4-aminobutyrate aminotransferase (ABAT) (ABAT)

4-aminobutyrate aminotransferase (ABAT), frequently referred to as GABA transaminase, is the key mitochondrial enzyme responsible for the catabolism of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system [1][2]. The enzyme catalyzes the conversion of GABA and alpha-ketoglutarate into succinate semialdehyde and L-glutamate, a reaction that requires pyridoxal 5'-phosphate (PLP) as a cofactor [2][3]. By regulating the metabolic breakdown of GABA, ABAT plays a fundamental role in maintaining the delicate balance between neuronal excitation and inhibition [4]. In clinical practice, ABAT is a major therapeutic target for the treatment of seizure disorders; its inhibition leads to a significant increase in brain GABA levels, which suppresses hyperexcitability [3][5]. The drug vigabatrin is a well-known irreversible inhibitor of ABAT used specifically for refractory complex partial seizures and infantile spasms [5][6]. However, the use of drugs targeting this enzyme is often limited by serious safety concerns, most notably permanent retinal toxicity and associated visual field loss [3][6].

Other names

GABA transaminaseGABA-T4-aminobutyrate transaminaseL-glutamate:4-aminobutyrate aminotransferaseGABATGamma-amino-butyrate transaminase

Irreversible inhibition of 4-aminobutyrate aminotransferase, which prevents the degradation of GABA into succinate semialdehyde, thereby increasing the concentration of GABA in the synaptic cleft and enhancing inhibitory neurotransmission.