Reversible noncompetitive inhibition

A noncompetitive inhibitor binds reversibly at a site other than the active site and  causes  a  modification  in  the  whole  3D  shape  of  the enzyme which leads to a decrease in catalytic activity. Because the inhibitor binds at a various site from the substrate the enzyme should bind the inhibitor,   the substrate or both the substrate and inhibitor together. The effects of a noncompetitive inhibitor cannot be overcome through increasing the substrate concentration so there is a reduction in V_max.  In noncompetitive  inhibition  the affinity  of the  enzyme  for  the  substrate  is not changed  and  so K_m   remains  the similar. An instance of noncompetitive inhibition is the action of pepstatin on the enzyme renin.

Noncompetitive   inhibition  can  be  known  on  a  Lineweaver–Burk  plot because it increase  the slope of the experimental  line and alters the intercept  on the  y-axis  because  V_max is  decreased   but  leaves  the  intercept   on  the  x-axis unchanged because K_m  remains constant.

                                        Figure  Inhibition of succinate dehydrogenase by malonate

Figure: The characteristics of noncompetitive inhibition. (a) A noncompetitive inhibitor binds at a site distinct from the active site; (b) the enzyme can bind either substrate or the noncompetitive inhibitor or both; (c) Lineweaver-Burk plot showing the effect of a noncompetitive inhibitor on K_m  and V_max.