Kynurenic acid
From Wikipedia, the free encyclopedia
| 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] |
| PubChem | |
| 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.
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.
Contents |
[edit] 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.[2]
- As a ligand for G protein-coupled receptor GPR35.[3]
[edit] 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.
[edit] See also
[edit] 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:. 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:. 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:. PMID 17573079.
- ^ Erhardt S, Schwieler L, Engberg G (2003). "Kynurenic acid and schizophrenia". Adv. Exp. Med. Biol. 527: 155–65. PMID 15206728.
[edit] External links
- Link found between TBE and schizophrenia - TheLocal.se, Sweden's news in English, 6th November 2007.
