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The Hemoglobin Molecule

Hemoglobin is the oxygen-carrying component of RBCs[47]. This tetrameric protein is comprised of two a -globin chains and two b -globin chains (Hb; a2bA2). Each globin chain is a polypeptide folded to protect a heme moiety (protoporphorin ring with an iron(Fe) prosthetic group for binding molecular oxygen (O2) and other ligands (carbon dioxide;CO2[48] and nitric oxide;NO)[49]). Each globin chain with its resident heme group is referred to as a subunit or monomer of  the Hb protein. The monomers can combine to form dimers. Under normal conditions the a- and b-globin chains are co-ordinately expressed in adult RBCs and they combined in a balanced fashion (2:2) to produce the Hb tetramer (a2b2)[50]. The process of subunit assembly  into Hb proceeds in the following manner:                                                                            

Reaction 1. a-subunit + b-subunit ab dimer.

Reaction 2. ab dimer + ab dimer a2b2; Hb.

In reaction 1, dimer assembly occurs via an electrostatic interaction between the net positively charged a-globin subunit and the net negatively charged b-globin subunit[51]. Following this, in reaction 2, the dimers combine to form the functional Hb tetramer[50]. In normal adult RBCs Hb A(a2bA2) is produce. In forming the Hb molecule, important intra-molecular interactions occur allowing for the co-operative binding  (and unloading) of O2. The general mechanism of Hb assembly and structure, with its functional implications, are similar for all Hb S.