Competitive vs Non-Competitive Inhibitors
How competitive and non-competitive inhibitors slow an enzyme-controlled reaction, where each binds, and what raising substrate concentration does in each case. Includes the 4-mark exam question, a worked model answer and the examiner trap on saying where the inhibitor binds.
Chapters (9)
Exam question [4 marks]
Inhibitor A and inhibitor B both slow the same enzyme-controlled reaction. A is a competitive inhibitor and B is a non-competitive inhibitor. Explain how each inhibitor reduces the rate, and why increasing substrate concentration affects them differently.
Try it on paper first, then check the mark scheme below. The question is original and was written for this lesson.
Mark scheme
| Mark | Mark point | Also accept | Do not accept |
|---|---|---|---|
| 1 | Competitive inhibitor has a shape similar to the substrate and binds to the active site, so fewer enzyme-substrate complexes form | "complementary to the active site", "blocks the active site", "competes with substrate for active site" | "binds to the enzyme" with no site stated; "same shape as the enzyme" |
| 2 | Increasing substrate concentration makes substrate more likely to bind than the inhibitor, so rate increases (towards the maximum rate) | "substrate outcompetes inhibitor", "higher substrate to inhibitor ratio", "more enzyme-substrate complexes" | "more substrate removes the inhibitor"; "more substrate speeds up rate" with no reference to competition |
| 3 | Non-competitive inhibitor binds to a different site (allosteric site), changing the tertiary structure so the shape of the active site changes and substrate can no longer bind | "binds away from the active site", "active site no longer complementary" | "binds to the enzyme" alone; "changes the shape of the enzyme" with no mention of the active site |
| 4 | Increasing substrate concentration does not overcome this, because fewer functional enzyme molecules are available, so the maximum rate is lower | "inhibitor not competing for active site", "rate still levels off at a lower level", "all non-inhibited enzymes working at maximum rate" | "substrate cannot reach the active site"; "enzymes run out of substrate" |
Marks 1 and 2 are for the competitive inhibitor, 3 and 4 for the non-competitive. The commonest lost mark is the site: "binds to the enzyme" scores nothing. For mark 3 the change in shape of the active site must be stated, not just a change to the enzyme. Adding more inhibitor lowering the rate further is creditable but does not add marks beyond 4.
Model answer (4/4)
Inhibitor A has a shape similar to the substrate, so it binds to the active site and fewer enzyme-substrate complexes form. Increasing the substrate concentration makes the substrate more likely to bind than the inhibitor, so the rate increases again. Inhibitor B binds to a different site on the enzyme, which changes the tertiary structure, so the shape of the active site changes and the substrate can no longer bind. Increasing the substrate concentration does not overcome this, because fewer functional enzymes are available, so the maximum rate stays lower.
Examiner trap
- Saying competitive inhibitors 'bind to the enzyme' without saying active site
- Saying that raising substrate concentration overcomes non-competitive inhibition
- Not saying non-competitive binding changes the shape of the active site
Key terms
- competitive inhibitor
- non-competitive inhibitor
- active site
- allosteric site
- tertiary structure
- substrate concentration
- enzyme-substrate complex
Lesson notes
A written version of the video, chapter by chapter, for revision. Times link to the video.
0:25Quick reset: the active site
Quick reset. An enzyme has an active site, with a tertiary structure that is complementary to its substrate. The substrate fits in, an enzyme-substrate complex forms, and the product is released. An inhibitor is anything that reduces the rate of that reaction by blocking the reaction. There are two types, and they block it in completely different places.
0:49Competitive inhibitor
First, the competitive inhibitor. It has a shape similar to the substrate. So it fits into the active site. While it sits there, the substrate cannot get in, so fewer enzyme-substrate complexes form, and the rate falls.
It competes with the substrate for the same active site.
1:07More substrate: competitive
Now, what happens if we add more substrate? The substrate molecules start to outnumber the inhibitor, so they bind to the active sites more often. This is why the rate climbs again, and the curve can reach the same maximum rate as without the inhibitor. So with a competitive inhibitor, more substrate overcomes the inhibition.
Notice the key idea. The effect depends on the ratio of substrate to inhibitor. Swamp the inhibitor, and it stops mattering.
1:38Non-competitive inhibitor
Next, the non-competitive inhibitor. This one does not go in the active site at all. It binds to a different place on the enzyme, called an allosteric site. And that matters, because binding there changes the tertiary structure of the enzyme.
So the shape of the active site changes. The substrate is no longer complementary, so it cannot bind, and fewer enzyme-substrate complexes form.
Notice, the inhibitor and the substrate are not fighting over the same spot.
2:10More substrate: non-competitive
So what happens when we add more substrate here? The rate still rises, but only up to a lower maximum rate. Some enzymes are out of action, however much substrate there is. So the rate levels off early, at that lower maximum. More substrate does not overcome non-competitive inhibition.
The inhibitor is not competing for the active site, so a higher concentration of substrate cannot push it out.
At a given substrate concentration, adding more inhibitor, in either case, lowers the rate further, because more enzymes are affected.
2:45Side by side
Let's put them side by side. Competitive binds at the active site. Non-competitive binds at another site. Competitive leaves the shape of the active site alone. Non-competitive changes it. And more substrate overcomes the first, but not the second.
3:49Examiner trap and recap
The trap. Saying an inhibitor binds to the enzyme is not enough. Say where. Competitive, the active site. Non-competitive, a different site, which changes the shape of the active site.
Recap. Competitive competes for the active site, and more substrate beats it. Non-competitive changes the active site, and more substrate does not help.
Next up, a required practical. How do you actually investigate the rate of an enzyme-controlled reaction?
Watch first
This lesson builds on:
- How Enzymes Work: Active Site and Induced Fit · AQA 7402 · 3.1.4.2
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