Self-association of hemoglobin β SH chains is linked to oxygenation

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Abstract
Self-association of unliganded .beta.SH chains [from human Hb] into tetramers (4 .beta.1 .dblarw. .beta.4) was experimentally found to be energetically less favorable (.DELTA.G0 = -19.05 .+-. 0.30 kcal) than the corresponding oligomerization of fully oxygenated chains (4.beta.1X .dblarw. .beta.4X4; .DELTA.G0 = -22.45 .+-. 0.35 kcal). The tetramers must bind O2 with a higher affinity than that of dissociated chains. Calculations are presented showing why this affinity difference is not easily detected. The linkage is in a direction opposite to that exhibited by normal Hb A, in which oligomerization of high-affinity unliganded dimers (2 .alpha..beta. .dblarw. .alpha.2.beta.2) leads to tetramers with decreased O2 affinity. In contrast, the oligomerization of high-affinity, unliganded .beta.SH chains leads to tetramer with even higher affinity. The existence of at least 2 conformational states for .beta. chains is implied. Effects of inositol hexaphosphate on .beta. chain association were investigated. Inositol hexaphosphate had no measurable effect at pH 7.4, in contrast to pH 7 where very pronounced effects were observed. Some theoretical aspects of the linkages were presented and the relationship of the findings to concepts of structural transition and allosteric regulation was discussed.