noncompetitive inhibition

Meaning: The inhibitor binds an allosteric site, not the active site, and in the pure case binds free enzyme and the enzyme–substrate complex with equal affinity. Substrate binding is unaffected, so Km stays the same, but less enzyme is functional, so Vmax falls. Extra substrate cannot overcome it.

Equation: v = Vmax[S] / ((Km + [S])(1 + [I]/Ki)). Here v and Vmax are rates (mol/(L·s)); [S] and [I] are substrate and inhibitor concentrations (mol/L); Km is the Michaelis constant (mol/L); Ki is the inhibitor dissociation constant (mol/L).

On the MCAT: Passages show Michaelis–Menten or Lineweaver–Burk plots with and without inhibitor. Pure noncompetitive inhibition gives a lower plateau with the same Km. On the double-reciprocal plot the lines cross on the x-axis at −1/Km, and the inhibited line has a larger y-intercept (1/Vmax). Expect questions on whether raising [S] restores activity (it does not).

Common confusion: Competitive inhibition raises Km, leaves Vmax unchanged, is overcome by substrate, and gives lines that cross on the y-axis. Uncompetitive inhibition binds only the enzyme–substrate complex and lowers both Vmax and Km (parallel lines). In mixed inhibition the affinities for E and ES differ, so Km also shifts; some texts loosely call this noncompetitive.