A Key Note on Allosteric Enzyme

AN INTRODUCTION: WHAT IS ALLOSTERIC ENZYMES?

All biological systems are in good working order. In our bodies, there are different regulatory mechanisms that manage all processes and respond to internal and external environmental changes. Everything is regulated to maintain healthy development and survival, whether it’s gene expression, cell division, hormone release, metabolism, or enzyme function. Allostery is an enzyme regulatory process in which binding at one location influences binding at other sites.

Properties of Allosteric Enzymes

Enzymes are a type of biological catalyst that speeds up the reaction.

Other than the active site and the substrate binding site, allosteric enzymes contain a third site. The C-subunit binds to the substrate, while the R-subunit, or regulatory subunit, binds to the effector.

In an enzyme molecule, there might be more than one allosteric site.

They have the ability to respond to a variety of circumstances that influence biological processes.

An effector is a binding molecule that can be both an inhibitor and an activator.

The binding of the effector molecule alters the enzyme’s conformation.

After binding, an activator raises the activity of an enzyme, whereas an inhibitor decreases it.

In contrast to the conventional hyperbolic curve, the velocity versus substrate concentration graph of allosteric enzymes is an S-curve.

Mechanism of Allosteric Regulation

On the basis of substrate and effector molecules, there are two forms of allosteric regulation: Homotropic Control: In this case, the substrate molecule also serves as an effector. It is usually enzyme activation, which is also known as cooperativity, for example, oxygen binding to haemoglobin. Heterotropic Control: If the substrate and effector are not the same. The effector, such as CO2 binding to haemoglobin, can either activate or inhibit the enzyme. Allosteric regulation is divided into two sorts based on the regulator’s action: inhibition and activation. When an inhibitor binds to an enzyme, all of the active sites in the enzyme’s protein complex undergo conformational changes. As a result, the enzyme’s activity drops. To put it another way, an allosteric inhibitor is a chemical that binds to an enzyme only at an allosteric location. 

Activation by allosteric means: When an activator attaches, it improves the function of active sites, resulting in more substrate molecule binding. For the regulation of allosteric enzymes, two models have been proposed:

Koshland proposed the Simple Sequential Model. The binding of substrate causes the enzyme’s, The T form is preferred when the inhibitor binds, and the R form is preferred when the activator binds, in the same way as inhibitors and activators bind. The conformation of other subunits is affected by the binding of one subunit. The sequential model explains negative cooperativity in enzymes, such as tyrosyl tRNA synthetase, where substrate binding inhibits substrate binding.

Symmetry or Concerted Model-

According to this idea, all of an enzyme’s subunits change at the same time. All of the subunits exist in either R (active) or T (inactive) forms, with the latter having a lower affinity for a substrate. The equilibrium of T R is shifted towards T by an inhibitor, while the equilibrium is shifted towards R by an activator, favouring binding. conformation to change from T (tensed) to R (relaxed) in this model (relaxed). According to the induced fit theory, the substrate binds. A conformational shift in one unit causes other subunits to alter as well. The cooperative binding is explained in this way. It illustrates how activators and inhibitors work together to regulate each other.

Examples of Allosteric Enzymes

Many allosteric enzymes participate in biochemical pathways, allowing the system to be well-controlled and modulated. Transcarbamoylase of Aspartate (ATCase)

Pyrimidine biosynthesis is catalysed by ATCase.

The end product, cytidine triphosphate (CTP), also inhibits the process. It’s known as ATP (adenosine triphosphate) feedback regulation; a purine nucleotide initiates the activity, and a high concentration of ATP can overcome CTP inhibition.

When a high concentration of purine nucleotide is present, this ensures the synthesis of pyrimidine nucleotides. 

Glucokinase

It’s crucial for glucose homeostasis to work properly. It increases glycogen production in the liver by converting glucose to glucose-6-phosphate. It also detects glucose levels in order for pancreatic beta cells to release insulin.

Because glucokinase has a limited affinity for glucose, it only activates when there is a high quantity of glucose in the liver that has to be converted to glycogen.

Glucokinase activity is controlled by glucokinase regulatory proteins.

Carboxylase of acetyl-CoA

The enzyme acetyl-CoA carboxylase controls lipogenesis.

Citrate activates this enzyme, which is blocked by a long chain acyl-CoA molecule like palmitoyl-CoA, which is an example of negative feedback inhibition by product.

Acetyl-CoA carboxylase is also influenced by hormones that affect phosphorylation and dephosphorylation, such as glucagon and epinephrine.

CONCLUSION

There are numerous allosteric enzymes involved in metabolic pathways. Aspartate Transcarbamoylase, Glucokinase, and Acetyl-CoA Carboxylase are other examples. Quaternary structure is found in enzymes with many subunits. Individual catalytic subunits have their unique active site as a result of the many subunits. This means that a quaternary structure enzyme can bind several substrate molecules.