Sphingosine-1-phosphate and Adenosine affects the oxygen dependence of erythrocyte metabolism

Human erythrocyte metabolism (glycolysis and Pentose Pathway) is modulated by the cell oxygenation state. Among other mechanisms, competition of deoxyhemoglobin and some glycolytic enzymes for the cytoplasmic domain of band 3 is involved in modulation. This metabolic modulation is connected to variations in intracellular NADPH and ATP levels as a function of the oxygenation state of the cell, and, consequently, it has physiologic relevance. The present study investigates the effect of sphingosine-1-phosphate (S1P) and Adenosine exposure on this metabolic modulation. We show that both S1P and Adenosine promote deoxygenated Hb anchoring to the membrane; this event enhances the release of membrane-bound glycolytic enzymes to the cytosol, inducing glycolysis with respect to pentose pathway (PPP). As a result, metabolic differences between erythrocytes incubated at high and low oxygen saturation increase following to exposure to both sphingosine-1-phosphate (S1P) and Adenosine. Our findings suggest a novel signaling network regulating the oxygen-dependent metabolic modulation.