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Pathway Description
Metabolism and Physiological Effects of Indoxyl glucuronide
Homo sapiens
Metabolic Pathway
Created: 2021-03-18
Last Updated: 2023-10-25
Indoxyl glucuronide is an indole compound that is formed through gut microbial metabolism from dietary tryptophan and a glucuronidation 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 it undergoes a reaction in a liver hepatocyte through a glucuronosyltransferase enzyme to form Indoxyl glucuronide. When this compound returns back into systemic circulation it is shown to be a major uremic toxin through high levels of retention. Indoxyl glucuronide is shown to cause a reduction in Erythropoetin production which ultimately results in renal anemia.
References
Metabolism and Physiological Effects of Indoxyl glucuronide References
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.
Meyer, T. W., & Hostetter, T. H. (2012). Uremic solutes from colon microbes. Kidney international, 81(10), 949-954.
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
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.
Deeley MC, Yanofsky C: Nucleotide sequence of the structural gene for tryptophanase of Escherichia coli K-12. J Bacteriol. 1981 Sep;147(3):787-96.
Pubmed: 6268608
Tokushige M, Tsujimoto N, Oda T, Honda T, Yumoto N, Ito S, Yamamoto M, Kim EH, Hiragi Y: Role of cysteine residues in tryptophanase for monovalent cation-induced activation. Biochimie. 1989 Jun;71(6):711-20. doi: 10.1016/0300-9084(89)90087-4.
Pubmed: 2502187
Burland V, Plunkett G 3rd, Daniels DL, Blattner FR: DNA sequence and analysis of 136 kilobases of the Escherichia coli genome: organizational symmetry around the origin of replication. Genomics. 1993 Jun;16(3):551-61. doi: 10.1006/geno.1993.1230.
Pubmed: 7686882
Sarsero JP, Wookey PJ, Gollnick P, Yanofsky C, Pittard AJ: A new family of integral membrane proteins involved in transport of aromatic amino acids in Escherichia coli. J Bacteriol. 1991 May;173(10):3231-4. doi: 10.1128/jb.173.10.3231-3234.1991.
Pubmed: 2022620
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
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