Biochemistry · Enzyme kinetics
Competitive vs noncompetitive inhibition
Reversible inhibitors are told apart by what they do to apparent Km and Vmax. A Lineweaver-Burk plot shows each pattern as a different way the lines cross.
Summary table
| Type | Binds | Apparent Km | Apparent Vmax | Lineweaver-Burk lines |
|---|---|---|---|---|
| Competitive | Free enzyme (active site) | Increases | Unchanged | Cross on the y-axis |
| Uncompetitive | Enzyme-substrate complex only | Decreases | Decreases (same factor) | Parallel |
| Noncompetitive (pure) | E and ES equally | Unchanged | Decreases | Cross on the x-axis |
| Mixed | E and ES unequally | Increases or decreases | Decreases | Cross off both axes |
Why the patterns happen
A competitive inhibitor can be outcompeted: enough substrate still reaches the full Vmax, but more is needed to get there, so Km rises. For competitive inhibition, apparent Km = α Km, where α = 1 + [I]/Ki.
Inhibitors that bind the enzyme-substrate complex remove active enzyme no matter how much substrate is added, so Vmax falls.
Practice problems
1. A competitive inhibitor is present at a concentration equal to its Ki. What happens to apparent Km?
Show answer
α = 1 + 1 = 2, so apparent Km doubles. Vmax does not change.
2. With an inhibitor, the Lineweaver-Burk line is parallel to the uninhibited line but shifted up. What type is it?
Show answer
Uncompetitive. Slope (Km/Vmax) is unchanged because both drop by the same factor.
3. Adding a lot more substrate restores full activity. Which type of inhibitor is most likely?
Show answer
Competitive, because high [S] outcompetes it.
Frequently asked questions
Is noncompetitive the same as mixed inhibition?
Pure noncompetitive inhibition is the special case of mixed inhibition where the inhibitor binds E and ES equally, so Km stays the same.
Does an irreversible inhibitor fit these patterns?
No. Irreversible inhibitors remove active enzyme, lowering Vmax, and are not described by an equilibrium Ki.
Reference: Berg et al., Biochemistry, chapter 8; Nelson and Cox, Lehninger Principles of Biochemistry, chapter 6.