Can Metabolites Contribute in Regulating Blood Oxygen Affinity?

Abstract

There are a number of interrelated factors contributing to the regulation of blood oxygen affinity in animals. The red blood cell in mammals has an active glycolytic system and a relationship exists between metabolism and function of the red cell in oxygen transport during hypoxia. The relationship in red cells of most mammals involves binding of 2,3-bisphosphoglycerate (2,3-P₂-glycerate), a glycolytic intermediate, with deoxyhemoglobin, regulating Hemoglobin function and enhancing oxygen delivery to the tissues (Benesch and Benesch, 1967; Chanutin and Curnish, 1967). The in vivo level of 2,3-P₂-glycerate in human erythrocytes increases above normal during hypoxia from altitude or from certain pathological conditions, but no satisfactory way is known to actually manipulate the in vivo concentration of this compound. In human erythrocytes, the levels of 2,3-P₂- glycerate and ATP, which also influences hemoglobin binding, can be depleted after in vitro incubation at 37° for 12-24 hours (Lian et al., 1971); red cells incubated with glycolate also lose 2,3-P₂-glycerate rapidly without changes in ATP concentrations (Rose, 1976). The level of 2,3-P₂- glycerate can be enriched several-fold in human red cells by incubating with inosine, pyruvate, and inorganic phosphate (Lian et al., 1971). Importantly, during the depletion and enrichment of the cells 2,3-P₂-glycerate levels, there is a corresponding increase and decrease in blood oxygen affinity (Lian et al., 1971). Further, the allosteric properties of hemoglobins are such that increases in [H⁺], CO₂ and temperature, features which are all present in tissue capillary beds, also facilitate the release of oxygen.