The Bohr Effect

Abstract

The control of oxygen binding by hemoglobin (Hb) with pH is of profound importance in facilitating gas exchange in blood. This modulation, known as the Bohr effect, reflects the fact that protons are released upon Hb oxygena­ tion at physiological pH (the alkaline Bohr effect), and protons are taken up upon oxygenation at low pH (the acid or reversed Bohr effect). Reciprocally, changes in pH modulate oxygen affinity. These proton exchanges arise because conformational changes in the Hb associated with ligand binding at the heme result in pK changes in certain acid groups that are distant from the heme. Changes in proton binding also result from differential interaction of buffer ions with oxyand deoxy-Hb (3, 18). The binding of salt ions can be considered a special kind of Bohr effect (3). Resonance Raman spectroscopy shows that the iron-proximal histidine stretching motion is exquisitely sensi­ tive to amino acid substitutions distant from the heme (34). This review examines recent experiments to determine which groups are responsible for the Bohr effect and how these ligand-linked processes are modulated by other allosteric factors, e.g. buffer ions, organic phosphates, CO2, and chloride, all of which lower the oxygen affinity of Hb by preferential binding to deoxy-Hb. A central problem has been to determine the relative quantitative roles of different ionizable groups responsible for in the Bohr effect. What kinds and numbers of groups are involved? Attempts have been made to calculate pK values by using electrostatic theory. How do such electrostatic calculations compare with other methods for estimating the contributions of different groups?