Human serum albumin, the most abundant blood protein, has multiple roles, including acting as a buffer to help maintain blood pH. Albumin can act as a buffer because of which one of the following?

The side chains of the amino acid residues in proteins contain functional groups with different pKa values. Therefore, they can donate and accept protons at various pH values and act as buffers over a broad pH spectrum. There is only one N-terminal amino group (pKa 9) and one C-terminal carboxyl group (pKa 3) per polypeptide chain. At physiologic pH, these groups would not be accepting or donating protons because the amino terminal group would always be protonated, and the carboxyl terminal carboxylic acid would always be deprotonated. Peptide bonds are not readily hydrolyzed, and such hydrolysis would not provide buffering action. Hydrogen bonds have no buffering capacity because the hydrogen in these bonds is not donated or accepted once the bond is formed.