Computer Simulation of Enzyme Deficiency in Human Erythrocyte Using the E-Cell System

We previously reported a computer model of the human erythrocyte using E-CELL simulation system [1, 2]. The model has three major metabolic pathways, including glycolysis, the pentose phosphate pathway, and nucleotide metabolism, as well as Na+/K+ pumps, some transport systems, and magnesium complexation. All kinetic parameters for enzymes were based on the experimental data published in the literature. The model has reached the steady state, which indicates that it is very closed to approximating the real erythrocyte. In this work, we carried out the simulation of enzyme deficiencies such as that of Glucose-6phosphate dehydrogenase (G6PD). G6PD is a key enzyme that produces NADPH in the Pentose Phosphate Pathway. NADPH is required for the reduction of glutathione disulfide (GSSG) by glutathione reductase. A major function of glutathione (GSH) in the erythrocyte is to eliminate H2O2 and organic hydroperoxides. Peroxides are eliminated through the action of glutathione peroxidase, yielding GSSG.