PathWhiz

Pathway Description

Metabolism and Physiological Effects of Para-cresyl sulphate

Homo sapiens

Metabolic Pathway

Para-cresyl sulphate(P-cresyl sulphate) is a phenolic compound that is formed through gut microbial metabolism from dietary tyrosine and a sulfation 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. P-cresol then ultimately undergoes a sulfation reaction in a liver hepatocyte through a sulfotransferase enzyme to form P-cresyl sulphate. When P-cresyl sulphate returns back into systemic circulation it is shown to be a major uremic toxin through high levels of retention. P-cresyl sulphate is shown to cause carotid atherosclerosis and enhance reactive oxygen species production causing cardiac toxicity and leads to cardiomyocyte apoptosis.

References

Metabolism and Physiological Effects of Para-cresyl sulphate References

Meyer, T. W., & Hostetter, T. H. (2012). Uremic solutes from colon microbes. Kidney international, 81(10), 949-954.

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.

Steglich, M., Hofmann, J. D., Helmecke, J., Sikorski, J., Spröer, C., Riedel, T., ... & Nübel, U. (2018). Convergent loss of ABC transporter genes from Clostridioides difficile genomes is associated with impaired tyrosine uptake and p-cresol production. Frontiers in microbiology, 9, 901.

Pubmed: 28146081

Pubmed: 20216

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.

Mutsaers, H. A., Caetano-Pinto, P., Seegers, A. E., Dankers, A. C., van den Broek, P. H., Wetzels, J. F., ... & Masereeuw, R. (2015). Proximal tubular efflux transporters involved in renal excretion of p-cresyl sulfate and p-cresyl glucuronide: Implications for chronic kidney disease pathophysiology. Toxicology in Vitro, 29(7), 1868-1877.

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		4-Hydroxyphenylpyruvic acid
		Carbon dioxide
		L-Glutamic acid
		L-Tyrosine
		Oxoglutaric acid
		Oxygen
		p-Cresol
		p-Cresol sulfate
		p-Hydroxyphenylacetic acid
		Pyridoxal 5'-phosphate

Visualize Protein Data

		4-hydroxyphenylacetate decarboxylase glycyl radical subunit
		ABC transporter, substrate-binding lipoprotein
		Broad substrate specificity ATP-binding cassette transporter ABCG2
		Sulfotransferase 1A3/1A4
		Tyrosine aminotransferase
		Unknown

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