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Pathway Description
Metabolism and Physiological Effects of Indoxyl Sulfate
Homo sapiens
Metabolic Pathway
Created: 2021-03-18
Last Updated: 2023-09-01
Indoxyl sulfate is an indole compound that is formed through gut microbial metabolism from dietary tryptophan and a sulfation reaction in liver hepatic cells. After being transported into gut microbes, tryptophan undergoes a reaction with the enzyme tryptophanase to form indole. Indole that is produced from the gut microbes then enters systemic circulation. Ultimately this compound undergoes a sulfation reaction in a liver hepatocyte through a sulfotransferase enzyme to form Indoxyl sulfate. When this compound returns back into systemic circulation it is shown to be a major uremic toxin through high levels of retention. Indoxyl sulfate, like indoxyl glucuronide, is shown to cause a reduction in Erythropoetin production which ultimately results in renal anemia. It is also shown to cause vascular calcification and disrupt the electron transport chain and oxidative phosphorylation causing muscle atrophy
References
Metabolism and Physiological Effects of Indoxyl Sulfate References
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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.
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