What is a regulatory enzyme

Regulation of enzyme activity

Influence by external factors

The activity of an enzyme can be influenced by external factors such as temperature and pH value, as has already been explained on the relevant pages. However, there can be no question of regulation here.

End product inhibition

Let us consider a metabolic chain that consists of a starting material A, several intermediate products B, C, D and an end product E:

The end product is now able to produce the enzyme E.1 to inhibit. E.1 is the enzyme that catalyzes the first step in the metabolic chain.

When enough end product has been made, it would actually make sense for the cell to stop making E. Firstly, too much of the end product could be harmful to the cell; secondly, the synthesis costs energy and raw materials that could be used more meaningfully elsewhere.

How can a metabolic chain be stopped? Surely the last enzyme E4 are inhibited, then no end product would be created. But the disadvantage of this process would be that A continues to break down and intermediate products B, C and D are formed. Since D is no longer processed, there would be an accumulation of D in a short time with possibly negative consequences for the cell. In addition, raw materials and energy would continue to be consumed.

A more strategic point where the metabolic chain can be broken is the first enzyme in the chain, E1.

If E1 is inhibited, the substrate A is no longer degraded, and the intermediate products B, C, D and the end product E are no longer formed. No more raw materials or energy are wasted, and the intermediate products can no longer be accumulated in the cell.

In the end product inhibition of a metabolic chain, it is best if the first enzyme in the chain is inhibited.

The next question to deal with is this:

How and by what means should the first enzyme be inhibited?

The answer is actually very plausible: the inhibition should occur when the end product concentration has reached or even exceeded a certain value. So it also makes sense that enzyme E1 is inhibited by the end product itself.

Could E1 are not also inhibited by one of the intermediate products B, C or D?

Generally, yes! However, the concentration of the intermediate products B, C and D in the cell plasma is very low. As soon as the enzyme E1 has synthesized something B, the intermediate of the next enzyme becomes E.2 converted to C. So there is no accumulation of B. The same happens with the intermediate product C. As soon as the concentration of C is high enough, C molecules are transformed by the enzyme E.3 converted to D. And when the D concentration has reached a certain value, it does not rise any further, because now the last enzyme E comes4 the metabolic chain and converts D to the end product. Only the end product is not processed further (otherwise it would not be an end product) and can therefore accumulate in the cell. So not only does it make sense that the key enzyme E1 is inhibited by the end product, there is no other way!

In the case of the end product inhibition, this is the case first Enzyme of a metabolic chain through the End product self inhibited. The intermediate products are only present in very low concentrations because they are processed by the following enzymes. So you cannot inhibit the key enzyme at all.

End product inhibition mechanism

How exactly is the enzyme E1 inhibited by the end product, what is the mechanism of this inhibition?

In the last section we dealt with the influence of temperature and pH on enzyme activity. So if the end product managed to lower the temperature of the cell plasma or drastically change the pH value, the key enzyme E would certainly be inhibited1. But then also would all other The cell's enzymes are inhibited. When it comes to the end product inhibition, this should be the only thing first Enzyme of the metabolic chain are blocked. So there must be other mechanisms by which this goal can be achieved.

Competitive inhibition

If the end product has a similar structure to the starting material, what is known as competitive inhibition could take place: The end product E is located in the active center of the enzyme E.1, but cannot be further reduced. The higher the end product concentration, the more common the E1-Molecules blocked, and the less likely it is that an A molecule can be converted.

However, this great mechanism is tied to an important prerequisite: the inhibitor must look very similar to the actual substrate.

Competitive inhibition: A substance that looks very similar to the substrate of the enzyme but cannot be processed further by the enzyme settles in the active center of the enzyme and thereby reversibly blocks the enzyme.

The competitive inhibition is reversible. If the concentration of the actual substrate is very high and the concentration of the inhibitor is very low, the enzymes continue to work almost unhindered. However, if the concentration of the inhibitor is high and that of the substrate itself is low, the enzyme is increasingly inhibited. If the substrate concentration is then increased again, the enzyme activity increases. Substrate and inhibitor compete for the active site, the degree of inhibition depends on the ratio of substrate and inhibitor concentrations.

