IN SILICO MODELING OF THE REDOX METABOLISM IN HUMAN ERYTHROCYTES
Abstract
There was elaborated the mathematical model of erythrocytes metabolism, including glycolysis (Embden-Meyerhof pathway), pentose phosphate pathway, metHb restoration pathway, Н2О2 metabolism reaction. The final model includes 50 reactions and 60 metabolites. Within the model was studied the change of activity of some enzymes and concentrations of metabolites in stationary state, that take part in the processes of utilization of oxygen active forms and restoration of metgemoglobin, depending on amount of exogenous and endogenous Н2О2. There was demonstrated the threshold character of changes of the many studied parameters, that testifies that the cells can be practically in physiological state at the change of external conditions for rather long time.
There was carried out an assessment of redox-state of erythrocytes at oxidizing load: was demonstrated the change of EGSSG/2GSH, ENADP+/NADPH and ENAD+/NADH from the concentration of endogenous Н2О2. There was established that in the studied diapason of concentrations of endogenous Н2О2 was observed the high slope of the change of EGSSG/2GSH, that was not observed for ENADP+/NADPH and the other redox-pairs.
The results of modeling coincide with existing views on the functioning of enzymes of antioxidant protection in human erythrocytes and testify to the possibility of practical use of the model
Keywords
References
Rifkind, J. M., Nagababu, E. (2013). Hemoglobin Redox Reactions and Red Blood Cell Aging. Antioxidants & Redox Signaling, 18 (17), 2274–2283. doi: 10.1089/ars.2012.4867
Martinovich, G. G., Martinovich, I. V., Cherenkevich, S. N., Sauer, H. (2010). Redox Buffer Capacity of the Cell: Theoretical and Experimental Approach. Cell Biochemistry and Biophysics, 58 (2), 75–83. doi: 10.1007/s12013-010-9090-3
Holzhütter, H.-G. (2004). The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks. European Journal of Biochemistry, 271 (14), 2905–2922. doi: 10.1111/j.1432-1033.2004.04213.x
Bulik, S., Grimbs, S., Huthmacher, C., Selbig, J., Holzhütter, H. G. (2008). Kinetic hybrid models composed of mechanistic and simplified enzymatic rate laws - a promising method for speeding up the kinetic modelling of complex metabolic networks. FEBS Journal, 276 (2), 410–424. doi: 10.1111/j.1742-4658.2008.06784.x
Schuster, S., Klamt, S., Weckwerth, W., Moldenhauer, F., Pfeiffer, T. (2002). Use of network analysis of metabolic systems in bioengineering. Bioprocess and Biosystems Engineering, 24 (6), 363–372. doi: 10.1007/s004490100253
Yachie-Kinoshita, A., Nishino, T., Shimo, H., Suematsu, M., Tomita, M. (2010). A Metabolic Model of Human Erythrocytes: Practical Application of the E-Cell Simulation Environment. Journal of Biomedicine and Biotechnology, 2010, 1–14. doi: 10.1155/2010/642420
Shimo, H., Nishino, T., Tomita, M. (2011). Predicting the Kinetic Properties Associated with Redox Imbalance after Oxidative Crisis in G6PD-Deficient Erythrocytes: A Simulation Study. Advances in Hematology, 2011, 1–10. doi: 10.1155/2011/398945
Salvador, A., Savageau, M. A. (2003). Quantitative evolutionary design of glucose 6-phosphate dehydrogenase expression in human erythrocytes. Proceedings of the National Academy of Sciences, 100 (24), 14463–14468. doi: 10.1073/pnas.2335687100
Kinoshita, A., Nakayama, Y., Kitayama, T., Tomita, M. (2007). Simulation study of methemoglobin reduction in erythrocytes. FEBS Journal, 274 (6), 1449–1458. doi: 10.1111/j.1742-4658.2007.05685.x
Shimo, H., Arjunan, S. N. V., Machiyama, H., Nishino, T., Suematsu, M., Fujita, H. et. al (2015). Particle Simulation of Oxidation Induced Band 3 Clustering in Human Erythrocytes. PLOS Computational Biology, 11 (6), e1004210. doi: 10.1371/journal.pcbi.1004210
Mulquiney, P. J., Kuchel, P. W. (1999). Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations1: equations and parameter refinement. Biochemical Journal, 342 (3), 581–596. doi: 10.1042/bj3420581
Dash, R. K., Korman, B., Bassingthwaighte, J. B. (2015). Simple accurate mathematical models of blood HbO2 and HbCO2 dissociation curves at varied physiological conditions: evaluation and comparison with other models. European Journal of Applied Physiology, 116 (1), 97–113. doi: 10.1007/s00421-015-3228-3
Low, F. M., Hampton, M. B., Peskin, A. V., Winterbourn, C. C. (2007). Peroxiredoxin 2 functions as a noncatalytic scavenger of low-level hydrogen peroxide in the erythrocyte. Blood, 109 (6), 2611–2617. doi: 10.1182/blood-2006-09-048728
Johnson, R., Goyettejr, G., Ravindranath, Y., Ho, Y. (2005). Hemoglobin autoxidation and regulation of endogenous H2O2 levels in erythrocytes. Free Radical Biology and Medicine, 39 (11), 1407–1417. doi: 10.1016/j.freeradbiomed.2005.07.002
Scarpa, M., Momo, F., Viglino, P., Vianello, F., Rigo, A. (1996). Activated oxygen species in the oxidation of glutathione A kinetic study. Biophysical Chemistry, 60 (1-2), 53–61. doi: 10.1016/0301-4622(96)00002-6
Tao, Z., Raffel, R. A., Souid, A.-K., Goodisman, J. (2009). Kinetic Studies on Enzyme-Catalyzed Reactions: Oxidation of Glucose, Decomposition of Hydrogen Peroxide and Their Combination. Biophysical Journal, 96 (7), 2977–2988. doi: 10.1016/j.bpj.2008.11.071
Ng, C. F., Schafer, F. Q., Buettner, G. R., Rodgers, V. G. J. (2007). The rate of cellular hydrogen peroxide removal shows dependency on GSH: Mathematical insight into in vivo H2O2 and GPx concentrations. Free Radical Research, 41 (11), 1201–1211. doi: 10.1080/10715760701625075
Mendes, P., Hoops, S., Sahle, S., Gauges, R., Dada, J., Kummer, U. (2009). Computational Modeling of Biochemical Networks Using COPASI. Systems Biology, 17–59. doi: 10.1007/978-1-59745-525-1_2
Biswas, S., Chida, A. S., Rahman, I. (2006). Redox modifications of protein–thiols: Emerging roles in cell signaling. Biochemical Pharmacology, 71 (5), 551–564. doi: 10.1016/j.bcp.2005.10.044
Jones, D. P. (2002). [11] Redox potential of GSH/GSSG couple: Assay and biological significance. Methods in Enzymology, 93–112. doi: 10.1016/s0076-6879(02)48630-2
DOI: http://dx.doi.org/10.21303/2504-5695.2016.00053
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