The highly organized structures of proteins are truly masterworks of chemical architecture. But highly organized structures tend to have a certain delicacy, and this is true of proteins. Denaturation is the term used for any change in the three-dimensional structure of a protein that renders it incapable of performing its assigned function. A denatured protein cannot do its job. A wide variety of substances and conditions, such as heat, organic compounds, pH changes, and heavy metal ions can cause protein denaturation.

Anyone who has fried an egg has observed denaturation. The clear egg white turns opaque as the albumin denatures and coagulates. No one has yet reversed that process. However, given the proper circumstances and enough time, a protein that has unfolded under sufficiently gentle conditions can refold and may again exhibit biological activity. Such evidence suggests that, at least for these proteins, the primary structure determines the secondary and tertiary structure. A given sequence of amino acids seems to adopt its particular three-dimensional arrangement naturally if conditions are right.

A protein is shown folded up into its correct 3D shape. Then after denaturation, the protein is unraveled and becomes an expanded chain. After renaturation, the protein remolds to its correct 3D shape.
Denaturation and Renaturation of a Protein. The denaturation (unfolding) and renaturation (refolding) of a protein is depicted. The red boxes represent stabilizing interactions, such as disulfide linkages, hydrogen bonding, and/or ionic bonds.

Denaturation does not affect the primary structure of proteins. Fairly vigorous conditions are needed to hydrolyze the peptide bonds of the primary structure. At the secondary through quaternary levels, however, proteins are quite vulnerable to attack, though they vary in their vulnerability to denaturation. The delicately folded globular proteins are much easier to denature than are the tough, fibrous proteins of hair and skin.

Concept Review Exercises

  1. Briefly describe four ways in which a protein could be denatured.
  2. What level(s) of protein structure is(are) ordinarily disrupted in denaturation? What level(s) is(are) not?


  1. (1) heat a protein above 50°C or expose it to UV radiation; (2) add organic solvents, such as ethyl alcohol, to a protein solution; (3) add salts of heavy metal ions, such as mercury, silver, or lead; and (4) add alkaloid reagents such as tannic acid
  2. Protein denaturation disrupts the secondary, tertiary, and quaternary levels of structure. Only primary structure is unaffected by denaturation.


This page is based on “Chemistry 2e” by Paul Flowers, Klaus Theopold, Richard Langley, William R. Robinson, PhDOpenstax which is licensed under CC BY 4.0. Access for free at

This page is based on “The Basics of General, Organic, and Biological Chemistry” by David W Ball, John W Hill, Rhonda J ScottSaylor which is licensed under CC BY-NC-SA 4.0. Access for free at


Icon for the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License

Chemistry of Food and Cooking Copyright © 2022 by Jessica Wittman is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.