Difference between reversible and irreversible enzyme inhibition

The main difference between reversible and irreversible enzyme inhibition is that reversible enzyme inhibition inactivates enzymes through non-covalent interactions. In contrast, irreversible enzyme inhibition inactivates enzymes through covalent inactivation of the active site . Furthermore, the inhibiting effect in the case of the reversible enzyme inhibition is reversible, but the inhibiting effect in the irreversible enzyme inhibition is irreversible.  

In short, reversible and irreversible enzyme inhibition are the two methods ofenzyme inhibition mechanisms that are responsible for reducing enzyme activity. In general, inhibitors reduce the compatibility of substrate and enzyme, which leads to the inhibition of the formation of enzyme-substrate complexes.  

Key areas covered  

1. What is reversible enzyme inhibition - definition, process, types 2. What is irreversible enzyme inhibition - definition, process, types 3. What are the similarities between reversible and irreversible enzyme inhibition - overview of the similarities 4. What is the difference between reversible and irreversible enzyme inhibition - comparison of the main differences

key terms  

Competitive inhibitors , covalent, irreversible enzyme inhibition, non-competitive inhibitors , non-covalent, reversible enzyme inhibition, non-competitive inhibitors Difference between reversible and irreversible enzyme inhibition - summary of the comparison

What is reversible enzyme inhibition?  

Reversible enzyme inhibition is a type of enzyme inhibition in which inhibitor molecules bind to the enzyme through non-covalent interactions. Here these interactions include hydrogen bonds , hydrophobic interactions,   and ionic bonds . However, reversible inhibitor molecules do not undergo chemical reactions with the amino acid residues of the active site of the enzyme. Therefore, reversible inhibitors can be removed from the enzyme either by dilution or dialysis.

Difference between reversible and irreversible enzyme inhibition

Figure 1: Competitive Inhibition - DHFR Methotrexate Inhibitor

In addition, the four types of reversible enzyme inhibitors are competitive, non-competitive, non-competitive, and mixed inhibitors. Of these, competitive inhibitors are the compounds structurally similar to the substrate of a particular enzyme. It therefore competes with the substrate for the active site of the enzyme, reducing the enzymatic effect. In contrast, non-competitive inhibitors bind to the enzyme or the enzyme-substrate complex at a location other than the active site. However, this can change the 3D conformation of the enzyme, which in turn reduces enzyme function.

Difference between reversible and irreversible enzyme inhibition

Figure 2: Types of reversible enzyme inhibition

In the meantime , non-competitive inhibitors bind to the enzyme-substrate complex, effectively eliminating the enzyme-substrate complex and thus reducing product formation. On the other hand, mixed inhibitors can bind both to enzyme and to enzyme-substrate complex and release the substrate from the enzyme-substrate-inhibitor complex which is formed. In contrast to the mixed inhibitors, non-competitive inhibitors allow the substrate to dissociate from the enzyme-substrate-inhibitor complex that is being formed.  

What is irreversible enzyme inhibition?  

The irreversible enzyme inhibition is the second type of enzyme inhibition with a permanent inhibitory effect. The essential essential feature of the irreversible enzyme inhibitors is also that they bind covalently to the amino acid residues of the active center of the enzyme. For this reason , this type of inhibitor carries reactive functional groups such as nitrogen mustards , aldehydes, haloalkanes, alkenes, Michael acceptors, phenylsulfonates or fluorophosphonates. Significantly, these reactive groups are nucleophilic and form covalent adducts with the amino acid side chains in the active center.

Mainly between - reversible vs. irreversible enzyme inhibition

Figure 3: Reaction of the irreversible inhibitor diisopropyl fluorophosphate (DFP) with a serine protease

For example , nerve gases, in particular DIFP, irreversibly inhibit biological systems by forming an enzyme-inhibitor complex. Usually it happens through a specific OH group of serine on the active centers of certain enzymes. Typically, peptidases such as trypsin and chymotrypsin contain serine groups at the active site that can be inhibited by DIFP. Consequently, this type of covalent modification of the active site of the enzyme can lead to permanent inactivation of the enzyme, and the enzymatic effect is difficult to regain by the addition of excess substrate to the medium.  

