Formaldehyde reacts with protein side chains by combining with which group?

• A. Amino group
• B. Carboxyl group
• C. Sulfhydryl group
• D. Methyl group

Answer: (A)

Formaldehyde fixes proteins mainly by reacting with amino groups. It targets primary amino groups on proteins, especially the ε-amino groups of lysine residues and N-termini. The aldehyde first forms a hydroxymethyl adduct with the amino group, and this activated site can then react with another amino group to create a methylene bridge between two sites. This cross-linking stabilizes protein structure and tissue morphology during processing. Carboxyl groups are not the primary reactive targets in this fixation mechanism, and sulfhydryl groups can participate to a lesser extent, but the dominant chemistry involves amino groups.