Interrelations between Iron and Vitamin A-Studied Using Systems Approach

Int J Mol Sci. 2022 Jan 21;23(3):1189. doi: 10.3390/ijms23031189.

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.

Keywords: iron deficiency; iron homeostasis; modeling; petri nets; t-invariants; vitamin a deficiency.

MeSH terms

  • Algorithms*
  • Anemia, Iron-Deficiency / complications
  • Anemia, Iron-Deficiency / metabolism*
  • Anemia, Iron-Deficiency / pathology
  • Computer Simulation
  • Hepcidins / metabolism*
  • Humans
  • Iron / metabolism*
  • Models, Theoretical
  • Systems Analysis*
  • Vitamin A / metabolism*
  • Vitamin A Deficiency / complications
  • Vitamin A Deficiency / metabolism*
  • Vitamin A Deficiency / pathology

Substances

  • Hepcidins
  • Vitamin A
  • Iron