1.3 Inhibition

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

1.3.1 Competitive inhibition

The inhibitor may bind to the substrate binding site as shown in the figure, thus preventing substrate binding. Alternatively, binding of substrate to a different binding site may change protein conformation in a way that prevents substrate binding, while substrate binding changes protein conformation to prevent inhibitor binding. These two possibilities can not be distinguished by enzyme kinetics (X-ray crystallography would be a suitable method), thus the frequently found statement that competitive kinetics proves inhibitor binding at the substrate site is false.

1.3.2 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.

1.3.3 Non-competitive inhibition

Non-competitive inhibitors (I) never bind to the active center, but to other parts of the enzyme (E) that can be far away from the substrate (S) binding site. By changing the conformation (the three-dimensional structure) of the enzyme (E), they disable or enable the ability of the enzyme (E) to turn over its substrate (S), while substrate binding is still possible (in other words: there is no competition between substrate and inhibitor for the enzyme). The EIS-complex has no catalytic activity.

1.3.4 Partially competitive inhibition

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

2 Enzyme inactivation

Inactivators bind to the enzyme irreversibly (while binding of inhibitors is per definitionem reversible). Of particular medical importance are suicide inactivators which bind to the enzyme at a substrate binding site and are then turned over into a compound and do not release the site, preventing the substrate from binding. Certain irreversible neurotoxins, for example, have this property, while other, reversible, toxins do not.

3 Kinetics

Enzyme kinetics is referred to as Henri-Michaelis-Menten kinetics. The Michaelis constant, and the Lineweaver-Burke diagram help to define enzyme kinetics.

Enzymes

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