Computational modeling of quiescent platelet energy metabolism in the context of whole-body glucose turnoverстатья
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Дата последнего поиска статьи во внешних источниках: 11 марта 2017 г.
Аннотация: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
uxes 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.