- Kynurenic acid
Chembox new
Name = Kynurenic acid
ImageFile = KynurenicAcid.png
IUPACName = 4-oxo-1H-quinoline-2-carboxylic acid
OtherNames = Kinurenic acid, kynuronic acid, quinurenic acid, transtorine
Section1 = Chembox Identifiers
CASNo = 492-27-3
PubChem = 3845
SMILES = C1=CC=C2C(=C1)C(=O)C=C(N2)C(=O)O
Section2 = Chembox Properties
Formula = C10H7N1O3
MolarMass = 189.168 g/mol
Density =
MeltingPt = 282.5°C
BoilingPt =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 andanticonvulsant , 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.Liebig, J., Uber Kynurensäure, "Justus Liebigs Ann. Chem.", 86: 125-126, 1853.]It is formed from L-
kynurenine in a reaction catalyzed by the enzymekynurenine—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 α7 nicotinic acetylcholine receptor. This action is contrary to another tryptophan metabolite,5-hydroxyindoleacetic acid . cite journal |author=Grilli M, Raiteri L, Patti L, Parodi M, Robino F, Raiteri M, Marchi M |title=Modulation of the function of presynaptic alpha7 and non-alpha7 nicotinic receptors by the tryptophan metabolites, 5-hydroxyindole and kynurenate in mouse brain |journal=Br. J. Pharmacol. |volume=149 |issue=6 |pages=724–32 |year=2006 |pmid=17016503 |doi=10.1038/sj.bjp.0706914]
* As a ligand forG protein-coupled receptor GPR35 . cite journal |author=Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L |title=Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35 |journal=J. Biol. Chem. |volume=281 |issue=31 |pages=22021–8 |year=2006 |pmid=16754668 |doi=10.1074/jbc.M603503200]Role in disease
High levels of kynurenic acid have been identified in patients suffering from
tick-borne encephalitis ,schizophrenia andHIV -related illnesses. In all these situations increased levels were associated with confusion and psychotic symptoms. Kynurenic acid acts in thebrain as a glycine-site NMDAr antagonist, key in glutamatergic neurotransmission system, which is thought to be involved in thepathophysiology andpathogenesis of schizophrenia.A kynurenic acid hypothesis of schizophrenia has been proposed in 2007,cite journal |author=Erhardt S, Schwieler L, Nilsson L, Linderholm K, Engberg G |title=The kynurenic acid hypothesis of schizophrenia |journal=Physiol. Behav. |volume=92 |issue=1-2 |pages=203–9 |year=2007 |pmid=17573079 |doi=10.1016/j.physbeh.2007.05.025] cite journal |author=Erhardt S, Schwieler L, Engberg G |title=Kynurenic acid and schizophrenia |journal=Adv. Exp. Med. Biol. |volume=527 |issue= |pages=155–65 |year=2003 |pmid=15206728 |doi = ] 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 ofkynureninase .ee also
*
Xanthurenic acid References
External links
* [http://www.thelocal.se/9013/20071106/ Link found between TBE and schizophrenia] - TheLocal.se, Sweden's news in English, 6th November 2007.
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