Aminoadipate aminotransferase (Kynurenine aminotransferase 2) (KAT2)

Aminoadipate aminotransferase (Kynurenine aminotransferase 2) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the transamination of L-kynurenine to kynurenic acid (KYNA) and L-2-aminoadipate to 2-oxoadipate (UniProt P48431). In the central nervous system, it is the predominant isoform responsible for the synthesis of KYNA, an endogenous antagonist of N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α7nACh) receptors (PubMed: 21564050). Elevated brain levels of KYNA have been implicated in the pathophysiology of schizophrenia and cognitive impairment, as KYNA-mediated inhibition of these receptors reduces the release of key neurotransmitters like glutamate, dopamine, and acetylcholine (PubMed: 24564466). Consequently, KAT2 is a significant therapeutic target for the development of pro-cognitive agents. Small-molecule inhibitors, such as PF-04859989, aim to lower KYNA concentrations to restore normal neurotransmission and improve cognitive function in psychiatric and neurodegenerative disorders (PubMed: 26514401).

Other names

AADATKAT IIKAT2Kynurenine--oxoglutarate transaminase 2Kynurenine--oxoglutarate transaminase IIL-aminoadipate aminotransferaseAminoadipate aminotransferase, mitochondrial

Inhibition of kynurenine aminotransferase 2 to reduce the synthesis of kynurenic acid (KYNA), an endogenous antagonist of NMDA and alpha-7 nicotinic acetylcholine receptors, thereby enhancing glutamatergic, dopaminergic, and cholinergic neurotransmission.