Allosteric Enzymes

A group of biocatalysts that possess similar characteristics of an enzyme but do not exhibit a typical Michaelis-Menten kinetic behaviour is called allosteric enzymes. Instead, their kinetics follow a sigmoid curve. All the biological systems are well regulated. There are numerous regulatory measures in our body that control all the processes and respond to the different inside and outside environmental changes. It may be gene expression, cell division, hormone secretion, metabolism or enzyme activity, everything is regulated to ensure proper development and survival. Allostery is the regulatory enzyme, where binding at one site influences the binding at other sites.

What are Enzymes?

Enzymes are a kind of protein that is present in all types of living organisms. They are mainly secreted by a source and work as a catalyst in living organisms. They mainly guide various biochemical reactions occurring inside organisms. They are mainly produced by plants, animals, bacteria and fungus. As they act as a catalyst where they convert the substrate into different molecules which are known as products. Almost all metabolic reactions need enzymes for their catalyses. Enzymes are known to catalyse more than 5,000 biochemical reactions inside the body.  

What are Allosteric Enzymes?

It is a kind of enzyme which can change their structural ensemble when they bind to an effector i.e allosteric modulator, by which they can change their binding affinity at a different ligand binding site. They play a major role in various biological processes. There is a specific site to which the effector binds known as allosteric site.This site mainly allows the effector to bind to the protein, which results in conformational changes involving protein dynamics process.

Allosteric term mainly refers to the regulatory site of an allosteric is physically distinct from its active site.

Properties of Allosteric Enzymes

There are several unique properties of Allosteric enzymes, which makes it unique from other enzymes. Some of these properties are given below:

1. There is one allosteric enzyme that does not follow Michaelis-Menten Kinetics. Reason behind this is that they have multiple active sites and these active sites have cooperativity property i.e where the binding of one active site affects the binding of other active sites on the enzyme. Due to this other affected site's graph of allosteric enzymes is a sigmoidal curve.

2. They show mainly substrate concentration type of property. Example: at high concentration of substrate, maximum enzymes are found in the R state. But when there is insufficient amount of substrate present that time T is the favorite state. So, we can say that equilibrium of  both T and R states depends on concentration of substrate.

3. Other molecules can regulate allosteric enzymes. 

4. They have capability to respond to multiple conditions which inchances biological reactions.

5. There are activators in allosteric enzymes which increase activity enzymes, whereas inhibitors decrease the activity of enzymes. 

6. Binding of molecules is called an effector, it can be both inhibitors or activators.

7. When the effector binds with molecules they change their conformational property of the enzymes. 

8. Enzymes increase the rate of the reaction, since they are biological catalysts.

9. There can be multiple allosteric sites in an enzyme molecule

10. They have an ability to respond to different conditions, that influence the biological reactions

11. The binding molecule is called an effector, it can be an inhibitor or an activator

12. The binding of the effector molecule will change the conformation of the enzyme

13. The activity of an enzyme is increased by the activator, whereas activity is decreased by the inhibitor after binding

14. The allosteric enzymes of the velocity vs substrate concentration graph are S-curve as compared to the usual hyperbolic curve.

Allosteric Mechanism Regulation

We can regulate allosteric enzymes on the basis of types i.e one for substrate and other for effector molecules.

Two types of allosteric regulation are:

1. Homotropic Regulation: In this type of regulation substrate molecules act as an effector also. They are mainly enzyme activation and known as cooperativity. Example of homotropic regulation is binding of oxygen to haemoglobin.

2. Heterotropic Regulation: This is a kind of regulation where substrate and effector are different. Example of heterotropic regulation is binding of carbon dioxide(co2)  to haemoglobin.

On the basis of the above action performed by the regulator, there are two types of regulation one is activator and other is inhibitors.

Allosteric Inhibition: Under this process inhibitors bind with protein due to which all active sites of protein undergo conformational changes due to which activity of enzyme decreases.

Allosteric Activation: Under this process activator binds with protein which increases the function of active sites leads to increase in enzymatic activity.

Models Based of Allosteric Enzymes Regulation

There are so many modals which are proposed on mechanism of allosteric enzymes, some of these model are given below:

1. Simple Sequential Model: This model was proposed by Koshland. In this model due to binding of substrates there is a change in conformation of the enzymes from T( Tensed) to R (relaxed). Their substrate binds are per induced fit theory.

2. Concerted or Symmetry Model: This model was proposed by Monad. As per this model there is a simultaneous change in all subunits of enzymes. Example: Tyrosyl tRNA synthetase, in this binding of one substrate, inhibits the binding of other substrates.

Examples of Allosteric Enzymes

There are so many allosteric enzymes that help in various biochemical reactions occurring inside the body. Some of the well known allosteric names are given below:

1. Glucokinase:

1. It plays a major role in homeostasis of glucose as it converts glucose to glucose-6-phosphate and increases glycogen synthesis inside the liver.

2. It also maintains concentration of glucose into the blood.

3. Their activity is regulated by glucokinase regulatory proteins.

2. Aspartate Transcarbamoylase:

1. They mainly catalyse the biosynthesis of pyrimidine.

2. They maintain the level of pyrimidine synthesis when purine concentration becomes high.

3. Acetyl-CoA Carboxylase:

1. They regulate the process of lipogenesis.

2. Citrate activates the functioning of these enzymes and it is inhibited by long chain acyl-CoA-molecule products.

3. It is regulated by phosphorylation which is controlled by hormones like glucagon and epinephrine.

Examples of Allosteric Enzymes

The activity of an allosteric enzyme is pacified to the presence of its effector and the kinetics to the concentration of the effector. This effector-dependency offers allosteric enzymes not only to switch their activity on or off but also a checkpoint for reserving feedback that modifies the metabolic activity in reply to the cellular signals.

Phosphofructokinase (PFK)

Phosphofructokinase (PFK) is the key monitoring enzyme in glycolysis and the cellular production of energy from the disintegration of carbohydrate molecules. Glycolysis results in the generation of pyruvate and high-energy molecules, adenosine triphosphate (ATP).

Isocitrate dehydrogenase (IDH)

Isocitrate dehydrogenase (IDH) catalyzes the primary regulatory part of the citric acid cycle. Also known as the Krebs cycle or the tricarboxylic acid (TCA) cycle, it is the regulatory pathway in aerobic metabolism, which gains energy from the embarrassment of acetyl CoA and provides building units for the biosynthesis of amino acids, heme, and nucleic acids. Human IDH has two sets of heterodimers, one acts as a catalytic subunit and the other as the regulatory subunit.

Aspartate transcarbamoylase (ATCase)

Aspartate transcarbamoylase (ATCase) is the enzyme that facilitates the flow limit and committed step of pyrimidine biosynthesis. The pathway generates pyrimidine, which is a component of nucleic acids. ATCase contains a large catalytic subunit and a smaller regulatory subunit.