Hb Toyoake: β142 (H20) Ala → Pro. A New Unstable Hemoglobin With High Oxygen Affinity

Abstract

AbstractA new unstable hemoglobin with high oxygen affinity. Hb Toyoake: β 142 (H20) Ala → Pro, was found in a Japanese male with a normal blood hemoglobin level, shortened red cell survival, and increased plasma erythropoietin. Hemoglobin studies showed heat and isopropanol instability, and an increased tendency to heme loss and to subunit dissociation. Electrophoresis of whole hemolysate showed inconstant abnormal bands with reduced mobilities due to progressive heme loss during the in vitro procedure. Isolated Hb Toyoake with normal heme content migrated slightly faster than HbA. Oxygen affinity of red cells was elevated with P50 of 17.0 mm Hg at pH 7.4 and 37°C (normal 25.0 mm Hg). Studies on hemolysate implied that Hb Toyoake had an almost normal Bohr effect, a diminished cooperativity, and a reduced response to inositol hexaphosphate. These multiple abnormalities are associated with a substitution of Pro for β 142 Ala, resulting in disruption of the H-helix and the adjacent C-terminal portion of β chain, which contain residues crucial for normal oxygen binding.