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Pathway Description
Metabolism and Physiological Effects of Indole Acetic Acid
Homo sapiens
Metabolic Pathway
Indole acetic acid is an indole compound that is formed through gut microbial metabolism from dietary tryptophan through the indole-3-acetamide pathway . After being transported into gut microbes, tryptophan undergoes a reaction with the enzymes tryptophan monooxygenase and indole-3-acetamide hydrolase to form indole acetic acid. Indole acetic acid that is produced from the gut microbes then enters systemic circulation. This compound is shown to be a uremic toxin through high levels of retention. Indole acetic acid is shown to cause inflammation and disrupt the electron transport chain and oxidative phosphorylation causing muscle atrophy.
References
Metabolism and Physiological Effects of Indole Acetic Acid References
Gryp, T., De Paepe, K., Vanholder, R., Kerckhof, F. M., Van Biesen, W., Van de Wiele, T., ... & Glorieux, G. (2020). Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease. Kidney international, 97(6), 1230-1242.
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., ... & Romani, L. (2013). Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity, 39(2), 372-385.
Tsavkelova, E., Oeser, B., Oren-Young, L., Israeli, M., Sasson, Y., Tudzynski, B., & Sharon, A. (2012). Identification and functional characterization of indole-3-acetamide-mediated IAA biosynthesis in plant-associated Fusarium species. Fungal Genetics and Biology, 49(1), 48-57.
Asai, H., Hirata, J., & Watanabe-Akanuma, M. (2018). Indoxyl glucuronide, a protein-bound uremic toxin, inhibits hypoxia-inducible factor‒dependent erythropoietin expression through activation of aryl hydrocarbon receptor. Biochemical and biophysical research communications, 504(2), 538-544.
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.
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