1.02011-09-21 00:09:59 UTC2015-10-09 22:28:01 UTCFDB022200Kynurenic acidKynurenic acid (KYNA) is a well-known endogenous antagonist of the glutamate ionotropic excitatory amino acid receptors N-methyl-D-aspartate (NMDA), alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptors and of the nicotine cholinergic subtype alpha 7 receptors. KYNA neuroprotective and anticonvulsive activities have been demonstrated in animal models of neurodegenerative diseases. Because of KYNA's neuromodulatory character, its involvement has been speculatively linked to the pathogenesis of a number of neurological conditions including those in the ageing process. Different patterns of abnormalities in various stages of KYNA metabolism in the CNS have been reported in Alzheimer's disease, Parkinson's disease and Huntington's disease. In HIV-1-infected patients and in patients with Lyme neuroborreliosis a marked rise of KYNA metabolism was seen. In the ageing process KYNA metabolism in the CNS of rats shows a characteristic pattern of changes throughout the life span. A marked increase of the KYNA content in the CNS occurs before the birth, followed by a dramatic decline on the day of birth. A low activity was seen during ontogenesis, and a slow and progressive enhancement occurs during maturation and ageing. This remarkable profile of KYNA metabolism alterations in the mammalian brain has been suggested to result from the development of the organisation of neuronal connections and synaptic plasticity, development of receptor recognition sites, maturation and ageing. There is significant evidence that KYNA can improve cognition and memory, but it has also been demonstrated that it interferes with working memory. Impairment of cognitive function in various neurodegenerative disorders is accompanied by profound reduction and/or elevation of KYNA metabolism. The view that enhancement of CNS KYNA levels could underlie cognitive decline is supported by the increased KYNA metabolism in Alzheimer's disease, by the increased KYNA metabolism in down's syndrome and the enhancement of KYNA function during the early stage of Huntington's disease. Kynurenic acid is the only endogenous N-methyl-D-aspartate (NMDA) receptor antagonist identified up to now, that mediates glutamatergic hypofunction. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. Despite the NMDA receptor antagonism, kynurenic acid also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased kynurenic acid levels can explain psychotic symptoms and cognitive deterioration. Kynurenic acid levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. (PMID: 17062375, 16088227) [HMDB]2-Carboxy-4-hydroxyquinoline4-Hydroxy-2-chinolincarbonsaeure4-Hydroxy-2-quinolinecarboxylate4-hydroxy-2-Quinolinecarboxylic acid4-hydroxy-Quinaldate4-hydroxy-Quinaldic acid4-Hydroxyquinaldate4-Hydroxyquinaldic acid4-Hydroxyquinaldinate4-Hydroxyquinaldinic acid4-Hydroxyquinoline-2-carboxylate4-Hydroxyquinoline-2-carboxylic acidKynurenateKynurenic acidKynurensaeureQuinurenic acidC10H7NO3189.1675189.0425930954-oxo-1,4-dihydroquinoline-2-carboxylic acidacid, kynurenic492-27-3OC(=O)C1=CC(=O)C2=CC=CC=C2N1InChI=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)HCZHHEIFKROPDY-UHFFFAOYSA-N belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.Quinoline carboxylic acidsOrganic compoundsOrganoheterocyclic compoundsQuinolines and derivativesQuinoline carboxylic acidsAromatic heteropolycyclic compoundsAzacyclic compoundsBenzenoidsCarboxylic acidsHeteroaromatic compoundsHydrocarbon derivativesHydroquinolinesHydroquinolonesMonocarboxylic acids and derivativesOrganic oxidesOrganonitrogen compoundsOrganooxygen compoundsOrganopnictogen compoundsPyridinecarboxylic