4-Aminobutyrate transaminase

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. 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 -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. This produces succinate semialdehyde and -glutamate. catalyzed by the enzyme 4-aminobutyrate—pyruvate transaminase: :(1) 4-aminobutanoate (GABA) + pyruvate succinate semialdehyde + -alanine : (2) 4-aminobutanoate (GABA) + glyoxylate succinate semialdehyde + glycine == Cellular and metabolic role ==

The primary role of GABA-T is to break down GABA as part of the GABA-Shunt. The critic acid cycle can then produce 2-oxoglutarate (α-ketoglutarate), which can be used to make glutamate, which can in turn be converted back into GABA, continuing the cycle. Because GABA-T degrades GABA, the inhibition of this enzyme has been the target of many medical studies. In plants, GABA can be produced as a stress response. In fungi, the breakdown of GABA in the GABA shunt is key in ensuring a high level of activity in the critic acid cycle. There is also experimental evidence that the breakdown of GABA by GABA-T plays a role in managing oxidative stress in fungi. == 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: , , , , 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. == 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. This site will also bind with a pyridoxal 5'􏰌- phosphate co-enzyme. == Inhibitors ==

• Aminooxyacetic acid • Gabaculine • Phenelzine • Phenylethylidenehydrazine (PEH) • Rosmarinic acid • Valproic acid • Vigabatrin == References ==