Ionization State of Histidine Each ionizable group of an amino acid can exist in one of two states, charged or neutral. The electric charge on the functional group is determined by the relationship between its pKa and the pH of the solution. This relationship is described by the Henderson-Hasselbalch equation.

(a) Histidine has three ionizable functional groups. Write the equilibrium equations for its three ionizations and assign the proper pKa for each ionization. Draw the structure of histi- dine in each ionization state. What is the net charge on the his- tidine molecule in each ionization state?

(b) Draw the structures of the predominant ionization state of histidine at pH 1, 4, 8, and 12. Note that the ionization state can be approximated by treating each ionizable group independently.