Kynurenic acid

Kynurenic acid
IUPAC name 4-hydroxyquinoline-2-carboxylic acid
Other names Kinurenic acid, kynuronic acid, quinurenic acid, transtorine
Identifiers
CAS number	492-27-3 Y
PubChem	3845
ChemSpider	3712 Y
KEGG	C01717 Y
ChEBI	CHEBI:18344 Y
ChEMBL	CHEMBL299155 Y
Jmol-3D images	Image 1
SMILES O=C\2c1c(cccc1)NC(=C/2)/C(=O)O
InChI InChI=1S/C10H7NO3/c12-9-5-8(10(13)14)11-7-4-2-1-3-6(7)9/h1-5H,(H,11,12)(H,13,14) Y Key: HCZHHEIFKROPDY-UHFFFAOYSA-N Y InChI=1/C10H7NO3/c12-9-5-8(10(13)14)11-7-4-2-1-3-6(7)9/h1-5H,(H,11,12)(H,13,14) Key: HCZHHEIFKROPDY-UHFFFAOYAN
Properties
Molecular formula	C10H7NO3
Molar mass	189.168 g/mol
Melting point	282.5°C
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Kynurenic acid (KYNA or KYN) 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 neurophysiological and neuropathological 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.^[1]

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

Mechanism of action

KYNA has been proposed to act on four targets:

• As an antagonist at ionotropic AMPA, NMDA and Kainate glutamate receptors in the concentration range of 0.1-2.5 mM^[2]
• As a noncompetitive antagonist at the glycine site of the NMDA receptor.
• As an antagonist of the α7 nicotinic acetylcholine receptor.^[3] However, recently (2011) direct recording of α7 nicotinic acetylcholine receptor currents in adult (noncultured) hippocampal interneurons by the Cooper laboratory ^[4] validated a 2009 study ^[5] that failed to find any blocking effect of kynurenic acid across a wide range of concentrations, thus suggesting that in noncultured, intact preparations from adult animals there is no effect of kynurenic acid on α7 nicotinic acetylcholine receptor currents ^{[4] [5]}
• As a ligand for the orphan G protein-coupled receptor GPR35.^[6] Another tryptophan metabolite, 5-hydroxyindoleacetic acid exerts its effects via the orphan G protein-coupled receptor GPR35 ^[7]

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,^[8][9] 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. ^[10]

See also

• Xanthurenic acid

References

External links

• Link found between TBE and schizophrenia - TheLocal.se, Sweden's news in English, 6 November 2007.