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Pathway Description
Metabolism and Physiological Effects of Quinolinic Acid
Homo sapiens
Metabolic Pathway
Quinolinic acid is an indole uremic toxin compound that is formed through metabolism from dietary tryptophan in liver hepatic cells. After being transported into a hepatocyte from portal circulation the amino acid tryptophan undergoes a multi-step reaction with the enzymes tryptophan-2,3-dioxygenase, kynurenine 3-monooxygenase, kynureninase, and 3-hydroxyanthranilate 3,4-dioxygenase to form quinolinic acid. When this compound enters into systemic circulation it is shown to be a major uremic toxin when high levels of it are retained in the blood and not excreted in urine. Quinolinic acid is shown to have major neurotoxic effects on the brain by acting as an NMDA receptor agonist, causing excessive glutamate release and lipid peroxidation.
References
Metabolism and Physiological Effects of Quinolinic Acid References
Graboski, A. L., & Redinbo, M. R. (2020). Gut-derived protein-bound uremic toxins. Toxins, 12(9), 590.
Van der Leek, A. P., Yanishevsky, Y., & Kozyrskyj, A. L. (2017). The kynurenine pathway as a novel link between allergy and the gut microbiome. Frontiers in immunology, 8, 1374.
Lim, Y. J., Sidor, N. A., Tonial, N. C., Che, A., & Urquhart, B. L. (2021). Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins, 13(2), 142.
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