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Kynurenic acid

Kynurenic acid

IUPAC name	4-oxo-1H-quinoline-2-carboxylic acid
Other names	Kinurenic acid, kynuronic acid, quinurenic acid, transtorine
Identifiers
CAS number	492-27-3
SMILES	C1=CC=C2C(=C1)C(=O)C=C(N2)C(=O)O
Properties
Molecular formula	C₁₀H₇N₁O₃
Molar mass	189.168 g/mol
Melting point	282.5°C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

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.

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Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig in dog urine.^[1]

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

Mechanism of action

KYNA was found to act on three receptors:

As a noncompetitive antagonist at glycine site of the NMDA receptor.
As an antagonist of alpha7 nicotinic receptor. This action is contrary to another tryptophan metabolite, 5-hydroxyindoleacetic acid.^[2]

As a ligand for G protein-coupled receptor GPR35.^[3]

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,^[4]^[5] 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.

References

^ Liebig, J., Uber Kynurensäure, Justus Liebigs Ann. Chem., 86: 125-126, 1853.
^ Grilli M, Raiteri L, Patti L, Parodi M, Robino F, Raiteri M, Marchi M (2006). "Modulation of the function of presynaptic alpha7 and non-alpha7 nicotinic receptors by the tryptophan metabolites, 5-hydroxyindole and kynurenate in mouse brain". Br. J. Pharmacol. 149 (6): 724–32. doi:10.1038/sj.bjp.0706914. PMID 17016503.
^ Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L (2006). "Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35". J. Biol. Chem. 281 (31): 22021–8. doi:10.1074/jbc.M603503200. PMID 16754668.
^ Erhardt S, Schwieler L, Nilsson L, Linderholm K, Engberg G (2007). "The kynurenic acid hypothesis of schizophrenia". Physiol. Behav. 92 (1-2): 203–9. doi:10.1016/j.physbeh.2007.05.025. PMID 17573079.
^ Erhardt S, Schwieler L, Engberg G (2003). "Kynurenic acid and schizophrenia". Adv. Exp. Med. Biol. 527: 155–65. PMID 15206728.

Categories: Aromatic acids | Quinolines | NMDA receptor antagonists

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Kynurenic_acid". A list of authors is available in Wikipedia.