| 4-aminobutyrate transaminase | |
| Ec Number: | 2.6.1.19 |
| Cas Number: | 9037-67-6 |
| Go Code: | 0003867 |
| Width: | 270 |
| 4-aminobutyrate transaminase | |
| Hgncid: | 23 |
| Symbol: | ABAT |
| Entrezgene: | 18 |
| Omim: | 137150 |
| Refseq: | NM_020686 |
| Uniprot: | P80404 |
| Chromosome: | 16 |
| Arm: | p |
| Band: | 13.2 |
In enzymology, 4-aminobutyrate transaminase, also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction:
4-aminobutanoate + 2-oxoglutarate
\rightleftharpoons
Thus, the two substrates of this enzyme are 4-aminobutanoate (GABA) and 2-oxoglutarate. The two products are succinate semialdehyde and L-glutamate.
This enzyme belongs to the family of transferases, specifically the transaminases, which transfer nitrogenous groups. The systematic name of this enzyme class is 4-aminobutanoate:2-oxoglutarate aminotransferase. This enzyme participates in 5 metabolic pathways: alanine and aspartate metabolism, glutamate metabolism, beta-alanine metabolism, propanoate metabolism, and butanoate metabolism. It employs one cofactor, pyridoxal phosphate.
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]
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.
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. In plants, pyruvate and glyoxylate can be used in the place of 2-oxoglutarate.[7] catalyzed by the enzyme 4-aminobutyrate—pyruvate transaminase:
(1) 4-aminobutanoate (GABA) + pyruvate succinate semialdehyde + L-alanine
(2) 4-aminobutanoate (GABA) + glyoxylate succinate semialdehyde + glycine
The primary role of GABA-T is to break down GABA as part of the GABA-Shunt. 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.
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. 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. Plants also use GABA to for internal signaling and for interactions with other organisms near the plant. 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.
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:,,,, and at least 4 such structures have been solved in Escherichia coli:,,, . 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]
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.
See main article: GABA transaminase inhibitor.