Quinolinic acid

Quinolinic acid (abbreviated QUIN or QA), also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. It is a colorless solid. It is the biosynthetic precursor to niacin. Quinolinic acid is a downstream product of the kynurenine pathway, which metabolizes the amino acid tryptophan. It acts as an NMDA receptor agonist. Quinolinic acid has a potent neurotoxic effect. Studies have demonstrated that quinolinic acid may be involved in many psychiatric disorders, neurodegenerative processes in the brain, as well as other disorders. Within the brain, quinolinic acid is only produced by activated microglia and macrophages. In 1949 L. Henderson was one of the earliest to describe quinolinic acid. Lapin followed up this research by demonstrating that quinolinic acid could induce convulsions when injected into mice brain ventricles. However, it was not until 1981 that Stone and Perkins showed that quinolinic acid activates the N-methyl--aspartate receptor (NMDAR). After this, Schwarcz demonstrated that elevated quinolinic acid levels could lead to axonal neurodegeneration. 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. This compound is commercially available. It is generally obtained by the oxidation of quinoline. Oxidants such as ozone, hydrogen peroxide, and potassium permanganate have been used. Electrolysis is able to perform the transformation as well. 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. Condensation of iminosuccinate with glyceraldehyde-3-phosphate, mediated by quinolinate synthase, affords quinolinic acid. Quinolinic acid is a byproduct of the kynurenine pathway, which is responsible for catabolism of tryptophan in mammals.