KINETIC MODELLING OF SULFATE ION TRANSPORT THROUGH BAND 3 PROTEIN OF ERYTHROCYTES
DOI: http://dx.doi.org/10.30970/sbi.1904.856
Abstract
Background. Assessment of the kinetic properties of ion transport involving band 3 protein (B3p, AE1) is a sensitive tool for monitoring functional changes in erythrocytes under the influence of external factors. The aim of the work was to study the rate of H+,SO42-/Cl exchange in erythrocytes under osmotic and metabolic stress. To achieve this goal, a mathematical model was developed that uses parameter identification methods based on the results of experimental studies.
Materials and Methods. Erythrocytes were incubated in a medium of Na-phosphate buffer (0.015 M, pH 7.4) containing 0.15 M NaCl without glucose. During 3 hours of incubation, the ability of cells to anion exchange, the amount of uptake of SO42-, the level of oxidation of sulfhydryl groups and the content of ligand forms of hemoglobin (Hb) in the membrane-bound fraction were tested. To assess anion exchange, a mathematical model was created that involves the search for kinetic parameters using search optimization methods.
Results. The results obtained indicate that under the influence of osmotic and metabolic stress and hypoxia, the work of the anion exchanger AE1 slows down, which is reflected in a decrease in the exchange rate constant HCO3/Cl, Vmax, H+,SO42-/Clexchange. The predicted decrease in the content of SO42--ions in cells is has been confirmed by experimental data. According to the modelling results, incubation of cells leads to activation of the Na+,K+,2Cl cotransporter and Na+/H+ exchanger, and inhibition of the flux through the K+,2Cl cotransporter. Assessment of the composition of membrane-bound hemoglobin indicates that the decrease in the speed of AE1 is due to the formation of the deoxyHb-B3p complex and oxidative processes in cells.
Conclusion. The results of mathematical modelling and experimental data indicate the existence of universal O2-dependent mechanisms of regulation of molecular processes in erythrocytes that are based on competition between deoxyHb and other proteins for binding sites with band 3 protein.
Keywords
sulfate uptake, anion transport, AE1, chloride-bicarbonate antiporters, anion exchange, membrane-bound hemoglobin, ligand forms of hemoglobin, hemichrome, ferrylhemoglobin
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