Molecular pathology of hemoglobin M Saskatoon disease

Absorption spectra of erythrocyte hemolysate from a normal subject, the Hemoglobin (Hb1) M Saskatoon patient and the Hb M Boston patients were investigated. Difference spectrum between the hemolysate from either freshly obtained or 37 degrees C-incubated blood of the Hb M Saskatoon patient and that of the normal blood suggested that about 50% of the abnormal chain were in the ferrous state in the patient's blood. In contrast, no abnormal chain containing the ferrous heme was detected in the hemolysate from the fresh blood of the Hb M Boston patient. Resonance Raman (RR) studies indicated that methemoglobin (metHb) M Saskatoon with a weak Fe-tyrosinate interaction contained the six-coordinate heme like normal metHb A whereas metHb M Boston had the five-coordinate heme. Studies on effects of pH on absorption and RR spectra of these three hemoglobins suggested that the coordinated tyrosinate in the abnormal chain of Hb M Saskatoon was dissociated at pH 5.0. This unique heme structure of Hb M Saskatoon may relate to the susceptibility for the reduction by erythrocyte methemoglobin reductases, which is responsible for mild cyanosis of Hb M Saskatoon disease.