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Archita Biswas Pawan K Dhar Girja Kaushal Kalaiarasan Ponnusamy

Abstract

Red blood cells (RBCs) form the bulk of the blood volume for delivering oxygen and nutrients to various cells in the body. Several studies have focused on the RBCs to understand its metabolic activities in normal and abnormal conditions. However, an integrated view of the red blood cell, as a system of molecular fluctuations, is still lacking. The RBC metabolic wiring comprises of four key pathways i.e. Glycolysis, Pentose Phosphate, Purine salvage pathway and Glutathione pathway. Here we present an integrated metabolic pathway model of the human red blood cell by including first three pathways due to their significant presence and interaction. Furthermore, the stochastic model of RBCs metabolic pathways has been extended to include explaining abnormal conditions in the form of Pyruvate Kinase and Aldolase A deficiencies. By studying metabolite changes insilico, four biomarkers were found to represent two genetic mutations i.e., 2-phosphoglycerate & phosphoenol pyruvate changes for Pyruvate kinase deficiency and fructose-1-6-bisphosphate & xylulose-5-phosphate for Aldolase A deficiency. The virtual RBC model has potential for more clinical applications and can be scaled up to include additional regulatory and metabolic content.

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