• Quinolinic acid (abbreviated QUIN or QA), also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. (wikipedia.org)
  • Quinolinic acid is a downstream product of the kynurenine pathway, which metabolizes the amino acid tryptophan. (wikipedia.org)
  • Quinolinic acid has a potent neurotoxic effect. (wikipedia.org)
  • Studies have demonstrated that quinolinic acid may be involved in many psychiatric disorders, neurodegenerative processes in the brain, as well as other disorders. (wikipedia.org)
  • Within the brain, quinolinic acid is only produced by activated microglia and macrophages. (wikipedia.org)
  • In 1949 L. Henderson was one of the earliest to describe quinolinic acid. (wikipedia.org)
  • Lapin followed up this research by demonstrating that quinolinic acid could induce convulsions when injected into mice brain ventricles. (wikipedia.org)
  • However, it was not until 1981 that Stone and Perkins showed that quinolinic acid activates the N-methyl-D-aspartate receptor (NMDAR). (wikipedia.org)
  • After this, Schwarcz demonstrated that elevated quinolinic acid levels could lead to axonal neurodegeneration. (wikipedia.org)
  • One of the earliest reported syntheses of this quinolinic acid was by Zdenko Hans Skraup, who found that methyl-substituted quinolines could be oxidized to quinolinic acid by potassium permanganate. (wikipedia.org)
  • Quinolinic acid may undergo further decarboxylation to nicotinic acid (niacin): Oxidation of aspartate by the enzyme aspartate oxidase gives iminosuccinate, containing the two carboxylic acid groups that are found in quinolinic acid. (wikipedia.org)
  • Condensation of iminosuccinate with glyceraldehyde-3-phosphate, mediated by quinolinate synthase, affords quinolinic acid. (wikipedia.org)
  • Quinolinic acid is a byproduct of the kynurenine pathway, which is responsible for catabolism of tryptophan in mammals. (wikipedia.org)
  • The quinolinic acid produced in microglia is then released and stimulates NMDA receptors, resulting in excitatory neurotoxicity. (wikipedia.org)
  • While astrocytes do not produce quinolinic acid directly, they do produce KYNA, which when released from the astrocytes can be taken in by migroglia that can in turn increase quinolinic acid production. (wikipedia.org)
  • Microglia and macrophages produce the vast majority of quinolinic acid present in the body. (wikipedia.org)
  • Under inflammatory conditions and conditions of T cell activation, leukocytes are retained in the brain by cytokine and chemokine production, which can lead to the breakdown of the BBB, thus increasing the quinolinic acid that enters the brain. (wikipedia.org)
  • Furthermore, quinolinic acid has been shown to play a role in destabilization of the cytoskeleton within astrocytes and brain endothelial cells, contributing to the degradation of the BBB, which results in higher concentrations of quinolinic acid in the brain. (wikipedia.org)
  • Quinolinic acid is an excitotoxin in the CNS. (wikipedia.org)
  • High levels of quinolinic acid can lead to hindered neuronal function or even apoptotic death. (wikipedia.org)
  • Quinolinic acid produces its toxic effect through several mechanisms, primarily as its function as an NMDA receptor agonist, which triggers a chain of deleterious effects, but also through lipid peroxidation, and cytoskeletal destabilization. (wikipedia.org)
  • The gliotoxic effects of quinolinic acid further amplify the inflammatory response. (wikipedia.org)
  • Quinolinic acid affects neurons located mainly in the hippocampus, striatum, and neocortex, due to the selectivity toward quinolinic acid by the specific NMDA receptors residing in those regions. (wikipedia.org)
  • When inflammation occurs, quinolinic acid is produced in excessive levels through the kynurenine pathway. (wikipedia.org)
  • BACKGROUND AND AIMS: Quinolinic acid (QA) is a metabolite of the kynurenine pathway, which is activated by inflammatory stimuli during viral infection. (bvsalud.org)
  • Tryptophan (TRP) is an essential dietary amino acid that, unless otherwise committed to protein synthesis, undergoes metabolism via the Tryptophan-Kynurenine (TRP-KYN) pathway in vertebrate organisms. (mdpi.com)
  • It is suspected that this is a result of activation of indoleamine dioxygenases (to be specific, IDO-1 and IDO-2) as well as tryptophan 2,3-dioxygenase (TDO) stimulation by inflammatory cytokines (mainly IFN-gamma, but also IFN-beta and IFN-alpha). (wikipedia.org)
  • iii) screen hIDO1 (human indoleamine 2,3-dioxygenase) inhibitors and evaluate their effect on downstream TRP-catabolizing enzymes. (bvsalud.org)
  • encoded by Slc39a1), a mediator of citrate efflux from the tricarboxylic acid cycle, SLC13A5 mediates citrate entry from blood and its activity exerts homeostatic control of cytoplasmic citrate. (biomed.news)