kynurenic acid

  • Name: kynurenic acid
  • Description: 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-propion... ic 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. (SOURCE: PMID: 17062375; PMID:16088227; HMDB0000715)
Overview of age-variations
Age group comparisons
PMID Age/Age interval, Gender Value (unit of measurement) Method Sample
16088227 Age 35.4 ± 2.2, ranging from 25 to 50 years, Gender ⚥ 2.84 (fmol/microL) HPLC cerebrospinal fluid
16088227 Age 61.6 ± 3.3 years, ranging from 50 to 74, Gender ⚥ 4.09 (fmol/microL) HPLC cerebrospinal fluid
Linear regression
PMID Age/Age interval, Gender Value (unit of measurement) Method Sample
log2 ratio/log2(FC)
PMID Age/Age interval, Gender Value (unit of measurement) Method Sample
26088811 Age 40.9 ± 10.3, Gender ⚥ -0.63 (log2 ratio) UHPLC negative mode urine
  • Synonym:
    4-Hydroxy-2-quinolinecarboxylic acid;4-hydroxyquinaldinic acid; 4-hydroxyquinaldic acid;4-hydroxy-2-chinolincarbonsaeure
  • Chemical Formula:
  • Systematic name:
    4-oxo-1,4-dihydroquinoline-2-carboxylic acid
  • InChI:
  • InChI Key:
  • CAS number:
Pathway info P = product of S = substrate of
Metabolite sources and localization
  • Metabolite location:
    Human organism, Body part, Human body biofluids, Biofluid tissues, Blood, Cerebrospinal fluid, Urine, Organ, Brain, Skin, Skin tissue, Epidermis, Tissue, Connective tissue, Connective tissue cell, Fibroblast, Cellular (general class), Subcellular, Cytoplasm, Excreta material, Feces
  • Metabolite source:
    Homo sapiens, endogenous metabolite
Age group comparisons
Method: HPLC
Sample: cerebrospinal fluid
PubMed PMID: 16088227

Fold-change with age
Method: UHPLC negative mode
Sample: urine
PubMed PMID: 26088811