ChE 4109 - Enzyme Inhibition

Competitive Inhibition

Inhibitor competes with substrates for binding to active site/binding site.

Competitive Inhibition

Inhibitor is similar in structure to substrate, binds more strongly but reacts more slowly

Competitive Inhibition

Slope is larger compared to normal reaction.

Competitive Inhibition

Type of enzyme inhibition at which the intercept does not change (Vmax)

Competitive Inhibition

Km is larger when compared to normal reaction.

1. Unimolecular Reaction

2. Bimolecular Reaction

Types of competitive inhibition

Uncompetitive Inhibition

Binds only to enzyme-substrate complex but not with free enzyme.

Uncompetitive Inhibition

Binds at location other than active site

Uncompetitive Inhibition

Binding of inhibitor distorts active site thus preventing substrate binding and catalysis

Uncompetitive Inhibition

Cannot be competed away by increasing concentration of substrate as it binds to enzyme only after the substrate has bound.

Uncompetitive Inhibition

Increasing inhibitors lowers Vmax and Km resulting to stronger affinity of the substrate.

Uncompetitive Inhibition

The ratio of Km-to-Vmax (slope) is the same to that of normal reaction.

Noncompetitive Inhibition

The inhibitor does not interfere with substrate binding (and vice versa).

Noncompetitive Inhibition

The inhibitor binds enzyme in its allosteric site irregardless of whether the substrate is bound.

Noncompetitive Inhibition

The inhibitor binds equally well to free enzyme and the enzyme-substrate complex, so it doesn't alter apparent affinity of the enzyme for the substrate.

Noncompetitive Inhibition

In this inhibition, the Vmax decreases proportionately to inhibitor concentration while Km remains unchanged

Noncompetitive Inhibition

Even at high substrate levels inhibitor still binds

Competitive Inhibition

Inhibition is reversible by increasing substrate concentration.

Uncompetitive Inhibition

Substrate binding exposes the inhibitor binding site away from the catalytic/substrate binding site.

Uncompetitive Inhibition/Noncompetitive Inhibition

Increasing substrate concentration does not reverse the inhibition.

Uncompetitive Inhibition

The inhibited reaction rate parallel the normal one as reflected on decreased both Vmax and Km

Noncompetitive Inhibition

The inhibitor binds each of the free enzyme and the substrate-enzyme complex away from the catalytic/substrate binding site.

Irreversible Inhibition

The inhibitor binds to the enzyme irreversibly through formation of a covalent bond with the enzyme, permanently inactivating the enzyme.

Irreversible Inhibition

The inhibitor permanently inactivates the enzyme. The net effect is to remove enzyme from the reaction with Vmax decreasing and Km as equal.

Irreversible Inhibition

This inhibitor covalently modify the enzyme which results in the permanent inhibition of the enzyme activity.

Suicide Inhibitors

Work by "tricking" the enzyme into activating the inhibitor, which then forms a covalent bond with the enzyme, leading to its permanent inactivation.

Penicillin

It is an example of a suicide inhibitor.

Allosteric

It means ”other side”

End Point Inhibition

The end products are controlling their own rate of production

End Point Inhibition

There is no build up of intermediates

Negative Feedback

It is possible during end point inhibition.

Isoenzymes

These are different forms of an enzyme that catalyze the same reaction in different tissues in the body.

Isoenzymes

They have slight variations in the amino acid sequences of the subunits of their quaternary structure.

Lactate dehydrogenase (LDH)

Converts lactate to pyruvate and consists of five isoenzyme

Methanol (CH₃OH)

Metabolized to formaldehyde and formic acid by alcohol dehydrogenase.

Uncompetitive Inhibition

Inhibitor increase the amount of enzyme bound to substrate.