What is Allosteric Enzyme?

Allosteric enzymes are enzymes that have an additional binding site for effector molecules other than the active site. The binding brings about conformational changes, thereby changing its catalytic properties. The effector molecule can be an inhibitor or activator.

All the biological systems are well regulated. There are various regulatory measures in our body, that control all the processes and respond to the various inside and outside environmental changes. Whether it is gene expression, cell division, hormone secretion, metabolism or enzyme activity, everything is regulated to ensure proper development and survival.

Allostery is the process of enzyme regulation, where binding at one site influences the binding at subsequent sites.

Allosteric Enzyme Properties

  • Enzymes are the biological catalyst, which increases the rate of the reaction
  • Allosteric enzymes have an additional site, other than the active site or substrate binding site. The substrate-binding site is known as C-subunit and effector binding site is known as R-subunit or regulatory subunit
  • There can be more than one allosteric sites present in an enzyme molecule
  • They have an ability to respond to multiple conditions, that influence the biological reactions
  • The binding molecule is called an effector, it can be inhibitor as well as activator
  • The binding of the effector molecule changes the conformation of the enzyme
  • Activator increases the activity of an enzyme, whereas inhibitor decreases the activity after binding
  • The velocity vs substrate concentration graph of allosteric enzymes is S-curve as compared to the usual hyperbolic curve

Allosteric Regulation Mechanism

There are two types of allosteric regulation on the basis of substrate and effector molecules:

Homotropic Regulation: Here, the substrate molecule acts as an effector also. It is mostly enzyme activation and also called cooperativity, e.g. binding of oxygen to haemoglobin.

Heterotropic Regulation: When the substrate and effector are different. The effector may activate or inhibit the enzyme, e.g. binding of CO2 to haemoglobin.

On the basis of action performed by the regulator, allosteric regulation is of two types, inhibition and activation.

Allosteric Inhibition: When an inhibitor binds to the enzyme, all the active sites of the protein complex of the enzyme undergo conformational changes so that the activity of the enzyme decreases.

Allosteric Activation: When an activator binds, it increases the function of active sites and results in increased binding of substrate molecules.

There are two models proposed for the mechanism of regulation of allosteric enzymes:

  1. Simple Sequential Model

    It was given by Koshland. In this model, the binding of substrate induces a change in the conformation of the enzyme from T (tensed) to R (relaxed). The substrate binds according to the induced fit theory. A conformational change in one unit stimulates similar changes in other subunits. This explains the cooperative binding.

    The same way inhibitors and activators bind, the T form is favoured, when the inhibitor binds and R form is favoured, when the activator binds. The binding at one subunit affects the conformation of other subunits.

    The sequential model explains the negative cooperativity in enzymes, e.g. tyrosyl tRNA synthetase, where the binding of substrate inhibits the binding of another substrate.

  2. Concerted or Symmetry Model

    This model was proposed by Monad. According to this model, there is a simultaneous change in all the subunits of an enzyme. All the subunits are either present in R form (active form) or T form (inactive form), that have more affinity and less affinity to a substrate, respectively.

    An inhibitor shifts the equilibrium of T ⇄ R, towards T, and activator shifts the equilibrium towards R form and favours the binding. It explains the cooperative regulation of activators as well as inhibitors.

Examples of Allosteric enzyme

There are many allosteric enzymes that take part in the biochemical pathways so that the system is well controlled and modulated.

  1. Aspartate Transcarbamoylase (ATCase)
    • ATCase catalyses the biosynthesis of pyrimidine
    • Cytidine triphosphate (CTP) is the end product and also inhibits the reaction. It is known as feedback regulation
    • ATP (adenosine triphosphate), a purine nucleotide activates the process, high concentration of ATP can overcome inhibition by CTP
    • This ensures the synthesis of pyrimidine nucleotide when a high concentration of purine nucleotide is present
  2. Glucokinase
    • It plays an important role in glucose homeostasis. It converts glucose to glucose-6-phosphate and enhances glycogen synthesis in the liver. It also senses the concentration of glucose for the release of insulin from pancreatic beta cells
    • The glucokinase has low affinity for glucose, so it acts when more concentration of glucose is present in the liver, which should be converted to glycogen
    • The activity of glucokinase is regulated by glucokinase regulatory proteins
  3. Acetyl-CoA Carboxylase
    • Acetyl-CoA carboxylase regulates the process of lipogenesis
    • This enzyme is activated by citrate and inhibited by a long chain acyl-CoA molecule such as palmitoyl-CoA, which is an example of negative feedback inhibition by product
    • Acetyl-CoA carboxylase is also regulated by phosphorylation/ dephosphorylation controlled by hormones such as glucagon and epinephrine

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