Enzymes: Inhibition

Enzymes reaction rates can be decreased by competitive, non-competitive, partially competitive, uncompetitive inhibition, and mixed inhibition.

Competitive inhibition

In competitive inhibition, the inhibitor binds to the substrate binding site as shown (right part b), thus preventing substrate binding. Malonate is a competitive inhibitor of the enzyme succinate dehydrogenase, which catalyzes the oxidation of succinate to fumarate.

Competitive inhibition causes the Km value to increase, but does not effect Vmax.

Non-competitive inhibition

Non-competitive inhibitors never bind to the active center, but to other parts of the enzyme that can be far away from the substrate binding site, consequently, there is no competition between the substrate and inhibitor for the enzyme. The extent of inhibition depends entirely on the inhibitor concentration and will not be affected by the substrate concentration. For example, cyanide combines with the copper prosthetic groups of the enzyme cytochrome c oxidase, thus inhibiting cellular respiration. This type of inhibition is typically irreversible, meaning that the enzyme will no longer function.

By changing the conformation (the three-dimensional structure) of the enzyme, the inhibitors either disable the ability of the enzyme to bind or turn over its substrate. The enzyme-inhibitor (EI) and enzyme-inhibitor-substrate (EIS) complex have no catalytic activity.

Non-Competitive inhibition causes a decrease in Vmax, but does not change the Km value.

Partially competitive inhibition

The mechanism of partially competitive inhibition is similar to that of non-competitive, except that the EIS-complex has catalytic activity, which may be lower or even higher (partially competitive activation) than that of the enzyme-substrate (ES) complex.

This inhibition typically displays a lower Vmax, but an unaffected Km value.

Uncompetitive inhibition

Uncompetitive inhibition occurs when the inhibitor binds only to the enzyme-substrate complex, not to the free enzyme, the EIS complex is catalytically inactive. This mode of inhibition is rare and causes a decrease in both Vmax and the Km value.

Mixed inhibition

Mixed inhibitors can bind to both the enzyme and the ES complex. It has the properties of both competitive and uncompetitive inhibition.

Both a decrease in Vmax and an increase in the Km value are seen in mixed inhibition.


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