Question

Why do the ${\mathbf{pK}}_{\mathbf{a}}$values of ionizable groups differ between free amino acids and amino acid residues in polypeptides?

Short answer

The three-dimensional structure of the polypeptide chain brings the polar side chain, carboxyl; amino sides close together due to the electrostatic force of attraction. This shifting causes the change in${\mathrm{pK}}_{\mathrm{a}}$ values between free amino acid and amino acid residue.

Step-by-step solution

pKa value

It is defined as the ability of an acid or base to donate its protons to water. Lower the${\mathrm{pK}}_{\mathrm{a}}$ value; the acid or base will be stronger.

Free amino acid and amino acid residue

Free amino acid is composed of an amino group and a carboxyl group. Combiningone ormore amino acids forms amino acid residue, also called peptides, by eliminating water molecules. Thus, peptides don’t have free $\mathrm{\alpha }$-amino and $\mathrm{\alpha }$-carboxyl groups.

Difference between free amino acid and polypeptide

The${\mathrm{pK}}_{\mathrm{a}}$ values of amino and carboxyl groups of free amino acid and polypeptide are different. The free amino acid${\mathbf{pK}}_{\mathbf{a}}$value of the carboxyl group is lower than the carboxyl group in a polypeptide chain. This is because${\mathrm{COO}}^{-}$ group is stabilized by the ammonium group, which is positively charged. Also, the electron withdrawing nature of carboxyl group gives the amino group of free amino acids a higher${\mathrm{pK}}_{\mathrm{a}}$ value.

The electrostatic force of attraction in polypeptide brings the polar straight chain and the C and N-termini close together to shift the${\mathrm{pK}}_{\mathrm{a}}$ value from the corresponding${\mathrm{pK}}_{\mathrm{a}}$ values of free amino acid.