Simulation of Human Erythrocyte Metabolism

Abstract

Since a mature mammalian erythrocyte is enucleated and it is void of mitochondria, gene expression does not take place, while glycolysis is the only mechanism to produce ATP. This simplicity makes its metabolism unique from other cells. Due to its simple structure and the traceability of the cell, erythrocyte metabolism and enzymology have been well studied over the last three to four decades. Although vast amounts of erythrocyte component information is available, the quantitative and physiological role of the metabolism is still an open question because the nature of the cellular function is the complex dynamics of components. Mathematical models for biochemical pathways comprising complex networks are of particular interest in order to identify the features of biological systems that cannot be investigated by the analysis of their individual components alone. Because of its simplicity, the robustness of the erythrocyte that enables the cell to circulate in the body for about 120 days and the abundance of knowledge, erythrocytes have been a good subject for numerous modeling and simulation studies. There is a long history of detailed metabolic models of erythrocyte metabolism with differential equations. The first mathematical models of erythrocyte metabolism were developed by Rapoport et al and the model by Heinrich et al, which only included the glycolytic pathway.1–3 Ataullakhanov et al expanded the glycolytic model to represent the pentose phosphate pathway.4 Subsequently, adenine nucleotide metabolism was first considered by Schauer et al.5 The comprehensive biochemical network, which has been widely accepted as the complete network of the metabolic system in erythrocytes, was reconstructed by Joshi and Palsson in 1989–1990, involving membrane transports, the Na⁺/K⁺ pump and osmotic pressure.6–9