Allosteric Enzymes

Allosteric enzymes (the Greek word " allo" means other and " steric" means place of sight) are a class of regulatory enzymes that increase or decrease catalytic activities in response to certain signals. They function through reversible, noncovalent binding of regulatory compounds called modulators or effectors. 

1.0Introduction

The two Nobel Laureates, Monad and Jacob, introduced the term allosteric to denote an enzyme site different from the active site that non-competitively binds a molecule other than the substrate and may influence the enzyme activity.

Most allosteric enzymes are oligomeric ( consisting of multiple subunits) and may have two functionally different binding sites. One of the sites is the active site, which binds the substrate and catalyzes the reaction. 

The other type of site, known as allosteric or regulatory site, binds with a molecule called a moderator. Moderator molecules are of two types 

1. Positive modulator( activator) 

2. Negative modulator ( inhibitors)

Also Check: Chemical Coordination And Integration

2.0Types of Allosteric Regulation

1. Homotropic

• A homotropic allosteric modulator is both the substrate for its target enzyme and a regulator of the enzyme's activity, often serving as an activator. 
• A classic example is oxygen (O₂), which functions as a homotropic allosteric effector for haemoglobin in the human body.

2. Heterotropic

• A heterotropic allosteric modulator is a regulator molecule that is not also the enzyme's substrate. It may be an activator or an inhibitor of the enzyme it binds to. 
• For example, H⁺, CO₂ and 2,3,- biphosphoglycerate are heterotropic allosteric modulators of haemoglobin.

3.0Model of Allosteric Regulation

• Two main models have been proposed to describe the mechanistic basis of enzyme allostery.
• Concerted Symmetry Model (MWC model): Given by Monod, Whyman and Changeux 
• Sequential model (KNF Model): Given by Koshland, Nemethy and Filmer

1. Monod, Whyman and Changeux Model / Concerted Symmetry Model

• MWC has a pre-existing equilibrium between R and T forms without ligands. 
• The substrate or activator binds preferentially to the R form. 
• All subunits must be in the same conformation; only two possible conformations exist. 
• All subunits change conformation together; the mechanism is called the concerted or symmetry model.

2. Koshland, Nemethy and Filemer (KNF Model)

• In KNF, a conformational change is induced by ligand binding. 
• Conformational change can be transmitted to a neighbouring subunit. 
• Intermediate conformations are possible. 
• Subunits can be in different conformations and change sequentially, so the mechanism is called a sequential model. 
• The allosteric activator works in the same way as S but by binding to a different site. The inhibitor works by preventing the transition from T to R that is induced by S binding.

4.0Model For Haemoglobin

• Cooperativity in Hb has features of both Symmetry (MWC) and Sequential (KNF)models. 
• Deoxy-Hb has a low affinity for oxygen. 
• The heme groups of the ß subunits are inaccessible to oxygen. 
• First, oxygen binds to an α subunit. 
• Small changes in the tertiary structure of the other α subunit increase its affinity for oxygen 3-fold(KNF model) 
• Hb with two oxygens bound is in equilibrium with a form of the protein in which all four subunits are in the R state. 
• This is equivalent to the T/R transition in the MWC model. 

5.0Sigmoid Curve Of Allosteric Enzyme

6.0Allosteric Inhibition 

• Heterotropic Inhibition: The effector may be different from the substrate; in this case, the effector is said to be a heterotropic effector 
• For example: feedback mechanisms.

7.0Feedback Inhibition

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