What a competitive inhibitor really does to Km

Two inhibitors, two different lies your intuition tells you. The Michaelis-Menten curve settles the argument.

hard
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A competitive inhibitor is in the tube. What happens to Vmax and Km?

Vmax unchanged. Km rises.

⚠ Trap

That can't be right. If something blocks the active site, the top speed has to drop.

That's the intuition the exam preys on. A competitive inhibitor only sits where substrate would.

So?

Flood the tube with enough substrate and it outcompetes the inhibitor at every site.

And the enzyme reaches?

Its original Vmax. It just takes more substrate to get there.

Which is what Km measures.

Right. A higher apparent Km. That's the whole signature.

Define Km for me, since it all hinges on it.

The substrate concentration at which velocity is half of Vmax.

So it's a speed?

No, and that's the second trap. It's a concentration. An inverse proxy for affinity.

Low Km means?

Tight binding. The enzyme hits half-speed with very little substrate.

Now swap in a pure noncompetitive inhibitor. Same two questions.

Mirror image. Vmax falls. Km unchanged.

Why the flip?

It binds an allosteric site, substrate or no substrate. You can't out-add it.

So fewer working enzymes.

A lower ceiling. But the ones still working bind substrate exactly as before.

I hand you a Lineweaver-Burk plot, no labels. How do you tell them apart?

Look at the intercepts.

What am I looking for?

Competitive shares the y-intercept, same 1 over Vmax, steeper slope. Noncompetitive shares the x-intercept, same minus 1 over Km.

The one-line takeaway?

The point the lines pivot around tells you which quantity was spared.

↑ answer it in your head first ↑

the mistakes this catches

Traps

  • Thinking a competitive inhibitor lowers Vmax. It doesn't, enough substrate outcompetes it and Vmax is restored.
  • Reading Km as "how fast the enzyme goes." Km is a substrate concentration, an inverse proxy for affinity.
  • Assuming all inhibitors can be overcome by adding substrate. Only competitive inhibition is surmountable that way.
test yourself, tap to flip

Flash drills

1 What does Km represent? tap →
The substrate concentration at which reaction velocity is half of Vmax. A low Km means high apparent affinity, the enzyme reaches half-speed with little substrate.
2 How does a competitive inhibitor change Km and Vmax? tap →
It raises the apparent Km (more substrate needed to reach half-speed) and leaves Vmax unchanged, because excess substrate outcompetes the inhibitor at the active site.
3 How does a pure noncompetitive inhibitor change Km and Vmax? tap →
It lowers Vmax and leaves Km unchanged. It binds an allosteric site regardless of substrate, so adding substrate cannot overcome it.
4 On a Lineweaver-Burk plot, how do you tell them apart? tap →
Competitive inhibition shares the same y-intercept (1/Vmax) with a steeper slope; noncompetitive inhibition shares the same x-intercept (−1/Km) with a higher y-intercept.
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