Non-competitive Inhibition

A non-competitive inhibitor does not bind to the active site. Instead it binds to another part of the enzyme, called an allosteric site. Its shape does not need to resemble the substrate.When the inhibitor binds, it changes the enzyme's tertiary structure. This alters the shape of the active site, so the substrate can no longer bind (or the reaction can no longer be catalysed). Fewer enzyme-substrate complexes form and the rate falls.Because the inhibitor and substrate are not competing for the same site, increasing the substrate concentration cannot overcome the inhibition. Every enzyme molecule with inhibitor bound is effectively out of action, whatever the substrate concentration. So the maximum rate (V_max) is lowered, and the curve levels off at a lower value.The degree of inhibition depends on the inhibitor concentration: more inhibitor inactivates more enzyme molecules. Non-competitive inhibitors can be reversible or irreversible.Comparing the two types:
• competitive: binds active site, similar shape to substrate, overcome by more substrate, V_max unchanged
• non-competitive: binds allosteric site, shape unlike substrate, not overcome by more substrate, V_max reducedWorked example: with a non-competitive inhibitor present, the maximum rate falls from 10 to 6 units. Activity is reduced by (10 − 6) ÷ 10 × 100 = 40%.