enzyme inhibition

Meaning: Enzyme inhibition is a decrease in an enzyme's rate caused by an inhibitor. Reversible inhibitors bind noncovalently; irreversible ones usually bind covalently. Competitive: binds the active site, raising apparent Km while Vmax stays the same. Noncompetitive: binds a site other than the active site on E and ES equally, lowering Vmax with Km unchanged. Uncompetitive: binds only the ES complex, lowering both Vmax and Km. Mixed: binds E and ES with different affinities, lowering Vmax with Km shifting up or down.

Equation: v = Vmax[S] / (αKm + [S]), where α = 1 + [I]/Ki (competitive case). v is reaction rate and Vmax is maximum rate (both in M/s); [S] and [I] are substrate and inhibitor concentrations, and Km and Ki are the Michaelis and inhibitor dissociation constants (all in M); α is dimensionless.

On the MCAT: Passages show a Lineweaver-Burk plot (1/v against 1/[S]) with and without inhibitor. Lines meeting on the y-axis indicate competitive inhibition, lines meeting on the x-axis indicate pure noncompetitive inhibition, and parallel lines indicate uncompetitive inhibition.

Common confusion: Students think extra substrate defeats any inhibitor. It overcomes only competitive inhibition, because enough substrate outcompetes the inhibitor and Vmax is still reached. Noncompetitive inhibition lowers Vmax however much substrate is added.