Oxygen Binding to Sickle Cell Hemoglobin

This chapter describes oxygen binding to sickle-cell hemoglobin. Sickle-cell anemia was first recognized as a distinct disease in 1910, but only during the past three decades has its molecular basis been revealed in some detail. There are many single-amino-acid modifications of human hemoglobin that alter the functional properties of the tetrameric hemoglobin molecule and thereby compromise its physiological function. The abnormal properties of hemoglobin S are more complex than this. The major abnormality in hemoglobin S is a tendency for the deoxygenated molecules to polymerize into ordered fibrous structures. The fibers can themselves align side-by-side to form crystalline arrays. Because of the large numbers of molecules incorporated into these assemblies, this polymerization reaction appears to a first approximation as a phase separation and can be viewed as a limitation in the solubility of the deoxygenated hemoglobin S molecule. However, the amount of polymerization accompanying deoxygenation is strongly dependent on the total hemoglobin concentration and, therefore, the apparent oxygen affinity is also concentration dependent. The chapter further describes the preparation of hemoglobin S and hemoglobin A for comparison studies.