Not every inhibitor blocks the active site
- The idea
- Predict
- See it
- Why
- Check
The idea
“Anything that slows an enzyme down must be blocking its active site.”
Competitive inhibition is usually the first kind you learn, so it's easy to picture every inhibitor plugging the active site. Many bind somewhere else, or never let go.
The short version
The mistake: Anything that slows an enzyme down must be blocking its active site.
What's actually true: Only a competitive inhibitor, which reversibly shares the active site, is overcome by lots of substrate. Others work another way.
- A competitive inhibitor usually looks like the substrate and binds the active site reversibly. Piling on substrate crowds it out, so the rate recovers.
- A noncompetitive inhibitor binds an allosteric site, away from the active site. It reshapes the enzyme so the active site works poorly. Substrate can't push it off.
- An irreversible inhibitor bonds tightly to the enzyme, often covalently. Neither extra substrate nor removing the free inhibitor brings that activity back.
On the exam: Does extra substrate restore the rate? If not, it isn't competitive. It binds elsewhere or won't let go.