Quinolinic Acid and Active Oxygens
Quinolinic acid (QA, pyridine-2,3-dicarboxylic acid) is an intermediate of the kynurenine pathway in the tryptophan metabolism, which has been detected in the central nervous system (Gal and Sherman, 1978; Speciale and Schwarcz, 1993), and behaves as an excitotoxin (Lapin, 1978; Schwarcz et al., 1983). Recently, it has been proposed that QA and other metabolites of tryptophan may be involved in the brain pathology accompanying neuroinflammatory conditions, and also implicated in the pathophysiology of brain ischemia (Jhamandas and Boegman, 1994). The neuroexcitatory and neurotoxic actions have been suggested to be mediated by NMDA receptor (recently, its subtypes) (Schwarcz et al., 1984; Nakanishi, 1992),. However, the proximate cause of cell death at metabolic level has remained elusive. In the brain, there are numerous sources of oxygen-derived free radicals and they may exert a large variety of effects upon importnat central nervous system functions. Several studies have pointed to the role of metal ions, especially iron, in forming oxygen-derived free radicals (Barber, 1966; Vladimirov et al., 1980), which introduce several reactions such as lipid peroxidation, DNA chain breakage and others in the brain. The purpose of this experiment was to see the interaction of QA with iron ion (complex formation), the electron transfer to oxygen molecules from the complex (superoxide formation) and superoxide-mediated reactions such as lipid peroxidation and DNA chain breakage in vitro. Also, tryptophan metabolites which are known to be antagonist for QA were examined in the QA-iron system.
KeywordsLipid Peroxidation Active Oxygen Quinolinic Acid Kynurenic Acid Kynurenine Pathway
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