The Mechanism of Interaction of Red Cell Organic Phosphates with Hemoglobin

Abstract

Oxygen release depends crucially both on the shape of the oxygen binding curve and on the overall oxygen affinity. This chapter overviews the interaction of organic phosphates with hemoglobin, D-2, 3-diphosphoglycera (DPG) and the Bohr effect, DPG and CO2 transport, effect of DPG on abnormal hemoglobins, and organic phosphates and artificial hemoglobin hybrids. Human hemoglobin without organic phosphates binds oxygen far too tightly to release it under physiological conditions. The large intracellular concentration of DPG lowers the oxygen affinity into the useful range, where it is further modulated by organic phosphates, hydrogen ions, and CO2. The red cell DPG level is subject to metabolic control, including feedback mechanisms, which respond to oxygen requirement. On a molecular level, the basis for the lowering of the oxygen affinity by organic phosphates is their mole for mole interaction with a single site on deoxyhemoglobin, which is destroyed on ligand binding. The linkage of phosphate cofactors with ligand binding also adds a new dimension to studies on the mechanism of oxygen transport by hemoglobin and models for the mechanism of oxygenation must take account of the influence of these cofactors. The specific stabilization of the deoxy conformation by organic phosphates has provided a powerful tool for investigations on the conformational transitions, which are basic for the understanding of the mechanism of oxygenation.