Pure vs Mixed Noncompetitive Inhibition: Km, Vmax and Lineweaver-Burk

Noncompetitive inhibitors bind away from the active site, so they can bind the free enzyme (E) or the enzyme-substrate complex (ES). Pure and mixed differ in whether the inhibitor binds E and ES equally well.

Comparison

The Vmax drop happens in both because some enzyme is effectively removed from catalysis, and adding substrate does not rescue it.

Why Km differs

• Pure: the inhibitor binds E and ES equally, so it does not change how well substrate binds. Km is unchanged.
• Mixed, prefers E: substrate binding is hindered, so apparent Km increases.
• Mixed, prefers ES: substrate binding is favored, so apparent Km decreases.

Many textbooks and the MCAT use "noncompetitive" for the pure case. Mixed inhibition is a general case; competitive and uncompetitive are its limiting forms.

Compared with other types

• Competitive: binds E only. Km up, Vmax unchanged, lines meet on the y-axis.
• Uncompetitive: binds ES only. Km and Vmax both down, parallel lines.

Common traps

• Thinking more substrate overcomes noncompetitive inhibition. It does not.
• Saying Km changes in pure noncompetitive inhibition.
• Forgetting that Lineweaver-Burk uses reciprocals. The x-intercept is -1/Km.

One-minute recap

• Pure: Vmax down, Km same.
• Mixed: Vmax down, Km shifts either way.
• Both bind away from the active site.