4-aminobutyrate aminotransferase, mitochondrial

ABAT (4-aminobutyrate aminotransferase, mitochondrial) is a mitochondrial enzyme that catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to their respective semialdehyde products, including succinate semialdehyde. This transamination reaction is central to GABA catabolism and the conversion of non-protein amino acids (UniProt: P80404).

Loss-of-function mutations in ABAT cause GABA-transaminase deficiency (GABATD, MIM 613163), a rare autosomal recessive disorder characterized by psychomotor retardation, hypotonia, seizures, and EEG abnormalities. The enzyme's role in GABA metabolism positions it at the intersection of neurotransmitter homeostasis and energy metabolism (UniProt: P80404).

ABAT is upregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain relative to age-matched controls by TMT-labeled proteomics across four subcellular fractions showed ABAT elevation with a mean log2 fold-change of +0.32 (Chaparral AD proteomics). This upregulation suggests altered GABAergic signaling or metabolic compensation in the AD brain, though the functional consequence remains to be determined.