Which amino acid has an imidazole side chain that participates in acid-base catalysis at physiological pH?

• A. Glycine
• B. Proline
• C. Histidine
• D. Valine

Answer: (C)

Acid-base catalysis in enzyme active sites relies on amino acid residues whose side chains can gain or lose protons near physiological pH. Histidine fits this role because its imidazole side chain has a pKa around 6.0, so at about pH 7 it exists in a balance of protonated and deprotonated forms. This makes it able to act as both a proton donor and a proton acceptor during catalysis, helping to activate substrates, stabilize transition states, or shuttle protons within the active site. The other options lack an ionizable side chain at physiological pH: glycine has only a hydrogen side chain, proline’s ring makes its nitrogen less available for proton transfer, and valine is hydrophobic with no ionizable group. Thus, the imidazole-containing histidine is the best fit for acid-base catalysis at physiological pH.