Functional characterization of fetal and adult yak hemoglobins: an oxygen binding cascade and its molecular basis.

In contrast to most other mammals, the yak, which is native to high altitudes, has two major fetal and two or four major adult hemoglobin (Hb) components. We report the oxygen affinities and sensitivities to pH and 2,3-diphosphoglycerate of the two fetal and two adult Hbs commonly found in calves, compared to those of adult cow Hb A, and relate these findings to their primary structures and to placental maternal-fetal oxygen transfer at altitude. Arranged in order of decreasing oxygen affinity the Hbs are F1 (alpha I2 gamma 2), F2 (alpha II2 gamma 2), A1 (alpha II2 beta II2), and cow Hb A. The higher affinity of the fetal than the adult yak Hbs correlates with the beta 15Trp----Phe substitution, whereas the higher affinity in yak than in cow Hb correlates with the beta 135Ala----Val substitution. The difference in oxygen affinities between yak Hbs A1 and A2, which have identical beta chains, suggests the existence of yet unknown mechanisms determining oxygen affinity. The larger Bohr effects of F2 than F1 and of A2 than A1 are attributable to alpha-chain differences, most probably the alpha I50Glu----alpha II50His substitution.