA.[4][5][6] This produces succinate semialdehyde and L-glutamate.[4] In plants, pyruvate and glyoxylate can be used in the place of 2-oxoglutarate.[7] catalyzed by the enzyme 4-aminobutyrate—pyruvate transaminase:
The primary role of GABA-T is to break down GABA as part of the GABA-Shunt.[2] In the next step of the shunt, the semialdehyde produced by GABA-T will be oxidized to succinic acid by succinate-semialdehyde dehydrogenase, resulting in succinate. This succinate will then enter mitochondrion and become part of the citric acid cycle.[8] The critic acid cycle can then produce 2-oxoglutarate, which can be used to make glutamate, which can in turn be made into GABA, continuing the cycle.[8]
GABA is a very important neurotransmitter in animal brains, and a low concentration of GABA in mammalian brains has been linked to several neurological disorders, including Alzheimer's disease and Parkinson's disease.[9][10] Because GABA-T degrades GABA, the inhibition of this enzyme has been the target of many medical studies.[9] The goal of these studies is to find a way to inhibit GABA-T activity, which would reduce the rate that GABA and 2-oxoglutarate are converted to semialdehyde and L-glutamate, thus raising GABA concentration in the brain. There is also a genetic disorder in humans which can lead to a deficiency in GABA-T. This can lead to developmental impairment or mortality in extreme cases.[11]
In plants, GABA can be produced as a stress response.[5] Plants also use GABA to for internal signaling and for interactions with other organisms near the plant.[5] In all of these intra-plant pathways, GABA-T will take on the role of degrading GABA. It has also been demonstrated that the succinate produced in the GABA shunt makes up a significant proportion of the succinate needed by the mitochondrion.[12]
In fungi, the breakdown of GABA in the GABA shunt is key in ensuring a high level of activity in the critic acid cycle.[13] There is also experimental evidence that the breakdown of GABA by GABA-T plays a role in managing oxidative stress in fungi.[13]
Structural Studies
There have been several structures solved for this class of enzymes, given PDB accession codes, and published in peer-reviewed journals. At least 4 such structures have been solved using pig enzymes: 1OHV, 1OHW, 1OHY, 1SF2, and at least 4 such structures have been solved in Escherichia coli: 1SFF, 1SZK, 1SZS, 1SZU. There are actually some differences between the enzyme structure for these organisms. E. coli enzymes of GABA-T lack an iron-sulfur cluster that is found in the pig model.[14]
Active sites
Amino acid residues found in the active site of 4-aminobutyrate transaminase include Lys-329, which are found on each of the two subunits of the enzyme.[15] This site will also bind with a pyridoxal 5'- phosphate co-enzyme.[15]
In enzymology, a 4-hydroxyglutamate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, an acetylornithine transaminase (EC 2.6.1.11) is an enzyme that catalyzes the chemical reaction
In enzymology, an alanine-glyoxylate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, an aminolevulinate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a D-amino-acid transaminase is an enzyme that catalyzes the chemical reaction:
In enzymology, a diaminobutyrate-2-oxoglutarate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a diaminobutyrate-pyruvate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a dihydroxyphenylalanine transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a glycine transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a leucine transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a L-lysine 6-transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a N6-acetyl-beta-lysine transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a pyridoxamine-phosphate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a (S)-3-amino-2-methylpropionate transaminase is an enzyme that catalyzes the chemical reaction
In enzymology, a succinylornithine transaminase (EC 2.6.1.81) is an enzyme that catalyzes the chemical reaction
In enzymology, a taurine-2-oxoglutarate transaminase is an enzyme that catalyzes the chemical reaction.
In enzymology, a tryptophan transaminase is an enzyme that catalyzes the chemical reaction
In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system. Neurons are unable to synthesize either the excitatory neurotransmitter glutamate, or the inhibitory GABA from glucose. Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes. The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA.
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
4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene. This gene is located in chromosome 16 at position of 13.2. 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. 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids. ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa. 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.
↑ Cao J, Barbosa JM, Singh N, Locy RD (July 2013). "GABA transaminases from Saccharomyces cerevisiae and Arabidopsis thaliana complement function in cytosol and mitochondria". Yeast. 30 (7): 279–89. doi:10.1002/yea.2962. PMID23740823. S2CID1303165.
↑ Fait A, Fromm H, Walter D, Galili G, Fernie AR (January 2008). "Highway or byway: the metabolic role of the GABA shunt in plants". Trends in Plant Science. 13 (1): 14–9. doi:10.1016/j.tplants.2007.10.005. PMID18155636.
↑ Awad R, Muhammad A, Durst T, Trudeau VL, Arnason JT (August 2009). "Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity". Phytotherapy Research. 23 (8): 1075–81. doi:10.1002/ptr.2712. PMID19165747. S2CID23127112.
Aurich H (October 1961). "[On the beta-alanine-alpha-ketoglutarate transaminase from Neurospora crassa]" [On the beta-alanine-alpha-ketoglutarate transaminase from Neurospora crassa]. Hoppe-Seyler's Zeitschrift für Physiologische Chemie (in German). 326: 25–33. doi:10.1515/bchm2.1961.326.1.25. PMID13863304.
Schousboe A, Wu JY, Roberts E (July 1973). "Purification and characterization of the 4-aminobutyrate--2,ketoglutarate transaminase from mouse brain". Biochemistry. 12 (15): 2868–73. doi:10.1021/bi00739a015. PMID4719123.
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