Enzymes are involved in a wide variety of metabolic processes and are essential for an organism. In order to be able to regulate these processes, however, the cells need certain mechanisms that influence the activity of the enzymes. These can work in different ways.
The activity of enzymes can be influenced, for example, by binding certain substances, namely the so-called effectors. Depending on how they act on an enzyme, effectors are divided into activators or inhibitors. While the activators increase the activity of enzymes, the inhibitors decrease the activity. The inhibitors are therefore responsible for the enzyme inhibition.
What is enzyme inhibition?
An enzyme inhibition, rarely also called enzyme inhibition, is the inhibition of an enzymatic reaction by an inhibitor, namely the inhibitor just mentioned. In the case of enzyme inhibition, the activity of the enzyme is reduced and the speed of the catalyzed reaction is thus reduced.
The inhibitors bind to various reactants, for example to the enzyme or to the substance to be converted, also known as the substrate. Exactly where the inhibitor binds depends on the type of inhibition.
The consequence of the enzyme inhibition is that the enzyme can either only convert the substrate to the product very slowly or not at all. Enzyme inhibition thus plays an important role in the regulation of metabolism in all living things.
There are several types of enzyme inhibition. In most cases, the classification is made into reversible (reversible) and irreversible (irreversible) enzyme inhibitions.
Reversible enzyme inhibition
The reversible inhibition is reversible because the inhibitor can be released from the enzyme again, i.e. it does not bind tightly to the enzyme. In general, the reversible form of enzyme inhibition is often used to regulate various metabolic processes that are not always supposed to take place.
The reversible enzyme inhibition can in turn be divided into different subtypes:
- competitive inhibition
- non-competitive inhibition
- uncompetitive inhibition.
Competitive enzyme inhibition
In competitive enzyme inhibition, the inhibitor binds to the active site of an enzyme, i.e. it competes with the substrate for a place on the enzyme. The inhibitor has a similar structure to the substrate to allow it to bind to the active site. This is also referred to as the so-called substrate analogue. However, the structure differs to such an extent that the enzyme does not confuse the inhibitor with the substrate. For this reason, the inhibitor is not converted into products by the enzyme.
The competitive inhibition is reversible because the inhibitor can be displaced from the active center of the enzyme again by increasing the substrate concentration.
Non-competitive enzyme inhibition
In non-competitive inhibition, the inhibitor does not bind to the active site of the enzyme but to a different site. This is usually the so-called allosteric center. In this case, non-competitive inhibition is also called allosteric inhibition.
Consequently, since the non-competitive inhibitor binds to a different site than the substrate, it does not compete directly with the substrate for place on the enzyme. Instead, it inhibits the reaction by changing the shape of the active center by docking onto the enzyme. As a result, the substrate that would have actually fitted the spot can no longer bind to the enzyme, or only with difficulty.
Non-competitive inhibition is also reversible because the inhibitor can detach itself from the enzyme. As a result, the active center of the enzyme returns to its original shape and the appropriate substrate can bind to the enzyme again.
In the following picture you can see in simplified form the various binding sites of the inhibitor (abbreviated with I) to the enzyme (E) and the consequences for the substrate (S). In competitive inhibition (left), the substrate cannot bind to the enzyme because the inhibitor docks at the same site. In non-competitive inhibition, the substrate and inhibitor do not compete for space on the enzyme, but the substrate can no longer bind there due to the change in the structure of the active site.
via wikipedia.org
end product inhibition
A special form of allosteric enzyme inhibition, in which the end product inhibits the enzyme that leads to the synthesis of this substance, is also called end product inhibition or feedback inhibition. For example, glycolysis is used to produce energy from glucose. One enzyme involved in glycolysis is pyruvate kinase, another is phosphofructokinase. If there is a lot of energy in the cell, it has stored it in the form of adenosine triphosphate (ATP). As an inhibitor, this ATP inhibits phosphofructokinase and also pyruvate kinase. This means that no more glucose is converted into energy, i.e. ATP.
Uncompetitive enzyme inhibition
With this type of inhibition, too, the inhibitor does not bind to the active center of an enzyme, but rather to its own binding site. However, the difference to non-competitive inhibition is that the uncompetitive inhibitor only binds to the enzyme when an enzyme-substrate complex has already been formed, i.e. when the substrate is already docked to the enzyme. The inhibitor also changes the shape of the active site, but only in the enzyme-substrate complex. The substrate is thus levered out, so to speak.
This type of enzyme inhibition can also be reversed by reducing the substrate concentration. The reason for this is that the fewer such complexes are present, the less often the inhibitor can bind to an enzyme-substrate complex.
An example of an uncompetitive inhibitor is the herbicide glyphosate. Glyphosate inhibits an enzyme called EPSP synthetase. This is responsible for an important metabolic pathway in plants. The EPSP synthetase catalyzes a reaction that produces the amino acids necessary for plants. If the amino acids cannot be formed, the plant dies. Glyphosate can therefore be used in agriculture to kill weeds.
Irreversible enzyme inhibition
In irreversible inhibition, the inhibitor binds so tightly or covalently that it can no longer be detached from the enzyme. The activity of the enzyme is then lost and it remains inactive forever. The irreversible inhibition can be found, for example, in fungi that produce antibiotics to protect them. These antibiotics often irreversibly inhibit certain metabolic pathways, such as protein biosynthesis.
Another well-known example is the antibiotic penicillin. Penicillin permanently inhibits the enzyme that is responsible for forming the cell wall in bacteria. As a result, the bacterial cells no longer have any stability and can no longer divide. The antibiotic prevents the bacteria from multiplying.
Irreversible enzyme inhibition also often occurs in the case of poisoning by nerve gases or heavy metals such as mercury.
Everything you need to know about enzyme inhibition at a glance!
- The enzyme inhibition is important so that the numerous metabolic processes in the organism can be regulated.
- Enzyme inhibition means the inhibition of an enzymatic reaction by an inhibiting substance, also called an inhibitor. The activity of the enzyme is reduced and the speed of the catalyzed reaction is thus reduced.
- The inhibitors bind, for example, to the enzyme or to the substance to be converted (= substrate).
- There are reversible (reversible) and irreversible (irreversible) enzyme inhibitions.
- Reversible enzyme inhibition can in turn be divided into different subtypes, namely competitive inhibition, non-competitive inhibition and uncompetitive inhibition.
- The result is that the enzyme can (temporarily) no longer convert the substrate.
- In irreversible inhibition, the inhibitor binds so tightly that it can no longer be detached from the enzyme. The activity of the enzyme is then lost and it remains inactive forever.