Computational modeling of Quiescent Platelet Energy Metabolism in the Context of Whole-body Glucose Turnover
Mathematical modelling of natural phenomena, Tome 11 (2016) no. 6, pp. 91-101.

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Platelets are anucleate blood cells circulating in the bloodstream for up to 9 days in quiescent state. Upon vessel wall injury, platelets become activated, change their shape and adhere to the vessel wall and each other, thus forming a thrombus and preventing the blood loss. To get energy for these processes, they can use oxidative phosphorylation and glycolysis utilizing blood glucose, stored glycogen or fatty acids as fuel. Yet, there is no agreement in experimental data on platelet functioning in quiescent and activated states. This study is a systematic analysis of the energy abilities of quiescent platelets through mathematical modeling of their energy metabolism by Flux Balance Analysis (FBA). As a result of the FBA analysis we concluded that a platelet even in quiescent state utilizes blood glucose at high rate (0.1 mM/s), producing lactate from 99% of it and about 0.2 mM/s ATP from glycolysis and respiration. Such high fluxes of glucose are not always available due to platelet’s glucose transporter (GLUT3)kinetic limitations. We positioned a “FBA” platelet in human glucose/insulin/glucagon PBPK/PD model to theoretically investigate platelet metabolism in close-to-real conditions. The main result of our study is that the stored glycogen could be daily used and resynthesized during platelet lifetime.
DOI : 10.1051/mmnp/201611606

T.O. Shepelyuk 1, 2, 3 ; M.A. Panteleev 1, 2, 4, 5 ; A.N. Sveshnikova 1, 2, 4, 6

1 Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences 4 Kosygina St, Moscow, Russia, 119991
2 Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology 1 Samory Mashela St, Moscow, Russia, 117198
3 Faculty of Medicine, Lomonosov Moscow State University Lomonosovsky pr. 31/5, Moscow, Russia, 119192
4 Faculty of Physics, Lomonosov Moscow State University 1/2 Leninskie gory, Moscow, Russia, 119991
5 Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology 9 Institutskii per., Dolgoprudnyi, Russia, 141700
6 Therapeutic Faculty, Pirogov Russian National Research Medical University 1 Ostrovityanova St, Moscow, Russia, 117997
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T.O. Shepelyuk; M.A. Panteleev; A.N. Sveshnikova. Computational modeling of Quiescent Platelet Energy Metabolism in the Context of Whole-body Glucose Turnover. Mathematical modelling of natural phenomena, Tome 11 (2016) no. 6, pp. 91-101. doi : 10.1051/mmnp/201611606. https://geodesic-test.mathdoc.fr/articles/10.1051/mmnp/201611606/

[1] H.H. Versteeg, J.W. Heemskerk, M. Levi, P.H. Reitsma New fundamentals in hemostasis Physiol Rev 2013 327 358

[2] J.C. Doery, J. Hirsh, I. Cooper Energy metabolism in human platelets: interrelationship between glycolysis and oxidative metabolism Blood 1970 159 68

[3] S. Ravi, B. Chacko, H. Sawada, P.A. Kramer, M.S. Johnson, G.A. Benavides Metabolic plasticity in resting and thrombin activated platelets PLoS One 2015 e0123597

[4] S. Karpatkin Studies on human platelet glycolysis. Effect of glucose, cyanide, insulin, citrate, and agglutination and contraction on platelet glycolysis J. Clin. Invest. 1967 409 17

[5] J.W. Akkerman, H. Holmsen Interrelationships among platelet responses: studies on the burst in proton liberation, lactate production, and oxygen uptake during platelet aggregation and Ca2+ secretion Blood 1981 956 66

[6] V. Vasta, E. Meacci, M. Farnararo, P. Bruni Glutamine Utilization in Resting and Stimulated Platelets J. Biochem. 1993 163 166

[7] M. Guppy, L. Abas, C. Neylon, M.E. Whisson, S. Whitham, D.W. Pethick Fuel Choices by Human Platelets in Human Plasma Eur. J. Biochem 1997 161 167

[8] M. Guppy, M.E. Whisson, R. Sabaratnam, P. Withers, K. Brand Alternative Fuels for Platelet Storage: A Metabolic Study Vox Sang 1990 146 152

[9] M.H. Fukami, H. Holmsen, L. Salganicoff Adenine nucleotide metabolism of blood platelets IX. Time course of secretion and changes in energy metabolism in thrombin-treated platelets Biochim. Biophys. Acta - Gen. Subj 1976 633 643

[10] J.-W.N. Akkerman, G. Gorter Relation between energy production and adenine nucleotide metabolism in human blood platelets Biochim. Biophys. Acta - Bioenerg 1980 107 116

[11] S. Murphy, F.H. Gardner Platelet storage at 22 degrees C J. Clin. Invest 1971 370 7

