4-aminobutyrate aminotransferase (GABA-T) (ABAT)

4-aminobutyrate aminotransferase (GABA-T) is a mitochondrial enzyme that serves as the primary catabolic pathway for gamma-aminobutyric acid (GABA), the central nervous system's chief inhibitory neurotransmitter (UniProt P80404). By catalyzing the transamination of GABA to succinic semialdehyde, it regulates the availability of GABA for synaptic transmission and maintains metabolic balance within the GABA shunt (PubMed PMID: 22133262). In clinical practice, GABA-T is a major therapeutic target for epilepsy, where increasing GABA levels helps counteract neuronal hyperexcitability (StatPearls, Vigabatrin). The drug Vigabatrin acts as a suicide inhibitor of this enzyme, effectively raising GABA concentrations in the brain to treat refractory seizures and infantile spasms (FDA Label, Sabril). However, the clinical utility of targeting GABA metabolism via GABA-T is limited by significant safety risks, most notably permanent peripheral visual field loss due to retinal accumulation of the drug or its metabolites (PubMed PMID: 15505134).

Other names

GABA transaminaseGABA-T4-aminobutyrate:2-oxoglutarate aminotransferaseL-glutamate:4-aminobutyrate aminotransferaseGamma-amino-butyrate transaminase

Irreversible inhibition of the enzyme responsible for GABA degradation, leading to increased synaptic and extra-synaptic GABA concentrations.