Fig. 1

Metabolic pathway of tyrosine into p-cresyl sulfate (PCS). l-tyrosine can be reversibly converted to 4-hydroxyphenylpyruvate by tyrosine transaminase, aromatic-amino-acid transaminase or phenylalanine dehydrogenase. 4-Hydroxyphenylpyruvate is the precursor of 4-hydroxyphenylacetate, which is catalyzed by p-hydroxyphenylpyruvate oxidase, and can subsequently be decarboxylated to p-cresol by p-hydroxyphenylacetate decarboxylase. The majority of p-cresol is sulfated into the PCS by aryl sulfotransferases, and a small fraction is metabolized to p-cresyl glucuronide by UDP-glucuronyltransferases. The processes marked by the yellow box occur in the gut microbiota, and the processes marked by the blue box occur in the gut mucosa and liver of the host