In the case of our metabolic chain with the four enzymes, however, competitive inhibition is very unlikely. The substrate A is rebuilt four times. The end product should not resemble the raw material at all, but should have a completely different structure.

A competitive inhibition by a substrate-like substance is therefore not an option as a mechanism for the end product inhibition, because the end product E most likely has a completely different structure than the substrate A.

Allosteric inhibition

As is well known, enzymes are globular proteins that consist of a large number of amino acids. The primary structure of the enzyme is superimposed by the secondary structure and the tertiary structure. The tertiary structure, i.e. the spatial arrangement of the amino acids, is of decisive importance for enzyme activity. The substrate settles in the active center of the enzyme according to the lock-and-key principle, and the enzyme is mostly substrate-specific, i.e. it only works optimally with a certain substrate. Other substances with a similar structure also fit into the active center, but are not processed at the optimum speed.

If the structure of the active center changes even a little, this has an immediate effect on the enzyme activity, as we already saw when we discussed the subject of "Influence of temperature and pH on enzyme activity".

With the end product inhibition, the end product E of the metabolic chain can now have the structure of the active center of the key enzyme E.1 change so that the enzyme activity of E1 is decreased.

To do this, the end product is placed in a special allosteric center of E1. This center is usually at a different point on the enzyme than the active center. When the end product moves into the allosteric center of E1 sets, the enzyme changes E1 its tertiary structure. This change in conformation (conformation = spatial arrangement of the atoms in a molecule) also affects the active center of the molecule; the active center changes its structure. The substrate A no longer fits so well into the active center, and the enzyme can no longer convert A as well as before: the enzyme activity drops.

Allosteric inhibition: An inhibitor (inhibitor) settles in the allosteric center of an enzyme. This changes the structure of the active center and the substrate can no longer be implemented as well.

In addition to the active center, an allosteric enzyme has a second center, the allosteric center. This can be occupied by an effector (key-lock principle). In the end product inhibition, an end product molecule takes on the role of the effector. An effector that has an inhibiting effect on enzyme activity is called an inhibitor.

If there is an inhibitor in the allosteric center, the enzyme is fixed in the inactive conformation. Only when the inhibitor leaves the allosteric center can the enzyme "fold back" into the active conformation and convert a substrate again.

The higher the concentration of the end product, the greater the proportion of inactive enzyme molecules and the lower the enzyme activity.

If for whatever reason the end product concentration begins to decrease again (e.g. because the end product is used up by another metabolic chain), the proportion of active enzyme molecules increases again and the end product is produced again. Until the end product concentration is too high again, the end product inhibition then starts again.

Substrate induction

In addition to the end product inhibition, the so-called substrate induction also very often occurs in metabolic chains. The key enzyme in the metabolic chain - usually the first enzyme - is inactive. It only becomes active when a sufficiently high number of substrate molecules is present in the medium. The enzyme is activated by the substrate itself.

This substrate induction can also take place via an allosteric center in the enzyme. A substrate molecule acts as an activator in the allosteric center, the enzyme changes its conformation (tertiary structure), which also affects the active center. In this changed conformation, a Substat molecule can now also be placed in the active center, which was previously not possible due to the structure of the enzyme.

Enzyme regulation and gene regulation

Many important enzymes are actually regulated in their activity in the manner described here by substrates or end products. Much more powerful, however, is the regulation of enzyme activity at the genetic level. For example, when bacteria are placed in a nutrient medium that is rich in lactose (a double sugar made up of galactose and glucose, also known as milk sugar), they start making enzymes that can break down lactose. This means that the enzymes are only produced when required. In order to achieve this, certain genes are activated, on which the information for the production of these enzymes is located.

The subject of gene regulation is not yet (or hardly at all) dealt with in the EF level, because it is quite complex. If you are still interested, please have a look at my pages on gene regulation.