4-aminobutyrate aminotransferase and Succinate-semialdehyde dehydrogenase (GABA-T and SSADH)

GABA transaminase (GABA-T) and succinate semialdehyde dehydrogenase (SSADH) are the two primary enzymes responsible for the catabolism of gamma-aminobutyric acid (GABA) within the GABA shunt pathway (UniProt: P80404, P51649). GABA-T, encoded by the ABAT gene, converts GABA into succinate semialdehyde, which is then oxidized by SSADH, encoded by the ALDH5A1 gene, into succinate for use in the mitochondrial tricarboxylic acid cycle. This pathway is essential for regulating the levels of GABA, the brain's principal inhibitory neurotransmitter, and maintaining neuronal excitability balance. Pharmacologically, GABA-T is the primary target of the antiepileptic drug vigabatrin, which irreversibly inhibits the enzyme to elevate GABA levels and treat refractory seizures and infantile spasms (PubMed: 25163395). Genetic deficiencies in these enzymes lead to rare neurometabolic disorders; SSADH deficiency results in the accumulation of GABA and 4-hydroxybutyric acid (GHB), leading to developmental delay, hypotonia, and seizures (NIH: Genetic and Rare Diseases Information Center). Monitoring these metabolites is crucial for the diagnosis and management of these conditions.

Other names

GABA transaminaseABAT4-aminobutyrate aminotransferaseSuccinate-semialdehyde dehydrogenaseSSADHALDH5A1GABA-TGABA aminotransferase

Vigabatrin acts as a suicide inhibitor of GABA transaminase, forming a covalent bond with the enzyme to prevent GABA degradation, thereby increasing inhibitory tone in the CNS (StatPearls: Vigabatrin).