denaturation

Meaning: Denaturation is the loss of a protein's native three-dimensional shape. Heat, extreme pH, urea, detergents such as SDS, and organic solvents disrupt the noncovalent forces (hydrogen bonds, ionic interactions, hydrophobic effects) that hold secondary, tertiary and quaternary structure. Reducing agents such as β-mercaptoethanol also break disulfide bonds. Peptide bonds stay intact, so primary structure is preserved. Because function depends on shape, an enzyme usually loses activity when denatured.

On the MCAT: Expect an activity-versus-temperature or activity-versus-pH graph that falls sharply past the optimum, with a question asking why. Anfinsen's ribonuclease experiment is the classic design: urea and β-mercaptoethanol unfolded the enzyme and abolished activity, and removing them let it refold and regain activity, showing that the primary sequence can specify the fold. In SDS-PAGE, SDS denatures proteins so they separate mainly by mass.

Common confusion: Denaturation is not hydrolysis of peptide bonds. Breaking those bonds needs a protease or strong acid with heat, and it destroys primary structure. Denaturation is also not always permanent: cooked egg white stays unfolded, but small proteins such as ribonuclease can refold once the denaturant is removed.