On the mechanisms of the hypoxia-induced increase of 2,3-diphosphoglycerate in erythrocytes. Studies on rat erythrocytes in vivo and on human erythrocytes in vitro.

Abstract

Hypoxia induces in rats a rather rapid increase of the concentration of 2,3-DPG in red blood cells. This increase is reversed when the animals are returned to normal conditions. Pigeons do not respond to hypoxia with an increase of inositol hexaphosphate concentration in their erythrocytes. In rats exposed for 24 h to gas mixtures containing low oxygen and in addition 5% CO2 the hypoxia induced rise of 2,3-DPG concentration is abolished. The hemoglobin concentration in whole blood is negatively correlated to red cell 2,3-DPG levels in normal as well as in anemic or polycythemic rats. The rate of 2,3-DPG decomposition in human erythrocytes incubated without glucose is the same in the presence and in the absence of oxygen. The incorporation of32P into 2,3-DPG proceeds faster in deoxygenated than in oxygenated human red blood cells and exceeds considerably the concomitant acceleration of the glycolytic flux rate. These findings indicate that the rate of 2,3-DPG synthesis becomes enhanced in deoxygenated cells. This is mainly due to an elevation of the intracellular pH; the relief of product inhibition of DPG mutase brought about by a greater binding of 2,3-DPG to deoxyhemoglobin seems to be of minor importance. The regulation of 2,3-DPG concentration by the intraerythrocytic pH as well as by the oxygenation state of hemoglobin and the significance of these regulatory mechanisms in inducing and limiting the changes of red cell 2,3-DPG during hypoxia and anemia are discussed.