Robin W. Briehl

Oxygen equilibria were measured on a number of human hemoglobins, which had been "stripped" of organic phosphates and isolated by column chromatography. In the presence of 2 x 10(-4) M 2,3-diphosphoglycerate (2,3-DPG), the P(50) of hemoglobins A, A(2), S, and C increased about twofold, signifying a substantial and equal decrease in oxygen affinity. Furthermore, hemoglobins Chesapeake and M(Milwaukee-1) which have intrinsically high and low oxygen affinities, respectively, also showed a twofold increase in P(50) in the presence of 2 x 10(-4) M 2,3-DPG. In comparison to these, hemoglobins A(IC) and F were less reactive with 2,3-DPG while hemoglobin F(I) showed virtually no reactivity. The N-terminal amino of each beta-chain of hemoglobin A(IC) is linked to a hexose. In hemoglobin F(I) the N-terminal amino of each gamma-chain is acetylated. These results suggest that the N-terminal amino groups of the non-alpha-chains are involved in the binding of 2,3-DPG to hemoglobin.

We describe how twist could play an essential role in stabilizing 20 nm diameter sickle hemoglobin fibers. Our theory successfully reproduces the observed variation of helical pitch length with fiber diameter. With no remaining adjustable parameters it also yields a prediction for the torsional rigidity of sickle hemoglobin fibers that is in good agreement with experiment and hence retains the striking feature that such fibers can be highly mechanically anisotropic, even with a ratio of bending to torsional rigidity of about 50. We discuss how our study might be relevant to the development of treatment strategies.