noncompetitive

Meaning: A noncompetitive inhibitor binds an allosteric site, not the active site, on either the free enzyme or the enzyme–substrate complex. It does not block substrate binding, but enzyme with inhibitor bound cannot catalyze. The pool of working enzyme shrinks, so Vmax falls. In the pure case the inhibitor binds E and ES equally well, so substrate affinity is unchanged and Km stays the same. Extra substrate cannot overcome it.

Equation: Vmax(app) = Vmax / (1 + [I]/Ki), with Km unchanged. Vmax(app) and Vmax are rates in mol/(L·s); [I] is inhibitor concentration and Ki the inhibitor dissociation constant, both in mol/L.

On the MCAT: On a Michaelis–Menten plot, the inhibited curve plateaus lower but reaches half its maximum at the same [S]. On a Lineweaver–Burk plot, the lines cross on the x-axis at −1/Km, and the inhibited line has a higher y-intercept (1/Vmax) and a steeper slope.

Common confusion: Competitive inhibition raises Km with Vmax unchanged. Uncompetitive inhibition binds only ES and lowers both Vmax and Km (parallel lines). If the inhibitor binds E and ES with unequal affinity, it is mixed inhibition and Km shifts, though some texts still call this noncompetitive. Pure noncompetitive means Vmax down, Km same.