Hypoxic Response Of Human Red Blood Cell Metabolism

We analyzed time-course-metabolomics of red blood cell under conditions of normoxia and hypoxia by a high-throughput metabolomics technology using a capillary electrophoresis coupled with mass spectrometry (CE/MS). To understand the differences in hypoxic and normoxic conditions, we developed a simulation model of metabolism in red blood cell. It covers major metabolic pathways in human red blood cells including glycolytic pathway, pentose phosphate pathway, adenine nucleotide metabolism and membrane transport systems. It also considers the oxygen saturation of intracellular hemoglobin and varies according to oxygen level change and binding interactions of hemoglobin with several metabolites. The comparison between in vitro metabolome data and in silico simulation results both revealed that the activity of glycolysis can be significantly increased under hypoxia and the role of band3 protein to explain the metabolic changes under hypoxia. Simulation results and experimental validations further suggested the possibility that red blood cells act as one of the local oxygen sensors and have vasodilatory effects in hypoxia by regulating metabolic activities. Band3 may be the key to the immediate and drastic switching of metabolic effects.