[12] J.W. Akkerman, G. Rijksen, G. Gorter, G.E. Staal Platelet functions and energy metabolism in a patient with hexokinase deficiency Blood 1984 147 153

[13] J.W.N. Akkerman, G. Gorter, J.J. Sixma Regulation of glycolytic flux in human platelets relation between energy production by glyco(geno)lysis and energy consumption Biochim. Biophys. Acta - Gen. Subj 1978 241 250

[14] R.B. Scott Activation of glycogen phosphorylase in blood platelets Blood 1967 321 330

[15] P.W. Majerus, M.B. Smith, G.H. Clamon Lipid metabolism in human platelets. I. Evidence for a complete fatty acid synthesizing system J. Clin. Invest 1969 156 164

[16] P. Cohen, A. Derksen, H. Van Den Bosch Pathways of fatty acid metabolism in human platelets J. Clin. Invest. 1970 128 139

[17] A. Thomas, S. Rahmanian, A. Bordbar, B.Ø. Palsson, N. Jamshidi Network reconstruction of platelet metabolism identifies metabolic signature for aspirin resistance Sci. Rep. 2014 3925

[18] J.W.N. Akkerman, G. Gorter, L. Schrama, H. Holmsen A novel technique for rapid determination of energy consumption in platelets. Demonstration of different energy consumption associated with three secretory responses Biochem. J. 1983 145 155

[19] M.G. Markakis, G.D. Mitsis, V.Z. Marmarelis Computational study of an augmented minimal model for glycaemia control Conf. Proc. … Annu. Int. Conf. IEEE Eng. Med. Biol. Soc. IEEE Eng. Med. Biol. Soc. Annu. Conf 2008 5445 8

[20] J.D. Orth, I. Thiele, B.Ø. Palsson What is flux balance analysis? Nat. Biotechnol 2010 245 8

[21] J.M. Lee, E.P. Gianchandani, J.A. Papin Flux balance analysis in the era of metabolomics Brief. Bioinform 2006 140 50

[22] N. Jamshidi, B.Ø. Palsson Formulating genome-scale kinetic models in the post-genome era Mol. Syst. Biol. 2008 171

[23] A.M. Feist, M.J. Herrgård, I. Thiele, J.L. Reed, B.Ø. Palsson Reconstruction of biochemical networks in microorganisms. Nat. Rev. Microbiol. 2009 129 43

[24] J.M. Burkhart, M. Vaudel, S. Gambaryan, S. Radau, U. Walter, L. Martens The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways Blood 2012 e73 e82

[25] S. Schaller, S. Willmann, J. Lippert, L. Schaupp, T.R. Pieber, A. Schuppert A Generic Integrated Physiologically based Whole-body Model of the Glucose-Insulin-Glucagon Regulatory System CPT Pharmacometrics Syst. Pharmacol. 2013 e65

[26] P. Mendes, S. Hoops, S. Sahle, R. Gauges, J. Dada, U. Kummer Computational modeling of biochemical networks using COPASI Methods Mol.Biol. 2009 17 59

[27] T. Back, Evolutionary algorithms in theory and practice: evolution strategies, evolutionary programming, genetic algorithms, Oxford university press, Oxford, 1996.

[28] I.A. Ferreira, A.I.M. Mocking, R.T. Urbanus, S. Varlack, M. Wnuk, J.-W.N. Akkerman Glucose uptake via glucose transporter 3 by human platelets is regulated by protein kinase B. J. Biol. Chem. 2005 32625 33

[29] A. Makhorin, GNU linear programming kit, Moscow Aviat. Inst. (2001).

[30] S. Hoops, S. Sahle, R. Gauges, C. Lee, J. Pahle, N. Simus COPASI–a COmplex PAthway SImulator Bioinformatics 2006 3067 3074

[31] J.W.N. Akkerman, H. Holmsen, M. Loughnane Simultaneous measurement of aggregation, secretion, oxygen uptake, proton production, and intracellular metabolites in the same platelet suspension Anal. Biochem. 1979 387 393

[32] J.C.G. Doery, J. Hirsh, G.C. De Gruchy Platelet Glycolytic Enzymes: Effect of Cellular Disruption Procedures on Activity Br. J. Haematol. 1970 145 157

[33] J.T. Sorensen, A physiologic model of glucose metabolism in man and its use to design and assess improved insulin therapies for diabetes, (1985). http://dspace.mit.edu/handle/1721.1/15234.

[34] N. Borregaard, T. Herlin Energy metabolism of human neutrophils during phagocytosis J. Clin. Invest. 1982 550 7

[35] R.H. Unger, A.M. Eisentraut, L.L. Madison The effects of total starvation upon the levels of circulating glucagon and insulin in man J. Clin. Invest. 1963 1031 9

[36] A. Saltelli, M. Ratto, S. Tarantola, F. Campolongo Sensitivity analysis for chemical models Chem.Rev. 2005 2811 2828

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