BACKGROUND
Hemoglobin (Hgb) is a 66.7 kDa protein coupled to four iron-binding, methene-linked tetrapyrrole rings (heme). The alpha (16p13.3; 5'-zeta-pseudozeta-pseudoalpha2-pseudoalpha1-alpha2-alpha1-theta1-3') and beta (11p15.5) globin loci determine the basic Hgb structure. The globin portion of Hgb consists of two alpha chains and two beta chains arranged in pairs forming a tetramer. Each of the four globin chains covalently associates with a heme group. The bonds between alpha and beta chains are weaker than between similar globin chains, thereby forming a cleavage plane that is important for oxygen binding and release. High affinity for oxygen occurs upon relaxation of the alpha1-beta2 cleavage plane. When the two alpha1-beta2 interfaces are closely bound, Hgb has a low affinity for oxygen. 97% of total circulating hemoglobin contains two alpha chains plus two beta chains (Hb A). Two gamma chains together with two alpha chains constitute fetal hemoglobin (Hb F). Two alpha chains plus two delta chains constitute adult hemoglobin (Hb A-2). Hb F and Hb A-2 together comprise the remaining 3% of adult hemoglobin.