Gamma-Aminobutyric Acid Aminotransferase (GABA-T)

GABA aminotransferase (GABA-T), also known as 4-aminobutyrate transaminase, is a mitochondrial enzyme that catalyzes the degradation of GABA by transferring its amino group to α-ketoglutarate, producing succinic semialdehyde and L-glutamate. This reaction is part of the "GABA shunt," an alternative pathway for glutamate metabolism that links neurotransmitter turnover with energy production in the citric acid cycle. By degrading excess GABA after neurotransmission, this enzyme regulates inhibitory signaling in the brain and prevents excessive accumulation or depletion of this critical neurotransmitter. Selective inhibition of GABA-T increases brain levels of GABA and has therapeutic applications for epilepsy; vigabatrin is one such antiepileptic drug targeting this enzyme by irreversible inhibition. Mutations or deficiencies in ABAT can lead to neurological disorders due to disrupted inhibitory signaling. Crystal structures show that mammalian GABA-T functions as a dimer containing both PLP cofactors at each active site and an unusual [2Fe–2S] cluster whose function remains unclear but may relate to structural stability or regulation.

Other names

GABA transaminase4-Aminobutyrate transaminaseABAT

Irreversible inhibition of GABA-T, increasing brain levels of GABA