MUTANT HEMOGLOBINS (ALPHA(119)-ALA AND BETA(55)-SER) - FUNCTIONS RELATED TO HIGH-ALTITUDE RESPIRATION IN GEESE

The unusually high blood-O-2 affinity in the bar-headed and Andean gee se is a necessary adaptation for migration across high mountain ranges . The amino acid residues alpha-119 and beta-55, which form an alpha 1 beta 1 contact in human hemoglobin (Hb), are altered in bar-headed an d Andean geese, respectively, which suggests that loss of this contact increases O-2 affinity. Two mutant human Hbs with equivalent mutation s at these sites prepared by site-directed muta genesis show the same increase in O-2 affinity compared with Hb A, which indicates that thes e mutations are responsible for the changes in the protein. The intrin sic affinity difference compared with native Hb A is amplified by orga nic phosphates. Whereas the recombinant and native Hbs displayed simil ar sensitivities to pH, chloride, and 2,3-diphosphoglycerate, the oxyg enation heat of the alpha-chain mutant decreased in the presence of 2, 3-diphosphoglycerate. O-2 association constants for the deoxygenated s tate of the alpha-mutant were about three times those for Hb A. The mu tant Hb analogously exhibited higher affinity constants for binding th e first three O-2 molecules. Calculated heme-heme interaction energies indicated that loss of a single contact, resulting in destabilization of the deoxy (tense) structure, underlies the increased O-2 affinity. Adaptations securing Hb-O-2 binding at extreme altitude are discussed .