acidsVinylogous amidesAromatic heteropolycyclic compoundAzacycleBenzenoidCarboxylic acidCarboxylic acid derivativeDihydroquinolineDihydroquinoloneHeteroaromatic compoundHydrocarbon derivativeMonocarboxylic acid or derivativesOrganic nitrogen compoundOrganic oxideOrganic oxygen compoundOrganonitrogen compoundOrganooxygen compoundOrganopnictogen compoundPyridinePyridine carboxylic acidPyridine carboxylic acid or derivativesQuinoline-2-carboxylic acidVinylogous amidemonohydroxyquinolinequinolinemonocarboxylic acidSolidlogp1.16logs-2.30solubility9.54e-01 g/llogp1.58pka_strongest_acidic3.17pka_strongest_basic-4.4iupac4-oxo-1,4-dihydroquinoline-2-carboxylic acidaverage_mass189.1675mono_mass189.042593095smilesOC(=O)C1=CC(=O)C2=CC=CC=C2N1formulaC10H7NO3inchiInChI=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)inchikeyHCZHHEIFKROPDY-UHFFFAOYSA-Npolar_surface_area66.4refractivity52.32polarizability18.05rotatable_bond_count1acceptor_count4donor_count2physiological_charge-1formal_charge0Tryptophan MetabolismSMP00063map00380Specdb::NmrTwoD1441Specdb::NmrOneD1495Specdb::NmrOneD2397Specdb::NmrOneD5073Specdb::NmrOneD5074Specdb::MsIr10Specdb::MsIr43Specdb::MsIr67Specdb::MsIr778Specdb::MsIr779Specdb::MsIr780Specdb::CMs622Specdb::CMs1769Specdb::CMs2817Specdb::CMs30096Specdb::CMs30586Specdb::CMs31206Specdb::CMs31852Specdb::CMs37715Specdb::CMs146067Specdb::CMs1072713Specdb::CMs1072714Specdb::CMs1072716Specdb::MsMs999Specdb::MsMs1000Specdb::MsMs1001Specdb::MsMs4503Specdb::MsMs4504Specdb::MsMs178914Specdb::MsMs178915Specdb::MsMs178916Specdb::MsMs181239Specdb::MsMs181240Specdb::MsMs181241Specdb::MsMs374620Specdb::MsMs437031Specdb::MsMs437032Specdb::MsMs437033Specdb::MsMs437034Specdb::MsMs437035Specdb::MsMs439248Specdb::MsMs439693Specdb::MsMs439694Specdb::MsMs440135Specdb::MsMs445144Specdb::MsMs445145Specdb::MsMs445146Specdb::MsMs445147HMDB0071518344KYA#<Reference:0x00005556742e8018>#<Reference:0x00005556742e38b0>#<Reference:0x00005556742e32c0>#<Reference:0x00005556742e2c58>#<Reference:0x00005556742e27a8>#<Reference:0x00005556742e2258>#<Reference:0x00005556742e1ce0>#<Reference:0x00005556742e1768>#<Reference:0x00005556742e12e0>#<Reference:0x00005556742e0d90>#<Reference:0x00005556742e0818>#<Reference:0x00005556742e0200>#<Reference:0x00005556742dfc88>#<Reference:0x00005556742df738>#<Reference:0x00005556742df148>#<Reference:0x00005556742de9a0>#<Reference:0x00005556742de4f0>#<Reference:0x00005556742ddf00>AnatidaeType 1specificAnatidae8830BeefaloType 1specificBos taurus X Bison bison297284BisonType 1specificBison bison9901BuffaloType 1specificBubalus bubalis89462Cattle (Beef, Veal)Type 1specificBos taurus9913ChickenType 1specificGallus gallus9031Columbidae (Dove, Pigeon)Type 1specificColumbidae8930DeerType 1specificCervidae9850Domestic goatType 1specificCapra aegagrus hircus9925Domestic pigType 1specificSus scrofa domestica9825ElkType 1specificCervus canadensis1574408EmuType 1specificDromaius novaehollandiae8790European rabbitType 1specificOryctolagus9984Greylag gooseType 1specificAnser anser8843Guinea henType 1specificNumida meleagris8996HorseType 1specificEquus caballus9796Mallard duckType 1specificAnas platyrhynchos8839Mountain hareType 1specificLepus timidus62621Mule deerType 1specificOdocoileus9871OstrichType 1specificStruthio camelus8801PheasantType 1specificPhasianus colchicus9054QuailType 1specificPhasianidae9005RabbitType 1specificLeporidae9979Rock ptarmiganType 1specificLagopus muta64668Sheep (Mutton, Lamb)Type 1specificOvis aries9940SquabType 1specificColumba8931TurkeyType 1specificMeleagris gallopavo9103Velvet duckType 1specificMelanitta fusca371864Wild boarType 1specificSus scrofa9823Kynurenine--oxoglutarate transaminase 1Q16773CCBL1Kynurenine--oxoglutarate transaminase 3Q6YP21CCBL2