An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. This union can be reversible, the most common in the case of drugs, or irreversible, which is usually due to xenobiotics with a high toxic capacity, such as many pesticides and high reactivity chemicals.
In practice, the inhibition will lead to a slower metabolism of the affected active ingredients,which will result in higher plasma concentrations if they are drugs (it will produce of overdose effect) or lower effective plasma concentrations, if the active ingredient affected is a pro-drug (less drug transformation and risk of disorders due to an ineffective dose).
There are three types of reversible inhibitors. They are classified based on the effect produced by the inhibitor on the variation of the concentration of the substrate in the enzyme.
Competitive inhibition. Two (or more) substrates can not be linked at the same time to the active center of the same enzyme of which both (or all of them) are substrates. Therefore they will “bother” each other and “compete” to join the active center. The union should be done in an alternative way and the substrate that is in higher concentration will be more likely to join than the one that is in lower concentration. This may also happen with other substances with affinity for the active site of an enzyme which also binds the substrate; the substrate and the inhibitor “compete” for access to the active site of the enzyme. This type of inhibition, “in vitro” can be overcome with sufficiently high concentrations of the substrate, that is, leaving the inhibitor out of competition, now “in vivo” and specifically in therapy, it is not usually possible because it would increase the dose of the drug, which could cause undesirable effects due to overdose. Competitive inhibitors are often similar in structure to the true substrate.
Mixed inhibition. In this case the inhibitor can bind to the enzyme at the same time as the substrate. However, the inhibitor ‘s binding affects the substrate, and vice versa. This type of inhibition can be reduced, but not overcome, by increasing substrate concentrations. Although it is possible that the mixed-type inhibitors bind in the active site, such inhibition generally results from an allosteric effect by the inhibitor binds to another site that is not the active site of the enzyme. The binding of the inhibitor to the allosteric site of the conformation, the tertiary structure of the enzyme, means that modifying the structure, the substrate affinity for the active site is reduced.
Non-competitive inhibition. It is produced because the inhibitor binds to the enzyme in a way that does not affect the configuration of the active center, so that can be attached without problems with the substrate, but significantly affect its activity. As a result, the degree of inhibition depends only on the inhibitor concentration.
Irreversible inhibition. Irreversible inhibitors usually an enzyme modified by covalent bonds with such amino acid residues of the molecule, especially cysteine (-SH group), threonine, serine, tyrosine (all -OH groups), which inhibition cannot be reversed. These inhibitors are usually molecules of the type of pesticides and other highly reactive chemical agents, being more important in the field of chemical and environmental toxicology than pharmacology.
Dr. Juan Sabater-TobellaEuropean Specialist in Clinical Chemistry and Laboratory Medicine (EC4)Member of the Pharmacogenomics Research NetworkMember of the International Society of Pharmacogenomics and Outcomes ResearchPresidente de EUGENOMIC®
This text has been translated automatically using an electronic translator, so the Spanish version should prevail. Please check in case of doubt.
Last modified: Mar 14, 2018 @ 04:23 pm
Last modified: Nov 20, 2018 @ 5:26 pm