Functional abnormalities of hemoglobin Toyoake (142 (H20)beta, Ala leads to Pro).

Oxygen equilibrium of Hb Toyoake (142 (H20)beta, Ala leads to Pro) is characterized by an oxygen affinity 6-times higher than that of Hb A, a slightly decreased alkaline Bohr effect, diminished cooperativity, with Hill's coefficient decreased by 1.2, and reduced response to 2,3-diphosphoglycerate and inositol hexaphosphate. These properties are in qualitative agreement with those shown previously from oxygen equilibrium data for hemolysate containing Hb Toyoake. The heat of oxygenation was -13.5 kcal/mol for Hb Toyoake and -12.9 kcal/mol for Hb A at pH 7.4 in 0.1 M Cl- and they became equal when corrected for the heat of oxygen-linked proton and Cl- release. OxyHb Toyoake autooxidized faster than oxyHb A. The visible absorption spectrum and electron paramagnetic resonance spectrum of oxidized Hb Toyake indicated that oxidation of this hemoglobin, either by autooxidation or by K3Fe(CN)6, is followed by gradual conversion into hemichrome derivatives. The soret peak of deoxyHb Toyoake was lowered compared to that of deoxyHb A and the magnitude of narrow-banded oxy-minus-deoxy difference spectrum around 290 nm was smaller for Hb Toyoake than for Hb A, indicating that the former remains predominantly in the R state upon deoxygenation. The functional abnormalities, including tendency to lose heme groups previously reported, were interpreted in terms of structural disturbance by proline at 142beta of 141 leucine, 143 histidine, 145 tyrosine, and 146 histidine residues of the same beta chain.