Polycythemia Associatedwith a Hemoglobinopathy 815 a - N ( Bart ' S ) I a - Ho 2 a - Ches I a - Gssg Aa B . . . S - C Agr Starch Gel Hemoglobin Chesapeake

The efficiency of hemoglobin as an oxygencarrying substance is dependent upon certain features of its molecular configuration. The functional integrity of the molecule depends not only on spatial relationships between the heme and globin moieties, but on interrelations between the four globin chains (1, 2). The functional significance of portions of the molecule can be investigated by a study of hemoglobin with known abnormalities of structure. Many structural abnormalities have been reported, but functional abnormalities are extremely rare. Despite considerable differences in the amino acid composition of the fi, 8, and y chains, the oxygen dissociation curves of purified solutions of hemoglobin A (a2Ih8), hemoglobin F (ay,), and hemoglobin A2 (a282) are quite similar (3-5). In contrast, hemoglobins H (/4), Bart's (y,), and aA, in which interaction between a and , chains is impossible, have very high oxygen affinities (1, 2, 6). A Bohr effect is not present, and oxygen dissociation curves are hyperbolic rather than sigmoid in shape, indicating that heme-heme interactions are absent. Hemoglobin A treated with carboxypeptidase A also exhibits increased oxygen affinity and absence of heme-heme interactions (7). Altered oxygen affinity is thought to be a nonspecific result of inability of this modified hemoglobin to undergo a conformational change on deoxygenation. Other abnormal hemoglobins with altered oxy-