1.0 2011-09-21 00:09:59 UTC 2024-11-29 22:25:41 UTC FDB022200 Kynurenic acid Kynurenic 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-hydroxyquinoline 4-Hydroxy-2-chinolincarbonsaeure 4-Hydroxy-2-quinolinecarboxylate 4-hydroxy-2-Quinolinecarboxylic acid 4-hydroxy-Quinaldate 4-hydroxy-Quinaldic acid 4-Hydroxyquinaldate 4-Hydroxyquinaldic acid 4-Hydroxyquinaldinate 4-Hydroxyquinaldinic acid 4-Hydroxyquinoline-2-carboxylate 4-Hydroxyquinoline-2-carboxylic acid Kynurenate Kynurenic acid Kynurensaeure Quinurenic acid C10H7NO3 189.1675 189.042593095 4-oxo-1,4-dihydroquinoline-2-carboxylic acid acid, kynurenic 492-27-3 OC(=O)C1=CC(=O)C2=CC=CC=C2N1 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) 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 acids Organic compounds Organoheterocyclic compounds Quinolines and derivatives Quinoline carboxylic acids Aromatic heteropolycyclic compounds Azacyclic compounds Benzenoids Carboxylic acids Heteroaromatic compounds Hydrocarbon derivatives Hydroquinolines Hydroquinolones Monocarboxylic acids and derivatives Organic oxides Organonitrogen compounds Organooxygen compounds Organopnictogen compounds Pyridinecarboxylic acids Vinylogous amides Aromatic heteropolycyclic compound Azacycle Benzenoid Carboxylic acid Carboxylic acid derivative Dihydroquinoline Dihydroquinolone Heteroaromatic compound Hydrocarbon derivative Monocarboxylic acid or derivatives Organic nitrogen compound Organic oxide Organic oxygen compound Organonitrogen compound Organooxygen compound Organopnictogen compound Pyridine Pyridine carboxylic acid Pyridine carboxylic acid or derivatives Quinoline-2-carboxylic acid Vinylogous amide monohydroxyquinoline quinolinemonocarboxylic acid Solid logp 1.16 ALOGPS logs -2.30 ALOGPS solubility 9.54e-01 g/l ALOGPS logp 1.58 ChemAxon pka_strongest_acidic 3.17 ChemAxon pka_strongest_basic -4.4 ChemAxon iupac 4-oxo-1,4-dihydroquinoline-2-carboxylic acid ChemAxon average_mass 189.1675 ChemAxon mono_mass 189.042593095 ChemAxon smiles OC(=O)C1=CC(=O)C2=CC=CC=C2N1 ChemAxon formula C10H7NO3 ChemAxon 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) ChemAxon inchikey HCZHHEIFKROPDY-UHFFFAOYSA-N ChemAxon polar_surface_area 66.4 ChemAxon refractivity 52.32 ChemAxon polarizability 18.05 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Tryptophan Metabolism SMP00063 map00380 Metabolism and Physiological Effects of Kynurenic Acid SMP0123300 Specdb::NmrTwoD 1441 Specdb::NmrOneD 1495 Specdb::NmrOneD 2397 Specdb::NmrOneD 5073 Specdb::NmrOneD 5074 Specdb::MsIr 10 Specdb::MsIr 43 Specdb::MsIr 67 Specdb::MsIr 778 Specdb::MsIr 779 Specdb::MsIr 780 Specdb::CMs 622 Specdb::CMs 1769 Specdb::CMs 2817 Specdb::CMs 30096 Specdb::CMs 30586 Specdb::CMs 31206 Specdb::CMs 31852 Specdb::CMs 37715 Specdb::CMs 146067 Specdb::CMs 1072713 Specdb::CMs 1072714 Specdb::CMs 1072716 Specdb::MsMs 999 Specdb::MsMs 1000 Specdb::MsMs 1001 Specdb::MsMs 4503 Specdb::MsMs 4504 Specdb::MsMs 178914 Specdb::MsMs 178915 Specdb::MsMs 178916 Specdb::MsMs 181239 Specdb::MsMs 181240 Specdb::MsMs 181241 Specdb::MsMs 374620 Specdb::MsMs 437031 Specdb::MsMs 437032 Specdb::MsMs 437033 Specdb::MsMs 437034 Specdb::MsMs 437035 Specdb::MsMs 439248 Specdb::MsMs 439693 Specdb::MsMs 439694 Specdb::MsMs 440135 Specdb::MsMs 445144 Specdb::MsMs 445145 Specdb::MsMs 445146 Specdb::MsMs 445147 HMDB00715 18344 KYA #<Reference:0x000055ac3ffb1c60> #<Reference:0x000055ac3ffb1a58> #<Reference:0x000055ac3ffb1850> #<Reference:0x000055ac3ffb1670> #<Reference:0x000055ac3ffb13f0> #<Reference:0x000055ac3ffb0f68> #<Reference:0x000055ac3ffb0d88> #<Reference:0x000055ac3ffb0b30> #<Reference:0x000055ac3ffb08d8> #<Reference:0x000055ac3ffb05b8> #<Reference:0x000055ac3ffb0310> #<Reference:0x000055ac3ffb0130> #<Reference:0x000055ac3ff9fe20> #<Reference:0x000055ac3ff9fb28> #<Reference:0x000055ac3ff9f7b8> #<Reference:0x000055ac3ff9f420> #<Reference:0x000055ac3ff9f128> #<Reference:0x000055ac3ff9ec28> Anatidae Type 1 specific Anatidae 8830 Beefalo Type 1 specific Bos taurus X Bison bison 297284 Bison Type 1 specific Bison bison 9901 Buffalo Type 1 specific Bubalus bubalis 89462 Cattle (Beef, Veal) Type 1 specific Bos taurus 9913 Chicken Type 1 specific Gallus gallus 9031 Columbidae (Dove, Pigeon) Type 1 specific Columbidae 8930 Deer Type 1 specific Cervidae 9850 Domestic goat Type 1 specific Capra aegagrus hircus 9925 Domestic pig Type 1 specific Sus scrofa domestica 9825 Elk Type 1 specific Cervus canadensis 1574408 Emu Type 1 specific Dromaius novaehollandiae 8790 European rabbit Type 1 specific Oryctolagus 9984 Greylag goose Type 1 specific Anser anser 8843 Guinea hen Type 1 specific Numida meleagris 8996 Horse Type 1 specific Equus caballus 9796 Mallard duck Type 1 specific Anas platyrhynchos 8839 Mountain hare Type 1 specific Lepus timidus 62621 Mule deer Type 1 specific Odocoileus 9871 Ostrich Type 1 specific Struthio camelus 8801 Pheasant Type 1 specific Phasianus colchicus 9054 Quail Type 1 specific Phasianidae 9005 Rabbit Type 1 specific Leporidae 9979 Rock ptarmigan Type 1 specific Lagopus muta 64668 Sheep (Mutton, Lamb) Type 1 specific Ovis aries 9940 Squab Type 1 specific Columba 8931 Turkey Type 1 specific Meleagris gallopavo 9103 Velvet duck Type 1 specific Melanitta fusca 371864 Wild boar Type 1 specific Sus scrofa 9823 Kynurenine--oxoglutarate transaminase 1 Q16773 CCBL1 Kynurenine--oxoglutarate transaminase 3 Q6YP21 CCBL2