Heme stability in the human embryonic hemoglobins.

The three human embryonic hemoglobins undergo both monomolecular and nucleophile stimulated bimolecular oxidations. Azide acts as an efficient nucleophile for the oxidative process in which the three embryonic hemoglobins exhibit lower oxidation rates than the adult protein. The absolute rates of azide-induced oxidation together with the rates of spontaneous autooxidation correlate with the previously determined oxygen affinities of the embryonic hemoglobins. The pH dependence of the rates of oxidation and their chloride ion concentration dependence are discussed. Heme exchange to human serum albumin has been used to determine the relative binding constants for heme for each of the embryonic proteins. Rate data have also been employed to evaluate the tetramer-dimer equilibrium constant for each hemoglobin. Overall, the data indicate that the high oxygen affinity human embryonic hemoglobins are significantly less susceptible to anion-induced oxidation, and the heme groups in each of the embryonic globin proteins are more tightly bound than in the corresponding adult protein.