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Pathway Description
Kynurenine
Homo sapiens
Metabolic Pathway
Kynurenine 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 reaction with the enzyme tryptophan-2,3-dioxygenase to form kynurenine. 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. Kynurenine is shown to activate aryl hydrocarbon receptors that can lead to renal impairment, and it also disrupts the electron transport chain and oxidative phosphorylation causing muscle atrophy.
References
Kynurenine References
Meyer, T. W., & Hostetter, T. H. (2012). Uremic solutes from colon microbes. Kidney international, 81(10), 949-954.
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.
Graboski, A. L., & Redinbo, M. R. (2020). Gut-derived protein-bound uremic toxins. Toxins, 12(9), 590.
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.
Hubbard TD, Murray IA, Perdew GH: Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation. Drug Metab Dispos. 2015 Oct;43(10):1522-35. doi: 10.1124/dmd.115.064246. Epub 2015 Jun 3.
Pubmed: 26041783
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