What is irreversible inhibition

The key difference between reversible and irreversible inhibition is that the reversible inhibition is a type of enzyme inhibition in which dissociation of the inhibitor from the enzyme-inhibitor complex is possible due to non-covalent binding. On the other hand, irreversible inhibition is a type of enzyme inhibition in which dissociation of the inhibitor from the enzyme-inhibitor complex is not possible due to covalent binding.

Enzymes are proteins that act as biological catalysts in our body. They increase the rate of reactions. Substrates bind with the active sites of the enzymes and transform into products. However, enzymes are specific for the substrates. Enzyme action can be regulated or inhibited by certain inhibitors. There are two types of enzyme inhibition processes; namely, they re the reversible inhibition and irreversible inhibition. In reversible inhibition, the inhibitor binds with the enzyme non-covalently while in the irreversible inhibition, the inhibitor binds with the enzyme either by covalently or non-covalently. These two processes differ from each other, and this article intends to discuss the difference between reversible and irreversible inhibition in detail.

CONTENTS

1. Overview and Key Difference
2. What is Reversible Inhibition
3. What is Irreversible Inhibition
4. Similarities Between Reversible and Irreversible Inhibition
5. Side by Side Comparison – Reversible vs Irreversible Inhibition in Tabular Form
6. Summary

What is Reversible Inhibition?

In reversible inhibition, the inhibitor inactivates the enzyme by binding non-covalently with it. Hence, the reversible inhibition is not a strong interaction between the enzyme and the inhibitor. Thus, by increasing the concentration of the substrate, this can be easily reversed, and it is possible to reactivate the enzyme easily. Moreover, there are two main types of reversible inhibition processes; namely, they are competitive inhibition and non-competitive inhibition.

In competitive inhibition, inhibitor resembles the substrate, and it competes with the substrate for the active site of the enzyme. Once the inhibitor occupies the active site, the substrate cannot bind with the enzyme, and the reaction does not occur. However, when the substrate concentration is high, competitive inhibition can be prevented.

Figure 01: Reversible inhibition

On the other hand, in non-competitive inhibition, inhibitor does not resemble the substrate. Hence, it does not compete with the substrate for the active site binding. It binds at a different place of the enzyme (allosteric site) and changes the three-dimensional structure of the enzyme. When the three-dimensional structure of the enzyme changes, its activity reduces. Hence, the reaction occurs at a slower rate or it does not occur.

What is Irreversible Inhibition?

Irreversible inhibition is the second type of enzyme inhibition, in which the inhibitor binds with the enzyme by a strong covalent bond and inhibits the enzyme activity. Hence, it is difficult to unbind the inhibitor from the enzyme. Therefore, it is not possible to reverse the reaction. Irreversible inhibitors often contain reactive functional groups. Thus, they can bind with the amino acid chains of the enzyme and form covalent bonds.

Figure 02: Irreversible Inhibition

Furthermore, irreversible inhibitors are specific. Hence, they do not bind with all proteins. Some examples of the irreversible inhibitors are penicillin, aspirin, diisopropylfluorophosphate, etc. There are three types of irreversible inhibitors; namely, they are the group-specific reagents, substrate analogues, and suicide inhibitors.

What are the Similarities Between Reversible and Irreversible Inhibition?

  • Reversible and irreversible inhibition are two types of enzyme inhibition pathways.
  • In both cases, the inhibitor binds with the enzyme.
  • Also, both can change the catalytic activity of the enzyme.

What is the Difference Between Reversible and Irreversible Inhibition?

Reversible inhibition and irreversible inhibition are two types of enzyme inhibition pathways. The key difference between reversible and irreversible inhibition is that it is possible to reverse reversible inhibition while it is not possible to reverse the irreversible inhibition. Furthermore, in reversible inhibition, the inhibitor binds with the enzyme by the weak non-covalent interaction while in the irreversible inhibition, the inhibitor binds with the enzyme by a strong covalent bond. Therefore, the dissociation of the enzyme-inhibitor complex is rapid in reversible inhibition while the dissociation of the enzyme-inhibitor complex is slow and hard in irreversible inhibition. Thus, it is another difference between reversible and irreversible inhibition.

Moreover, in reversible inhibition, when the inhibitor removes, the enzyme starts to work again while in the irreversible inhibition, the enzyme does not start to work again even though the inhibitor leaves the enzyme. Hence, this is also a difference between reversible and irreversible inhibition. Also, there are two main types of reversible inhibition namely competitive inhibition and non-competitive inhibition while there are three types of irreversible inhibition namely group-specific reagents, substrate analogues, and suicide inhibitors.

Below is an infographic on the difference between reversible and irreversible inhibition.

Summary – Reversible vs Irreversible Inhibition

Enzyme inhibition can be either reversible or irreversible. In summarizing the difference between reversible and irreversible inhibition; in reversible inhibition, the inhibitor binds with the enzyme non-covalently. Hence, the unbinding of the inhibitor from the enzyme is easy and rapid. On the other hand, in irreversible inhibition, the inhibitor binds with the enzyme covalently. Therefore, the inhibitor strongly binds with the enzyme and the dissociation of the enzyme-inhibitor complex is slow and hard. Therefore, this is the key difference between reversible and irreversible inhibition. Furthermore, in reversible inhibition, the reaction can be reversed, and the enzyme can be reactivated again. But in irreversible inhibition, the reaction cannot be reversed, and the enzyme cannot be activated again.

Reference:

1. “Enzyme Inhibitor.” Wikipedia, Wikimedia Foundation, 1 Jan. 2019. Available here  
2. “Enzyme Inhibitor.” NeuroImage, Academic Press. Available here   

Image Courtesy:

1.”DHFR methotrexate inhibitor”By Thomas Shafee – Own work, (CC BY 4.0) via Commons Wikimedia  
2.”Covalent-drugs-silence-proteins”By Dr. Juswinder Singh  (CC BY-SA 3.0) via Commons Wikimedia  

Filed Under: Bacteriology