REGULATION OF OXYGEN-AFFINITY OF HEMOGLOBIN - INFLUENCE OF STRUCTURE OF THE GLOBIN ON THE HEME IRON

The main theme is the regulation of the oxygen affinity of the heme by the structure of the globin. In principle, this could be accomplished by inductive effects. For instance, there exists an abnormal hemoglobin in which an alanine in the heme pocket is replaced by an aspartate (Ala E14β→Asp). This Hb has an abnormally low oxygen affinity, apparently because the negative field generated by the carboxylate group opposes the formation of the iron-linked superoxide anion. However, analysis of the structures of normal Hb and Mb suggest that steric rather than inductive effects are dominant. They influence both the change in Fe-N bond lengths accompanying the transition from the high-spin five-coordinated deoxy to the low-spin six-coordinated oxy form and, by steric hindrance, the actual presence of the oxygen molecule at its binding site. Therefore, the physical basis of heme-heme interaction is mechanical rather than inductive.