INTRODUCTION: VMAX INHIBITOR

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Vmax Inhibitor

There are 4 types of enzymes inhibitor. The Irreversible Inhibition, Competitive Inhibition, Noncompetitive Inhibition and Uncompetitive Inhibition.

Irreversible Inhibition

The enzymes binds the inhibitor, which irreversibly kills it.  Since you destroyed the enzyme successfully, this may cause a decrease in [E]o, resulting in decrease in Vmax, and therefore an apparent decrease in kcat. Attempting to dialyze the inhibitor is not effective  as it is covalently bound to the enzyme. There are many examples of drugs that are irreversible inhibitors.

Competitive Inhibition

In competitive inhibition, the substrate and the inhibitor compete for free enzyme, but each prevent the binding of the other. This implies that they both bind to the active site, which is generally but not always true. By drawing off, in a reversible case, free enzyme from the left of the equilibrium, you are shifting the equilibrium away from ES. This appears to increase the Km. Dialyzing away the inhibitor restores active enzyme (which maybe not true to all reversible models of inhibition.)

Noncompetitive inhibition

In noncompetitive inhibition, substrate binding and inhibitor binding are completely independent of each other, but the ternary complex (ESI) is not productive. The equilibrium between enzyme without substrate and enzyme with substrate is unchanged, but some of each of those happens to have inhibitor. Since the ternary complex can’t make product, this appears the same as removing some enzyme from the pool. This decreases vmax, and therefore apparently decreases kcat. Dialysis restores enzyme activity, as it does for all reversible modes of inhibition. Note that this is the easiest way to determine the difference between this and irreversible inhibition.

Uncompetitive inhibition

This one is a bit odd, in that the inhibitor can only bind to the enzyme- substrate complex, reversibly forming a nonproductive ternary complex.Fitting in with its weird nature, uncompetitive inhibition shifts the equilibrium to the right the same way that competitive inhibition shifts it to the left, apparently *decreasing* the KM (that’s right folks, it looks like it is binding the substrate more tightly). It is also pulling down the pool of enzyme-substrate complex to form the nonproductive ternary complex, decreasing kcat. Carefully study the relationship between this rate equation and those for the other two modes of reversible inhibition shown above, it’s pretty useful. Again, dialysis restores activity. I think this one is kind of nifty.

Mixed inhibition

This one is a pain in the tush. Binding substrate effects the ability of the enzyme to bind substrate, but doesn’t make it zero. Binding inhibitor effects the ability to bind substrate, but doesn’t make it zero. The kcat and KM both apparently change, and your slopes and intercepts are all over the place. It would take a professor significantly more evil than me to make you interpret this one on a test, and that’s saying something...