Justify all answers (show all work).1. Minor changes in primary structure can have pronounced effects on biological function. Tetramerichemoglobin, a₂³₂, dissociates into pairs of dimers aß to different extents depending on the protein primarystructure. The standard Gibb energies of dissociation of normal adult hemoglobin A and of several mutantshave been determined and are listed in the table below.Substitution in mutantHemoglobinA, normalRichmondKansasGeorgia102B; Asn → Thr102B; Asn → Thr95x; Pro → LeuAG® of dissociation (kcal/mole Hb)8.26.0655.13.6(a) Write an equilibrium expression for the dissociation of hemoglobin tetramer into dimers.(b) For normal hemoglobin and its three mutants (variations) calculate the equilibrium constant for theirdissociation from a tetramer into dimers.(c) How do the equilibrium constants for the dissociation of the hemoglobin mutants compare to that ofnormal hemoglobin?

Hemoglobin is a tertameric protein made up of 4 subunits namely α2β2. The αβ form a dimer and 2 such dimers make up the tetramer. Each subunit is attached to one heme group. Heme is responsible for the red coloration of the protein. Also, one heme binds to one O2 molecule.The dissociation of hemoglobin tetramer into dimers is given by the reaction:α2β2→2αβThe equilibrium constant for the reaction K is given by:K=αβ2α2β2where,αβ= concentration of Hb dimerα2β2= concentration of Hb tetramerThe relation between standard free energy change and equilibrium constant is given by:Δ°G=-RTlnKwhere,Δ°G= standard free energy changeR= universal gas constantT=temerature in KelvinK=equilibrium constant1. The K of normal Hb is:K=e-Δ°GRTconsidering T=298K and R=1.987×10-3 kcal/mol K and Δ°G=8.2 kcal/molK=e-8.21.987×10-3×298=1.146×10-62. For richmond Hb:K=e-6.01.987×10-3×298=3.975×10-53. for kansas Hb:K=e-5.11.987×10-3×298=1.187×10-44. for Georgia Hb:K=e-3.61.987×10-3×298=2.289×10-3The highest value of K for Georgia Hb suggests that its dissociation is more favorable than the rest. It may also indicate that the Proline residue in the 95th position on the alpha chain is crucial for the association of subunits into a tetramer. A point mutation of which can increase the chances of dissociation of Hb tetramer into dimers by a factor of 103. The lowest value of normal Hb suggests that the tetrameric structure is more favorable than the dimer.