Fig. 4: Metabolic pathways of tryptophan in key organs.

A Following a diet enriched with tryptophan, there is an expected increase in circulating tryptophan levels. Most of the diet-derived tryptophan in circulation is shunted into the kynurenine pathway in the liver, where it ultimately contributes to de novo NAD+ synthesis. Intermediate metabolites of the kynurenine pathway, such as kynurenine and quinolinate, are released back into circulation. The end-products of the kynurenine pathway, including 1-methylnicotinamide (1-MN) and N-methyl-2-pyridone-5-carboxamide (2-PY), along with tryptophan, kynurenine, and quinolinate, are excreted in the urine. Some of the circulating tryptophan is taken up by the brain and utilized for serotonin synthesis via the enzyme tryptophan hydroxylase. Additionally, intestinal enterochromaffin cells also use tryptophan to produce serotonin, which significantly contributes to circulating serotonin levels. In the gut, indole-producing bacteria convert tryptophan into indole, which, upon absorption, is metabolized in the liver into 3-indoxyl sulfate (3-IS), with the majority subsequently excreted in the urine. B Correlation of tryptophan metabolites across various biofluids and tissue compartments illustrates the interconnected pathway of tryptophan metabolites within the body. Spearman correlation coefficient (ρ) was used to evaluate the strength of this relationship. Data from all three groups were used for the analysis. Multiple hypothesis testing was not adjusted. Only significant pairs are displayed. ***unadjusted p < 0.001, **unadjusted p < 0.01, *unadjusted p < 0.05.