Competitive reversible inhibition: raised apparent Km, unchanged Vmax
A competitive reversible inhibitor (it comes off again) competes for the active site, raising the apparent Km (substrate concentration giving half of Vmax, the maximal rate) while Vmax is unchanged.
Remember
A competitive reversible inhibitor raises the apparent Km but leaves Vmax unchanged, because enough substrate overcomes it. If Vmax stays low however much substrate is added, the inhibitor is not competitive.
Memory aid
Picture competitors taking some of the seats in a theatre: a big enough crowd of substrate still fills them all, so Km goes up and Vmax stays the same.
The inhibitor takes some of the seats, but a big enough crowd of substrate still fills them all.
An enzyme's active site is the pocket where the substrate binds and the reaction takes place. A competitive inhibitor has a shape similar to the substrate, so it can sit in that pocket and block the substrate from getting in. The two molecules compete for the same site.
The binding is reversible. The inhibitor attaches by weak, non-covalent bonds, which are not permanent chemical links, so it can come off again. Because the contest depends on the relative amounts of substrate and inhibitor, adding much more substrate means the substrate wins most contests. The enzyme can then still reach its normal top speed, so Vmax (the maximal rate, reached when every active site is occupied by substrate) is unchanged.
At lower substrate concentrations, though, the inhibitor blocks a share of the active sites. More substrate is therefore needed to reach half of Vmax, and Km, the substrate concentration that gives half of Vmax, goes up. This raised Km is called the apparent Km because the enzyme itself has not changed. It simply behaves as if it grips the substrate less tightly, which means a lower apparent affinity (how readily the enzyme grips its substrate).
On a graph of rate against substrate concentration, the curve shifts to the right but still levels off at the same plateau, the Vmax.
By contrast, a non-competitive inhibitor binds an allosteric site (a site other than the active site), so Vmax falls and, in the pure form, Km is unaffected. Extra substrate does not restore the rate. Uncompetitive inhibition (the inhibitor binds only after the substrate is already attached) lowers both Km and Vmax, and an irreversible inhibitor permanently inactivates enzyme molecules.
Key facts
- Where it binds
- the active site, through non-covalent bonds, so it competes with the substrate.
- Effect on Km
- the apparent Km increases, so the enzyme appears to have a lower affinity for its substrate.
- Effect on Vmax
- unchanged, because adding enough substrate overcomes the inhibitor.
- Rate curve
- shifts to the right but approaches the same plateau.
- Rescue by substrate
- a useful rule is to ask whether more substrate restores the maximum rate; if it does, the inhibitor is competitive.
Exam traps
- A lower Km does not fit competitive inhibition, because it would mean a higher affinity, whereas a competitive inhibitor makes it harder for the substrate to reach the active site.
- An unchanged Km with a reduced Vmax is the pattern of pure non-competitive inhibition, not competitive, because the inhibitor binds away from the active site and extra substrate does not restore the rate.
- A competitive inhibitor does bind the active site, but it does not lower the maximum rate, because enough substrate can overcome its effect.
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