2. Kinetics

Enzyme Inhibition, Part 2

The second type of inhibitor is an uncompetitive inhibitor. These inhibitors can only bind the enzyme when the enzyme associated with a substrate, ES. This complex becomes unproductive—can’t produce product. Intuitively, Vmax will lower because a portion of the ES will become trapped in the unproductive ESI complex.

Now, adding an inhibitor, the [ES] will decrease because of the formation of ESI. But this will shift the equilibrium of the reaction to the right (by Le Chatelier’s Principle), meaning the [ES] will start to increase and thus [E][S]/[ES] will decrease => Km will be smaller.

A revised Lineweaver-Burke Equation for uncompetitive inhibitors:

1/V0 = (Km/Vmax)(1/[S] ) + α’/Vmax

α’ = 1 + [I]/ K’i

The slopes of with and without the uncompetitive inhibitor are the same. But the y-intercept is higher, which means that 1/Vmax is higher and thus Vmax is smaller, consistent with intuition. Similarly, it can be shown that Km is smaller too.

The third type of inhibitor is the mixed inhibitor. These inhibitors bind to both the E and the ES. Because it has uncompetitive behavior, it impedes the formation of product and thus lowers the Vmax. The behavior of Km is more complicated.

1/V0 = (αKm/Vmax)(1/[S] ) + α’/Vmax

While the y-intercept will always be higher, the x-intercept will vary based on the formation rates of EI and ESI. So, Km can larger, smaller, or equal.

There are also irreversible inhibitors, such as the “suicide inhibitors” used in medicine. Not discussed here.


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