MCAT Biochemistry Review

Chapter 1: Amino Acids, Peptides, and Proteins

1.6 Denaturation

In the previous section, we discussed protein folding. The reverse of this process is denaturation, in which a protein loses its three-dimensional structure. Although it is sometimes reversible, denaturation is often irreversible; whether its denaturation is reversible or not, unfolded proteins cannot catalyze reactions. The two main causes of denaturation are heat and solutes.

As with all molecules, when the temperature of a protein increases, its average kinetic energy increases. When the temperature gets high enough, this extra energy can be enough to overcome the hydrophobic interactions that hold a protein together, causing the protein to unfold. This is what happens when egg whites are cooked: In the uncooked egg whites, albumin is folded, which makes it transparent; cooking them causes the albumin molecules to denature and aggregate, forming a solid, rubbery white mass that will not revert to its transparent form.


Heat denatures proteins for the same reason that raising a reaction's temperature increases its rate: increased average kinetic energy of molecules means increased molecular motion. The relationship between temperature and kinetic energy is discussed in Chapter 7 of MCAT General Chemistry Review.

On the other hand, solutes such as urea denature proteins by directly interfering with the forces that hold the protein together. They can disrupt tertiary and quaternary structures by breaking disulfide bridges, reducing cystine back to two cysteine residues. They can even overcome the hydrogen bonds and other side chain interactions that hold α-helices and β-pleated sheets intact. Similarly, detergents such as SDS (sodium dodecyl sulfate, also called sodium lauryl sulfate) can solubilize proteins, resulting in a hydrophobic core that promotes denaturation of the protein.


Denatured proteins lose their three-dimensional structure and are thus inactive.

MCAT Concept Check 1.6:

Before you move on, assess your understanding of the material with this question.

1.    Why are proteins denatured by heat and solutes, respectively?

·        Heat:

·        Solutes: