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. 2022 Mar 17;14(3):221. doi: 10.3390/toxins14030221

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Global metabolic pathways of tryptophan according to the most recent insights. Different enzymes are involved in the generation of uremic toxins and activators of aryl hydrocarbon receptor (AhR). (1) Tryptophanase; (2) indoleamine-2,3-dioxygenases (IDOs) and tryptophan-2,3-dioxgenase (TDO) and (3) the newly identified interleukin 4-induced-1 (IL4I1). Indole is further metabolized in the liver (green arrows) by cytochrome P450 family 2 subfamily E member 1 (CYP2E1), resulting in indoxyl and indoxyl sulfate (sulfotransferase) and indole-3-acetic acid (acetate transferase). Both the IDOs/TDO (red arrows) and IL4I1-dependent pathways (purple arrows) are involved in the generation of kynurenic acid. The end-metabolites are excreted by the kidneys (yellow arrows). For the sake of completeness, in grey, (4) the serotonin pathway.