Noncompetitive inhibition

This type of inhibition is recognized by its characteristic effect on V_max (Fig. 1). Noncompetitive inhibition occurs when the inhibitor and substrate bind at different sites on the enzyme. The noncompetitive inhibitor can bind either free enzyme or the enzyme–substrate complex, thereby preventing the reaction from occurring (Fig. 2).

Figure 1:  A. Effect of a noncompetitive inhibitor on the reaction velocity versus substrate concentration ([S]) plot. B. Lineweaver-Burk plot of noncompetitive inhibition of an enzyme. [Note: The slope increases if inhibitor concentration increases.]

Figure 2:  A noncompetitive inhibitor binding to both free enzyme and enzyme–substrate (ES) complex.
1. Effect on V_max: Noncompetitive inhibition cannot be overcome by increasing the concentration of substrate. Therefore, noncompetitive inhibitors decrease the apparent Vmax of the reaction.
2. Effect on K_m: Noncompetitive inhibitors do not interfere with the binding of substrate to enzyme. Therefore, the enzyme shows the same K_m in the presence or absence of the noncompetitive inhibitor, that is, K_m is unchanged.
3. Effect on Lineweaver-Burk plot: Noncompetitive inhibition is readily differentiated from competitive inhibition by plotting 1/vo versus 1/[S] and noting that the apparent Vmax decreases in the presence of a noncompetitive inhibitor, whereas Km is unchanged (see Fig. 1).
[Note: Oxypurinol, a metabolite of the prodrug allopurinol, is a noncompetitive inhibitor of xanthine oxidase, an enzyme of purine degradation ]