Question

Explain how the pH at which the iron is released from the protein relates to the pKa of the protein ligands.

Answer 1

the pH at which the iron is released from the protein relates to the pKa of the protein ligands :

Change in pH changes charge on protein or peptide chains. A reduction in pH will decrease no. of side chains with -ve charge ( -COO- + H+ <===> -COOH ) , and increses no. of positive charged side chains ( -NH2 + H + ===> -NH3+ ).

In the case of transferrin reduction in pH induces the release of iron from it, it occurs by a process that involves a conformational change in the protein from a closed to an open form. It suggests that there must be changes in the protonation states of certain residues in the protein accompanying this conformational change. Such changes in protonation states of residues and the consequent changes in electrostatic interactions are assumed to play a large part in the mechanism of release of iron from transferrin.

Changes in the protonation states of amino acid residues depends upon pKa of side chain, since side chain groups acts as protein ligands , like : His-Imidazole ; Cys-S- ; Asp/Glu : -COO-  ; Tyr-O- etc. If change in pH will change the protonation states of protein ligand , it will release Iron from binding side, this pH will depends on pKa . ( when pH = pKa : corresponding group is in equal amounts in both states. )