Question

In a condition called b-thalassemia, the b globin chains are not synthesized and tetramers consisting solely of a chains form. Compare the oxygen binding behaviors of this protein and normal hemoglobin.

Answer 1

Normal hemoglobin (hemoglobin-A, the most abundant of the hemoglobins) is a tetramer $\alpha_2\beta_2$ . Both the $\alpha$ (141 amino acid residues) and $\beta$ (146 amino acid residues) subunits reversibly binds oxygen because they bind oxygen strong enough so that the complex with oxygen does not break unnecessarily but also not so strong as to form irreversible complex, otherwise oxygen delivery to tissues is not possible.

But a  $\beta$-thalassemia patient's hemoglobin consits of $\alpha$ and $\gamma$ subunits forming the tetramer $\alpha_2\gamma_2$ . Here the $\gamma$ subunit has high afinity towards oxygen resulting in a strong irreversible binding of oxygen.

The other difference between the two hemoglobins (normal $\alpha_2\beta_2$ and $\alpha_2\gamma_2$ ) is that the normal hemoglobin-A shows co-operativity and the other does not. When one of the subunits binds oxygen by its Fe2+ion, the imidazole side-chain of the distal histidine interacts to the other uncoordinated site (Before binding Fe2+ has 2 free coordination sites to complete its octahedral geometry). This creates a strain in the subunit which is transmitted to all other subunits which induces conformational shift of the tetramer unit from a tense (T) to relaxed (R) form. Which in turn induces oxygen binding to all of the subunits. This is known as cooperativity. The $\alpha_2\gamma_2$ tetramer consisting solely of chain forms does not show cooperativity. This results in an incomplete development of red blood cells causing lack of oxygen delivered to the tissues which in turn leads to poor growth, and other helath realted problems for the beta-thalassemia patients.