GABATransaminase

GABA transaminase (GABA-T), also known as 4-aminobutyrate aminotransferase, is a mitochondrial enzyme that catalyzes the reversible transamination of the inhibitory neurotransmitter GABA with 2-oxoglutarate, yielding succinic semialdehyde and glutamate. The enzyme is pyridoxal phosphate (PLP)-dependent and is encoded by the ABAT gene in humans.

Primarily expressed in brain tissue, GABA-T is found in both neurons and astrocytes and is a component of the GABA shunt, a metabolic route that maintains GABA homeostasis and provides substrates for the TCA cycle. As a PLP-dependent aminotransferase, it operates via a typical Schiff base mechanism, forming a covalent intermediate with GABA.

By regulating GABA levels, GABA-T contributes to the termination of GABAergic signaling and helps balance excitatory and inhibitory neurotransmission. The produced glutamate can be further metabolized, while succinic semialdehyde is oxidized to succinate and enters the tricarboxylic acid cycle.

Pharmacologically, inhibition of GABA-T increases brain GABA levels. The irreversible inhibitor vigabatrin is used to treat refractory epilepsy and infantile spasms, but carries risk of retinal toxicity and visual field loss with long-term use. Inherited deficiency of GABA-T (GABA transaminase deficiency), usually due to ABAT mutations, is a rare metabolic disorder characterized by developmental delay, hypotonia, and seizures.

Species differences, regulatory mechanisms, and potential therapeutic implications continue to be studied. GABA-T activity is commonly measured in diagnostic assays for metabolic disorders, and the enzyme remains a focus in epilepsy research as a target to modulate GABAergic transmission.