The value of Ki calculated for competative and non competitive enzyme inhibitors. Normally I have got maximum activity for 'a' compound, means it has got least IC50 value. It followed non- competitive inhibition. But on finding Ki value, I have got least Ki for compound 'b' which followed competitive inhibition. Why this happens? Is there any discrepancy regarding this?
Is this the situation?
You have 2 compounds, A and B, which inhibit some enzyme.
A is a noncompetitive inhibitor.
B is a competitive inhibitor.
The IC50 of A is lower than the IC50 of B.
The Ki of B is lower than the Ki of A.
The IC50 of a pure noncompetitive inhibitor is equal to its Ki.
The IC50 of a pure competitive inhibitor is higher than its Ki because of the presence of the substrate with which it competes. The relationship between the IC50 and Ki of a competitive inhibitor for a single-substrate enzyme is
IC50 = Ki(1 + [S]/Km). For multiple-substrate enzymes, a more complicated equation applies (see Cheng-Prusoff relationship). Depending on the substrate concentration [S], the IC50 can have any value above the Ki.
Given that the Ki of B is lower than that of A, it is possible for the IC50 of B to be higher than the IC50 of A because of competition with the substrate.
If the inhibition is competitive, an IC50 is useless because the value determined experimentally will depend on the substate concentration used in the assay. In general it is better to use Ki values for comparing the potency of inhibitors instead of IC50 unless it has been established that the inhibition is noncompetitive.
Peter
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