Developing a compartmental model of human vitamin B-6 metabolism which accommodates changes

Abstract

Our goal has been to develop a compartmental model of vitamin B-6 metabolism which can respond appropriately to a variety of conditions using data from the literature. Modeling vitamin B-6 metabolism is challenging because vitamin B-6 is interconverted between 7 common forms: pyridoxine, pyridoxine 5\u27-phosphate, pyridoxal, pyridoxal 5\u27-phosphate, pyridoxamine, pyridoxamine 5\u27-phosphate and 4-pyridoxic acid. In addition, in humans 5-pyridoxic acid becomes a significant metabolite with high vitamin B-6 intakes. Development of the model utilized the Simulation, Analysis and Modeling (SAAM) software originally developed at NIH and now available as WinSAAM(http://www.winsaam.org/) and SAAM II (https://tegvirginia.com/solutions/saam-ii/). The model is designed to achieve a steady state before changes are introduced. We found that several characteristics were required in the model. Because plasma values fluctuate with meal intake, the model needed to reflect meal intake. Because experimental data reveals flushing effects, at least some pool sizes must have limits to generate flushing. Because reducing intake has limited effect on the vitamin B-6 content of muscle, which accounts for about 70% of the body pool, there must be a mechanism to conserve vitamin B-6. Models provide a method of simulating various situations. In the case of vitamin B-6 this model can be used to estimate turnover rates, the effect of changes in intake on body pools, and the role of erythrocytes in vitamin B-6 metabolism. The model can also be used to determine optimal sampling times for proposed experiments. It can easily be updated as new data become available. We are still working to improve the fit of the model to various data sets. We also hope to add more data on circulation and additional tissues