IGCSE Biology 0610: Optimum pH and Denaturation (Pepsin and Trypsin)

Pepsin is a protease enzyme released in the stomach, where hydrochloric acid keeps the contents strongly acidic at about pH 2. Pepsin's optimum pH is about pH 2. Trypsin is a different protease enzyme, released into the small intestine, where the contents are slightly alkaline at about pH 8 because acid from the stomach has been neutralised. Trypsin's optimum pH is about pH 8.

(a) Explain why pepsin can digest protein efficiently in the stomach, while trypsin cannot function well there. [2]

(b) Trypsin is accidentally exposed to the strongly acidic conditions of the stomach (pH 2) for a long period of time. In terms of the bonds that hold an enzyme's three-dimensional shape together, explain what happens to trypsin's active site, and why this change cannot be reversed simply by moving the trypsin into the less acidic conditions of the small intestine. [3]

(c) Suggest one advantage to the body of pepsin having an optimum pH that matches the stomach, rather than sharing the same optimum pH as trypsin. [1]

Part (a): Why pepsin, not trypsin, works well in the stomach

Each enzyme has an optimum pH, the pH at which its active site has exactly the right shape to bind its substrate. Pepsin’s optimum pH of about 2 matches the naturally acidic stomach, so pepsin’s active site keeps its correct, complementary shape there, allowing protein substrate to bind and form enzyme-substrate complexes efficiently.

Trypsin’s optimum pH is about 8. Stomach pH 2 is a long way from this optimum, so trypsin’s active site is not in its correct shape in the stomach, and it cannot bind protein substrate effectively, trypsin therefore cannot function well in the stomach.

Part (b): The molecular effect of extreme pH on trypsin

A protein’s three-dimensional shape, including the shape of an enzyme’s active site, is held together partly by bonds between different parts of the folded amino acid chain, such as hydrogen bonds and ionic bonds. Exposing trypsin to pH 2, far from its optimum of pH 8, disrupts these bonds.

Once these bonds are broken, the folded shape of trypsin, including its active site, is permanently changed: trypsin is denatured, and its active site is no longer complementary to its substrate, so no more enzyme-substrate complexes can form.

Because the original bonds have been broken and the protein chain has settled into a different, disorganised shape, simply moving the trypsin into the small intestine’s more suitable pH 8 does not automatically re-form the original bonds or restore the original active site shape. The change is permanent, so trypsin remains unable to function even once it reaches its normal environment.

Part (c): The advantage of matched optimum pH values

If pepsin and trypsin shared the same optimum pH, one of them would always be working far from its ideal conditions in its own part of the gut. By having an optimum pH that matches the strongly acidic stomach, pepsin can begin breaking down dietary protein efficiently as soon as food arrives there, rather than protein passing through largely undigested until it reaches the small intestine, where trypsin, with its own matched optimum pH of about 8, then continues the digestion.

Final answers

(a) Pepsin’s optimum pH (about 2) matches the stomach, so its active site works there; trypsin’s optimum pH (about 8) does not match the stomach, so its active site is the wrong shape there.
(b) The extreme acidity breaks bonds (e.g. hydrogen and ionic bonds) holding trypsin’s three-dimensional shape together, permanently changing its active site’s shape (denaturing it); this cannot be reversed by simply restoring a more suitable pH.
(c) It allows protein digestion to begin efficiently in the stomach itself, immediately at the point where the strongly acidic conditions naturally occur.