Computational modeling of Quiescent Platelet Energy Metabolism in the Context of Whole-body Glucose Turnover

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

^* Corresponding author. E-mail: agolomy@gmail.com

Abstract

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.