A human hemoglobin with lowered oxygen affinity and impaired heme-heme interactions.

The reactivity of the iron in the four hemes of the mammalian hemoglobin molecule depends largely on the interactions between the prosthetic groups and the amino acid chains of the globin (1, 2). Normal configuration of heme groups in the abnormal human hemoglobins, therefore, does not preclude anomalies of their oxygen affinity which might arise from aberrations in the globin. In most of the more than 20 recognized abnormal human hemoglobins the amino acid abnormality does not affect the oxygen affinity. Amino acid changes which are remote from groups crucial in the globin-heme interaction do not affect oxygenation. Abnormal oxygen affinities have been reported in hemoglobin H and M. Hemoglobin H contains only the beta and not the alpha chains of normal hemoglobin and exhibits an oxygen affinity ten times greater than normal but has no Bohr effect (3). Hemoglobin M causes cyanosis apparently due to its inability to combine with oxygen. The pigment may be present in the blood as methemoglobin M or as its nonoxidized precursor (4). We have recently encountered a hemoglobin which caused cyanosis due to an abnormally low oxygen affinity. The entire oxyhemoglobin dissociation curve was markedly shifted, but at sufficiently high oxygen tensions the pigment became fully saturated. The oxygen equilibria, spectroscopic and preliminary electrophoretic findings are presented. Since a lowered oxygen affinity of hemoglobin is usually not considered in the differential diagnosis of cyanosis, some reference is made to the methods which lead to its detection.