For basic amino acids, how is the isoelectric point calculated?

For basic amino acids, how is the isoelectric point calculated?

• A. The average of the pKa values of the amino group and the side-chain amino group.
• B. The average of the carboxyl group and the side-chain carboxyl pKa.
• C. The pKa of the amino group alone.
• D. The pH at which the side chain is deprotonated.

Answer: (A)

Isoelectric point is the pH at which a molecule has no net charge. For basic amino acids, the two groups that control charge around that neutral state are the α-amino group and the side-chain amino group. The carboxyl group deprotonates early (at a low pH) and gives the molecule a positive charge that is then balanced only after the amino groups start losing protons as the pH rises. The pI falls between the pKa values of the two groups whose protonation states determine the transition from a positive overall charge to zero and then to negative as pH increases. Therefore, the pI is the average of the pKa values of the α-amino group and the side-chain amino group. This is why the correct approach is to take the mean of those two pKa values. For context, lysine or arginine have two relevant amino-group pKa values around 9–12, so their pI is roughly midway between them; the exact numbers depend on the specific amino acid.

Isoelectric point is the pH at which a molecule has no net charge. For basic amino acids, the two groups that control charge around that neutral state are the α-amino group and the side-chain amino group. The carboxyl group deprotonates early (at a low pH) and gives the molecule a positive charge that is then balanced only after the amino groups start losing protons as the pH rises. The pI falls between the pKa values of the two groups whose protonation states determine the transition from a positive overall charge to zero and then to negative as pH increases. Therefore, the pI is the average of the pKa values of the α-amino group and the side-chain amino group. This is why the correct approach is to take the mean of those two pKa values. For context, lysine or arginine have two relevant amino-group pKa values around 9–12, so their pI is roughly midway between them; the exact numbers depend on the specific amino acid.