Kynurenine aminotransferase (KAT)

Kynurenine aminotransferase refers to a family of pyridoxal 5′-phosphate-dependent enzymes (KAT I–IV) that catalyze the irreversible transamination of L-kynurenine to kynurenic acid (KYNA) as part of the kynurenine pathway of tryptophan metabolism in mammals[2][3][4]. KYNA is an endogenous antagonist of the NMDA and α7-nicotinic acetylcholine receptors, thereby modulating glutamatergic neurotransmission and exerting neuroprotective effects[2][4]. Multiple KAT isoforms exist in different tissues and cellular compartments (e.g., cytosolic or mitochondrial), each with distinct substrate specificity and structural features[2][3]. Abnormal activity or expression of KAT enzymes alters KYNA levels and has implications in the pathophysiology of schizophrenia, Alzheimer’s disease, and other neurological disorders where KYNA is implicated as both potentially neuroprotective and neurotoxic, depending on context and location[2][3][4]. The KAT enzymes thus represent potential therapeutic targets for modulating KYNA levels and altering disease risk or progression in various CNS and systemic disorders.

Other names

KATKynurenine transaminaseKynurenine–glyoxylate aminotransferaseGlutamine transaminase K (KAT I)Aminoadipate aminotransferase (KAT II)Cysteine conjugate beta-lyase 1 (KAT I)Cysteine conjugate beta-lyase 2 (KAT III)Glutamic-oxaloacetic transaminase 2 / mitochondrial aspartate aminotransferase (KAT IV)KYATKynurenine aminotransferase I, II, III, IV (for isoforms)

Inhibition of KATs reduces kynurenic acid (KYNA) production, which could affect glutamatergic and cholinergic signaling and synaptic transmission[2][3][4]. The mechanism for experimental inhibitors typically involves competitive or non-competitive binding to the enzyme active site, blocking transamination of kynurenine to kynurenic acid.