Competitive (reversible) inhibition
The drug pirlindole is a classic example of a reversible inhibitor. Structurally, it is a structural analogue of the natural neurotransmitter serotonin. Due to this similarity, the medicinal substance is able to bind to the active site of the enzyme.
The biochemical essence of the process lies in direct competition. The enzyme (denoted as E) has a choice: it can bind either with the natural substrate (S), forming the ES complex, which then breaks down into the free enzyme and product (P), or with the inhibitor molecule (I), forming the EI complex.
- Normal reaction scheme: $E + S \rightleftarrows ES \rightarrow E + P$
- In the presence of pirlindole: $E + I \rightleftarrows EI$
A key feature of this type of interaction is the formation of a weak bond. This means that the blockade is temporary. As soon as the concentration of the drug in the body begins to decrease (as it is naturally eliminated), the enzyme-inhibitor complex dissociates. Enzyme activity is fully restored without the need to synthesize new protein molecules.
Irreversible inhibition
The drug nialamide demonstrates a completely different mechanism of action. Unlike structural analogues of the substrate, it causes irreversible inhibition of enzymatic activity.
When an enzyme molecule (E) and an inhibitor (I) meet, a chemical reaction occurs, resulting in the formation of strong covalent bonds with functional groups located in the active site.
- Inactivation scheme: $E + I \rightarrow E-I$
This reaction is a covalent modification. The resulting EI complex is stable and no longer dissociates under any conditions. The enzyme is permanently put out of action because its active site is physically blocked and structurally altered.
Comparison of therapeutic effect duration
The difference in biochemical mechanisms directly determines how long the clinical effect of taking the drugs lasts in patients.
Pirlindole is characterized by a relatively short duration of action. Since the inhibition is reversible, the drug's effect directly depends on its current concentration in tissues. As soon as the drug is eliminated from the body, the enzymes are released and immediately resume their work.
Nialamide has a much longer-lasting effect on the body. Since the enzyme molecules are irreversibly inactivated, simply clearing the medicinal substance from the bloodstream does not return the system to its initial state. Activity will not recover until cells synthesize brand-new enzyme molecules. This physiological process of protein biosynthesis takes a significant amount of time and can take up to two weeks. Throughout this time, the therapeutic effect persists despite the absence of the drug itself in the body.
Briefly: answers to topical questions
Which other neurotransmitters besides serotonin are broken down by the MAO enzyme?
In addition to serotonin, the monoamine oxidase (MAO) enzyme inactivates dopamine, norepinephrine, and GABA via oxidative deamination. FAD serves as the coenzyme for MAO.
Stages of conversion:
- biogenic amine loses ammonia ($NH_3$) under the action of $O_2$;
- an aldehyde ($R-C=O$) is formed;
- the aldehyde is oxidized to an acid ($R-COOH$), which is excreted by the kidneys.
MAO isoenzymes differ in substrate specificity: MAO-A predominantly inactivates norepinephrine and serotonin, while MAO-B inactivates dopamine.
Pirlindole — Pemporary (reversible, competes temporarily). Nialamide — Never again (irreversible, covalent bonds).
Class and exam questions
Why can enzyme activity recover on its own when taking pirlindole?
Pirlindole forms a weak bond with the active site of the enzyme. When the drug concentration in the medium decreases, this bond breaks, the complex dissociates, and the active site is ready to accept the neurotransmitter again.
What causes the prolonged action of nialamide?
Nialamide forms strong covalent bonds with the functional groups of the active site. The enzyme is irreversibly modified and inactivated permanently. The effect of the drug lasts until new proteins are synthesized.
How long does it take for activity to recover after irreversible inhibition?
The process of cellular biosynthesis of new protein molecules to replace the blocked ones takes up to 2 weeks.
What else to study on this topic
- Enzyme reaction kinetics in reversible inhibition
- Mechanisms of covalent enzyme modification
- Stages of cellular protein biosynthesis (using the turnover of the enzyme pool as an example)
- The role of serotonin as a substrate for enzymatic systems
Master the entire topic in the "Biochemistry" course
This is a summary. The course covers everything tested in classes and exams.
- Full study guide on "MAO Inhibitors" and 3,616 more subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 115 video lessons on the subject
Other topics in the "Enzymology" section
Free video lessons: biochemistryShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.