PROPERTIES OF HEMOGLOBIN M, MILWAUKEE-I VARIANT AND ITS UNIQUE CHARACTERISTIC

The physicochemical properties of Hb M Milwaukee-1 (α2β267Glu) were studied in comparison with other Hb M variants and Hb Sydney (α2β267Ala). Using the patient's blood containing Hb M Milwaukee-1. EPR spectra with high-spin-type signals were revealed which resembled those of Hb M Saskatoon indicating that the glutamic acid residue at E 11 has an effect on the heme iron analogous to the tyrosine residue at E7. In an O2 equilibrium study, Hb M Milwaukee-1 showed a diminished heme-heme interaction, 1.4-1.6 in terms of n value, and this value seemed to be dependent on pH or temperature. Although the affinity for O2 was as low as about 60 mm Hg of P50 at pH 6.5, the Bohr effect was distinctly present in this Hb M, and its magnitude was larger than that of Hb A. The effect of temperature on the O2 affinity, however, was significantly smaller in this Hb M than that observed in Hb A. In contrast to Hb Sydney, Hb M Milwaukee-1 was as stable as Hb A in an heat denaturation experiment, reflecting the stabilizing effect of the intramolecular bonding between the ferric heme iron and the substituted glutamic acid residue on the whole molecule. © 1969.