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OBJECTIVES: To develop a compartmental model which describes vitamin B-6 metabolism in the blood and tissues of the mouse under a variety of circumstances and to develop a computer application which can utilize the data to display the movement of tracer through the various compartments. METHODS: A circulation model was developed. Literature data from vitamin B-6 feeding studies and tracer experiments were used to develop an appropriate compartmental model using the SAAM II program (The Epsilon Group, Charlottesville, VA). A web-based application transforms the mass and flux data into intuitive and interactive graphical illustrations. RESULTS: Describing the interconversions between pyridoxine, pyridoxine 5’-phosphate, pyridoxal, pyridoxal 5’-phosphate, pyridoxamine, pyridoxamine 5’-phosphate and 4-pyridoxic acid in multiple tissues required 231 compartments. The largest amount of data deals with liver and brain. The model includes less detailed information on plasma, erythrocytes, gut, bone, muscle, heart, kidney, skin, adipose tissue and lung. The model includes adjustments to food intake, water intake, cardiac output, binding sites and Vmax values for enzymes based on the specified body weight of experimental animals. We did not include growth curves at this time. The model uses two parallel systems to monitor the steady state of endogenous metabolites as well as following tracer administration. Binding mechanisms are included to provide conservation of vitamin B-6 when intake is reduced. The model provides reasonable agreement with literature data on various vitamin B-6 intakes as well as oral and intravenous administration of tracer. It also reveals some areas which need clarification. For example, we have not found any detailed analysis of vitamin B-6 metabolites in mouse urine. There is little pyridoxic acid in plasma or urine suggesting that pyridoxic acid may not be the primary end product for vitamin B-6 in the mouse. The visualization application shows changes in the content of all 231 compartments over time illustrating the value of such computer applications in the interpretation of large, complex models. CONCLUSIONS: This model facilitates the simulation of various dietary and physiological conditions on vitamin B-6 metabolism in mice. We hope to adapt it to rats, pigs and humans. FUNDING SOURCES: Purdue University Fort Wayne. |
