Familial secondary erythrocytosis due to increased oxygen affinity is caused by destabilization of the T state of hemoglobin Brigham (α2β2Pro100Leu)

摘要: Hemoglobin Brigham (β Pro100 to Leu) was first reported in a patient with familial erythrocytosis. Erythrocytes of an affected individual from the same family contain both HbA and Hb exhibit elevated O2 affinity compared normal cells (P50 = 23 mm Hg vs. 31 mmHg at pH 7.4 37°C). affinities measured for hemolysates were sensitive changes or chloride concentrations, indicating little change Bohr Chloride effects. separated by nondenaturing cation exchange liquid chromatography, amino acid substitution verified mass spectrometry. The properties isolated patient's blood then those recombinant expressed Escherichia coli. Kinetic experiments suggest that rate constants ligand binding release high (R) low (T) quaternary states are similar native hemoglobin. However, mutation decreases T R equilibrium constant (L) which accelerates switch state during deoxy-Hb, increasing association approximately twofold, decelerates dissociation HbO2, decreasing twofold. These kinetic data help explain characteristics provide further evidence importance contribution intersubunit contacts stabilization structure.