Allosteric Enzymes and Regulation – Functions, Structure and Kinetics

Allosteric Enzymes These are organic chemicals that are made up of a structure of four molecules, which is why it is said to be quaternary.

As a result, allosteric enzymes have more than one polypeptide chain and contain catalysis units. They, in turn, also have an activity site, that is, a chemical exchange, and for this reason, they perform substrate recognition.

In other words, allosteric enzymes are characterized by the presence of more than two polypeptide chains, whose subunits have different properties: one isostere, which is an active site in itself, and one allosteric, where the enzyme is regulated.

The latter does not have catalytic activity, but it can be associated with a modulation molecule that can act as a stimulus or hinder the implementation of enzyme activity.


A Brief Introduction to Allosteric Enzymes

Allosteric enzymes have an important role in facilitating digestion. As they penetrate into the nucleus of molecules, these enzymes are able to interfere with the body’s metabolism, so they are able to force it to be absorbed and excreted in accordance with arising biochemical needs.

This requires that allosteric enzymes move the mechanisms by which the regulatory process is carried out.

These enzymes are classified in two aspects: K and V. In both cases, it is usually seen that their saturation curve is usually not hyperbole, but has an irregular shape that mimics the sigma of the Greek alphabet.

This, of course, means that its structure and kinetics do not coincide at all with those of Michelan enzymes, and much less than that of non-allosteric enzymes, since its substrate causes corresponding variations and differences in the reaction rate.

The structure and kinetics of allosteric enzymes are directly related to cooperative interactions, especially non-covalent ones.

This assumption is based on the premise that the sigmoid curve, which is drawn as the substrate concentration increases, is associated with structural changes that occur with enzymes.

However, this correlation is not always absolute and allows for ambiguities in which certain features in this system are omitted.


Function of allosteric enzymes

All over the world, allosteric enzymes are called molecules of organic origin, in which they can influence the biochemical bonds between proteins and enzymes ..

The action of these allosteric enzymes develops through infiltration into the molecular core, so that inside the body it is responsible for digestive catalysis. Thanks to this, various processes associated with the gastrointestinal tract are expanded, especially in the management of metabolism.

Hence, the main function of allosteric enzymes is to facilitate digestion in the body. This is because the referencing process to which they are presented allows the absorption of nutrients as well as the elimination of waste in the body’s structure.

Therefore, catalysis of the digestive system develops continuously in a balanced environment, in which each modulator has a certain allosteric site.

In addition, allosteric enzymes, in terms of metabolism, are those that achieve that the enzymatic activity is controlled by vibrations that are perceived at the layer level.

The fewer changes made to the concentration of this substrate, the more transformations that enzyme activity will undergo, and vice versa.

On the other hand, the values ​​of allosteric K enzymes can be increased by using a minimum dose of an inhibition modulator.

It may happen that, by their characteristics, allosteric enzymes are inhibited at the end of the metabolic process, which occurs in some multienzyme systems (they have many types of enzymes), which is much more if the cellular capacity is exceeded.

When this happens, allosteric enzymes provide a decrease in catalytic activity; otherwise, the substrate activates enzymatic activity instead of regulating it.


Allosteric regulation

It is known as those cellular processes in which enzymatic activity is regulated by a regulatory process. This is possible due to the fact that feedback is created, which can be positive (that is, activation) or negative (inhibition).

Regulation can occur in different ways, either on an organic scale (supracellular, above the cell), by signal transduction and covalent modification of enzymes.

Substrate fixation can usually occur at the active site when no inhibitor is present.

However, if this allosteric center is occupied by an inhibitor, this first element changes in its structure and, therefore, the substrate cannot be fixed.

The presence in the form of sigmoid kinetics suggests that there is a co-operative relationship in the substrate, but this is not always the rule, there are exceptions (see the section “Allosterism and Co-operatives?: Synonyms” below).


Structure And Kinetics of Allosteric Regulation

Some of the allosteric enzyme polypeptides do not require catalysis. In any case, they also have strategic and very specific sites at which the binding and recognition of the modulator takes place, so a complex modulation enzyme can arise.

This is due to the fact that its greater or lesser catalysis activity depends on the polarity of the modulator, that is, on whether it is a negative pole (inhibition pole) or a positive pole (activation pole) ..

The place where this biochemical exchange, or, rather, the enzymatic interaction with the modulator, takes place, is rightfully called the allosteric site.

