Abstract
A deficiency of vitamin A (VAD) and iron is the most common nutritional problem affecting people worldwide. Given the scale of the problem, the interactions between vitamin A and iron levels are widely studied. However, the exact mechanism of the impact of vitamin A on the regulation of iron metabolism remains unclear. An extremely significant issue becomes a better understanding of the nature of the studied biological phenomenon, which is possible by using a systems approach through developing and analyzing a mathematical model based on a Petri net. To study the considered system, the t-cluster analysis, the significance analysis, and the analysis of the average number of transition firings were performed. The used analyses have allowed distinguishing the most important mechanisms (both subprocesses and elementary processes) positively and negatively regulating an expression of hepcidin and allowed to distinguish elementary processes with a higher frequency of occurrence compared to others. The analysis also allowed to resolve doubts about the discrepancy in literature reports, where VAD leads to positive regulation of hepcidin expression or to negative regulation of hepcidin expression. The more detailed analyses have shown that VAD more frequently positively stimulates hepcidin expression and this mechanism is more significant than the mechanism inhibiting hepcidin expression indirectly by VAD.
Highlights
Using a systems approach based on Petri nets allows the analysis of biological phenomena as systems characterized by a complex net of interactions
In the case of the studied system focusing on the effect of vitamin A deficiency on the regulation of iron homeostasis, a thorough understanding of the biological problem is difficult due to contradictory literature information
The final analysis allows resolving some doubts as to the discrepancy in literature reports, where vitamin A deficiency (VAD) leads to negative regulation of hepcidin expression [2] or to positive regulation of hepcidin expression [1]
Summary
The first literature reports on the relationship between vitamin A deficiency and low iron levels come from studies conducted in the 1920s [7,8,9]. The study of these relationships raises a lot of controversy among researchers, which can be observed by the discrepancies in the literature reports. With the purpose to understand the rules underlying this phenomenon, a systems approach based on Petri nets [10,11,12] was used and described in this paper This approach allows the systematization of knowledge and a better understanding of the nature of the biological system through creating a mathematical model being a representation of the complex network of interactions [13]
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