Mathematical model gives insights into vitamin B6 and kynurenine metabolism

Abstract

Vitamin B6 deficiency and oral contraceptive (OC) use have been associated with impaired tryptophan (trp) metabolism. To investigate the underlying mechanism, we developed a mathematical model of trp metabolism via the kynurenine pathway. The model includes kinetics from gut to liver, muscle and brain as well as trp concentrations in portal and peripheral circulation. Regulatory mechanisms and inhibition of relevant enzymes were included. Changes in urinary excretion of trp catabolites were observed as a function of vitamin B6 status using our model. Excretions of kynurenine, 3‐hydroxykynurenine and xanthurenic acid were increased in vitamin B6 deficiency as reported in the literature. Predicted effects of a trp load alone or concurrent with vitamin B6 deficiency also were consistent with experimental data. Dynamic variations of trp and trp metabolites were observed after simulation of trp input due to meals. Changes in trp metabolites concentrations were seen after induction of tryptophan 2,3‐dioxygenase alone or in combination with impaired B6 status as reported in OC users. Our findings support the use of this mathematical model as a tool to test trp metabolism in different conditions to complement, clarify and provide new insights into the associations of altered trp metabolism with OC use and vitamin B6 deficiency. Supported by NIH grant DK072398, and NSF grants DMS‐061670 (MR, HFN), EF‐1038593 (HFN. MR).