Here, their properties are retained without changing the modulator at the chemical level. However, the link between the modulator and the enzyme is not irreversible, rather the opposite; This can be canceled. Hence, it can be said that this allosteric enzyme process is not stationary.

The peculiarity of allosteric enzymes is that they do not correspond to the kinetic laws that correspond to the Michaelis-Menten principles.

In other words, experiments so far have shown that the relationship between the allosteric enzyme and modulators (regardless of its polarity) has a saturation curve that is regular, but sigmoidal, with a similar curvature to the Greek letter sigma.

Differences in this sigmoid shape are few, regardless of whether modulators (positive or negative) were used or not used at all.

In all cases, the rate of reactions of allosteric enzymes demonstrates a number of dramatic modifications, in which the substrate concentration is lower in comparison with negative modulators and higher with positive ones. In turn, they have intermediate values ​​when there are no enzyme-related modulators.

The kinetic behavior of allosteric enzymes can be described using two models: symmetric and sequential.


Symmetrical model of allosteric enzymes

In this model, the allosteric enzyme can be represented according to conformations that are tense and relaxed.

The subunits can be at one end or the other, as there is a balance that shifts between both states, in which negative modulators approach a tight conformation, while a relaxed one connects substrates and activators.

Sequential model of allosteric enzymes

With this model, you have a different paradigm. There are also two conformations here, but each can act independently, separately.

At this point, there may be an increase or decrease in the affinity of the biochemical bonds of enzymes with levels of cooperativity that may have activation or inhibition.

Structural changes are transferred sequentially from one department to another in a specific order.

Both symmetrical and sequential models work independently according to their own standards. However, both models can work together, hence they are not mutually exclusive.

In these cases, intermediate states in which conformations are observed as, i.e. relaxed tense and participate in a joint process in which the biochemical interactions of allosteric enzymes are given melt.

Alosterism and the cooperative: synonyms?

It was believed that alosterism was the same as cooperativism, but it is not. The confusion of both terms seems to stem from their function.

However, it should be noted that this similarity is not enough for alosterism and cooperativism to be used as equivalent words. Both have subtle nuances that you should pay attention to before falling into incorrect generalizations and categorizations.

It should be remembered that allosteric enzymes take different forms when attached to modulators. Positive modulators are activated and negative modulators inhibit.

In both cases, there is a significant change in the enzymatic structure in the active site, which, in turn, becomes a change in the same active site.

One of the most practical examples of this is noncompetitive inhibition, in which a negative modulator binds to an enzyme other than the substrate.

However, the affinity of this enzyme for the substrate can be reduced by this negative modulator of allosteric enzymes, so it can become competitive inhibition regardless of whether the structure of the substrate differs from that of the enzyme.

Likewise, it may happen that there is an increase in said affinity or that instead of an inhibitory effect, the opposite effect occurs, that is, an activation effect.

The phenomenon of cooperativism occurs in many allosteric enzymes, but it becomes cataloged as such only when the enzymes have several places where they manage to bind to the substrate, which is why they are called oligomeric enzymes ..

In addition, affinities are created in accordance with the level of concentration that the effector has, and in them positive modulators, negative and even the substrate itself act in different ways throughout this process ..

To create this effect, it is necessary to present several sites capable of binding to the substrate, and the result in scientific research is graphically represented in the form of sigmoid curves, which have already been mentioned.

And this is where the confusion comes in, because it tends to associate with the fact that if there is a sigmoid curve in an enzymatic assay, it is because the observed allosteric enzyme must necessarily be cooperative.

Moreover, one of the factors contributing to this confusion is that the degree of cooperativity that exists in the system is governed by allosteric effectors.

Its level can increase with the presence of inhibitors, while it tends to decrease when activators are present.

However, kinetics leaves its sigmoid state only when it becomes michaeliana in which the activator concentrations are increased.

Therefore, it is clear that sigmoid curves can be antonyms of allosteric enzymes. Although most of these enzymes, when this substrate is saturated, have this signal, it is not true that allosteric interaction occurs only because the graph shows the curvature of sigmoidal kinetics.

To assume that the opposite is also wrong; sigmoid does not mean from pronounced to obvious manifestation of alosterism.


Unique alosterism: hemoglobin

Hemoglobin is considered a classic example of what happens to allosteric systems. In this component of erythrocytes, a substrate corresponding to the sigmoid type is fixed.

This fixation can be suppressed by effectors in which there is no action on the active center, which is none other than the heme group. On the other hand, Mikhailovskaya kinetics is presented separately in the subunits involved in oxygen fixation ..