PathWhiz

Pathway Description

Metabolism and Physiological Effects of Kynurenic Acid

Homo sapiens

Metabolic Pathway

Kynurenic 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 tryptophan undergoes a reaction with the enzyme tryptophan-2,3-dioxygenase to initially form kynurenine and then with a kynurenine aminotransferase enzyme to ultimately form kynurenic acid. When this compound enters into systemic circulation it is shown to be a major uremic toxin through high levels of retention. Kynurenic acid 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

Metabolism and Physiological Effects of Kynurenic Acid 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

Highlighted elements will appear in red.

Highlight Compounds

	Heme
	Kynurenic acid
	L-Kynurenine
	L-Tryptophan
	Pyridoxal 5'-phosphate

Highlight Proteins

	Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial
	Tryptophan 2,3-dioxygenase
	Unknown

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