Kynurenic acid

Kynurenic acid (KYNA) is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.

Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig in dog urine, which it was apparently named after.

It is formed from L-kynurenine in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.

Mechanism of action
KYNA has been found to act on three receptors:


 * As a noncompetitive antagonist at the glycine site of the NMDA receptor.
 * As an antagonist of the α7 nicotinic acetylcholine receptor. This action has been recently disputed and if true is contrary to another tryptophan metabolite, 5-hydroxyindoleacetic acid.

Role in disease
High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophrenia and HIV-related illnesses. In all these situations increased levels were associated with confusion and psychotic symptoms. Kynurenic acid acts in the brain as a glycine-site NMDAr antagonist, key in glutamatergic neurotransmission system, which is thought to be involved in the pathophysiology and pathogenesis of schizophrenia.

A kynurenic acid hypothesis of schizophrenia has been proposed in 2007, based on its action on midbrain dopamine activity and NMDArs, thus linking dopamine hypothesis of schizophrenia with the glutamate hypothesis of the disease.

High levels of kynurenic acid have been identified in human urine in certain metabolic disorders, such as marked pyridoxine deficiency and deficiency/absence of kynureninase.

When researchers decreased the levels of kynurenic acid in the brains of mice, the cognition was shown to improve markedly.