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Pathway Description
Metabolism and Physiological Effects of Para-cresyl glucuronide
Homo sapiens
Metabolic Pathway
Created: 2021-04-12
Last Updated: 2023-10-25
Para-cresyl glucuronide (P-cresyl glucuronide) is a phenolic compound that is formed through gut microbial metabolism from dietary tyrosine and a glucuronidation reaction in liver hepatic cells. After being transported into gut microbes, tyrosine undergoes reactions with the enzymes tyrosine transaminase, 4-hydroxyphenylpyruvate oxidase and 4-hydroxylphenylacetate decarboxylase to form para-cresol. Most of the p-cresol that is produced from the gut microbes then enters systemic circulation and is converted into P-cresyl sulphate by the liver. However a small portion also gets converted to P-cresyl glucuronide. This occurs when P-cresol then undergoes a reaction in a liver hepatocyte through a glucuronosyltransferase enzyme to form P-cresyl glucuronide. When P-cresyl glucuronide returns back into systemic circulation it is shown to be a uremic toxin with some similar effects to P-cresyl sulphate. P-cresyl glucuronide is shown to induce stress in renal tubule cells as well as the effect shared by p-cresyl sulphate in causing enhanced oxidative stress.
References
Metabolism and Physiological Effects of Para-cresyl glucuronide References
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Passmore, I. J., Letertre, M. P., Preston, M. D., Bianconi, I., Harrison, M. A., Nasher, F., ... & Dawson, L. F. (2018). Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria. PLoS pathogens, 14(9), e1007191.
Selmer, T., & Andrei, P. I. (2001). p‐Hydroxyphenylacetate decarboxylase from Clostridium difficile: A novel glycyl radical enzyme catalysing the formation of p‐cresol. European Journal of Biochemistry, 268(5), 1363-1372.
Dawson, L. F., Donahue, E. H., Cartman, S. T., Barton, R. H., Bundy, J., McNerney, R., ... & Wren, B. W. (2011). The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains. BMC microbiology, 11(1), 1-10.
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Guillemette C, Ritter JK, Auyeung DJ, Kessler FK, Housman DE: Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene. Pharmacogenetics. 2000 Oct;10(7):629-44.
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