Lecture test 2 Q2d: How pH changes affect enzymatic reaction

I have finished marking the lecture tests and I wish to highlight one question that was very poorly attempted in the test here. Although most of you are already aware that a change in pH from the optimum (more than or less than optimum) decreases enzyme activity, alot of you were unable to explain the mechanism behind this effect. Actually, the mechanism is already spelt out very clearly in your lecture notes so please go over it again to make sure you are clear about what I am saying here.

I also want to clarify some terms here as some of you seem to be confused over these terms. The enzyme is a globular protein that has undergone FOLDING to achieve its respective secondary/tertiary/quaternary (if more than one polypeptide chain) structures. Hence it has a specific CONFORMATION/configuration/3D structure as a result of the folding. And it is due to this conformation that the enzyme has a specific SHAPE in its ACTIVE SITE, which is complementary to the shape of its substrate. To summarise, "conformation" is not the same as "shape" so please don't use them interchangeably. The enzyme has a specific "conformation" while the active site has a specific "shape". Hope that this is clear.

Now let's move on to the mechanism. As I have already mentioned in class,  a change in pH changes the concentration of H+ and OH- ions, which causes the neutralisation of polar/charged R groups in the enzyme.

But what you should also know is that this effect can occur at the follwoing 2 areas of the enzyme. 

(i) At the active site -

At the active site, the catalytic and contact residues have charged R groups.

Hence, NEUTRALISATION of these CHARGED R groups disrupts the formation of INTERmolecular IONIC AND HYDROGEN bonds between the active site on the ENZYME and the SUBSTRATE. 

(ii) At other regions of the enzyme -

The bulk of the globular structure of the enzyme contain polar R groups (that form hydrogen bonds) and charged R groups (that form ionic bonds), which stabilise/maintain the secondary, tertiary and/or quaternary structures of the enzyme.

Hence, NEUTRALISATION of these POLAR/CHARGED R groups disrupts the INTRAmolecular IONIC AND HYDROGEN bonds maintaining the SECONDARY, TERTIARY and/or QUATERNARY structure of the enzyme. This causes the enzyme to unfold and lose its specific conformation (ie. denaturation) of the enzyme, hence causing the active site to lose its specific shape.

With both disruptions, binding of the substrate to the active site of the enzyme to form enzyme-substrate complexes, and hence products are prevented. And that is why the enzymatic activity decreases!