Chapter 17, Problem 126AP

Histidine is one of the 20 amino acids found in proteins. Shown here is a fully protonated histidine molecule, where the numbers denote the $\text{p}{K}_{\text{a}}$, values of the acidic groups:

(a) Show stepwise ionization of histidine in solution. (Hint: The ${\text{H}}^{\text{-}}$ ion will first come off from the strongest acid group followed by the next strongest acid group and so on.) (b) A dipolar ion is one in which the species has an equal number of positive and negative charges. Identify the dipolar ion in part (a), (c) The pH at which the dipolar ion predominates is called the isoelectric point, denoted by pI. The isoelectric point is the average of the $\text{p}{K}_{\text{a}}$ values leading to and following the formation of the dipolar ion. Calculate the pI of histidine. (d) The histidine group plays an important role in buffering blood (the pH of blood is about 7.4). Which conjugate acid base pair shown in part (a) is responsible for maintaining the pH of blood?