4-aminobutyrate aminotransferase (GABA-AT) (GABA-AT)

4-aminobutyrate aminotransferase (GABA-AT) is a key mitochondrial enzyme responsible for the catabolism of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the human central nervous system (UniProt P80404). It catalyzes the conversion of GABA and alpha-ketoglutarate into succinic semialdehyde and L-glutamate, utilizing pyridoxal 5'-phosphate as a cofactor (NCBI Gene ID 18). By regulating the degradation of GABA, this enzyme plays a pivotal role in maintaining neuronal excitability and synaptic homeostasis (PubMed: 22123472). In clinical practice, GABA-AT is a primary therapeutic target for the treatment of refractory epilepsy and infantile spasms, where increasing GABA levels helps suppress abnormal electrical activity (StatPearls: Vigabatrin). The most prominent drug targeting this enzyme is Vigabatrin, an irreversible suicide inhibitor that binds covalently to the active site (PubChem CID 5665). Beyond epilepsy, research suggests GABA-AT involvement in neurodegenerative conditions like Alzheimer's disease and certain types of cancer, where metabolic reprogramming occurs (PubMed: 30554105). However, chronic inhibition of GABA-AT is associated with serious safety risks, most notably permanent peripheral vision loss due to retinal toxicity (FDA Label: Sabril).

Other names

ABATGABA transaminaseGamma-aminobutyrate transaminaseGABATL-glutamate:4-aminobutyrate aminotransferase

Irreversible suicide inhibition of the enzyme, preventing the breakdown of GABA and increasing its concentration in the brain (PubChem CID 5665).