Similarities Between Reversible and Irreversible Enzyme Inhibition  

  • Reversible and irreversible enzyme inhibition are two types of enzyme inhibition mechanisms.  
  • They are responsible for reducing the activity of the enzyme.  
  • Usually they reduce the compatibility of the enzyme with its substrate and inhibit the formation of the enzyme-substrate complex.  
  • During inhibition, inhibitor molecules bind to the enzyme either temporarily or permanently.  
  • Of course, enzyme inhibition helps regulate metabolism. In addition, many drug molecules are enzyme inhibitors.  

Difference between reversible and irreversible enzyme inhibition  

definition  

Reversible enzyme inhibition refers to the process of binding inhibitors to the enzyme through noncovalent interactions so that once they are removed they allow enzyme function to be restored. Irreversible enzyme interaction is the process of binding inhibitors to the enzyme through covalent interactions, so that their dissociation takes a long time and the enzyme action is permanently suspended.  

Type of inhibitor binding  

In the case of reversible enzyme inhibition, inhibitors bind via non-covalent interactions such as hydrogen bonds , hydrophobic interactions,   and ionic bonds. In contrast, in irreversible enzyme inhibition, inhibitors bind through covalent interactions that modify amino acid residues through reactive functional groups.  

Dissociation of the enzyme-inhibitor complex  

In the case of reversible enzyme inhibition, the enzyme-inhibitor complex dissociates rapidly, while in the case of irreversible enzyme inhibition, the enzyme-inhibitor complex dissociates very slowly.  

Restoration of inhibition  

Reversible enzyme inhibition can be re-established, but re-establishment of irreversible enzyme inhibition takes a long time.  

Types  

Four types of reversible enzyme inhibition are competitive, non-competitive, non-competitive and mixed inhibition, while irreversible enzyme inhibition occurs through the covalent inactivation of the active site of the enzyme.  

Examples of inhibitors  

Some of the examples of reversible enzyme inhibitors include DHFR, antiviral drugs such as ritonavir, oseltamivir and tipranavir, etc. Meanwhile, some of the examples of irreversible enzyme inhibitors include DFP, DFMO, insecticides   like malathion , herbicides   like glyphosate and disinfectants   like triclosan etc.   

diploma  

Reversible enzyme inhibition is the process of temporarily inhibiting the action of an enzyme. Therefore, the function of the enzyme can be restored by releasing the inhibitory effect. Reversible inhibitors also bind to the enzyme via non-covalent interactions. Therefore, it allows the enzyme-inhibitor complex to dissociate rapidly, thereby restoring enzyme function. In contrast, irreversible enzyme inhibition is the process of permanent inhibition of enzyme function. Therefore, the enzyme-inhibitor complex takes a long time to dissociate. In addition, inhibitor molecules bind covalently to the remnants of the active center of the enzyme and thus block the formation of the enzyme-substrate complex. For these reasons, the main difference between reversible and irreversible enzyme inhibition is the binding mechanism of the inhibitors to the enzyme and the resulting effects.  

References:

1. "18.8 Enzyme Inhibition." The Basics of General, Organic and Biological Chemistry, vol. 1.0. Available here .

Image courtesy:

1. “DHFR Methotrexate Inhibitor” By Thomas Shafee - Own work ( CC BY 4.0 ) via Commons Wikimedia 2. “Types of inhibition de” By fullofstars - de: Image: Inhibition.png (PD) (Public Domain) via Commons Wikimedia 3 “DIF Response” By TimVickers - Own work (Public Domain) via Commons Wikimedia

About the author: Lakna

Lakna, a graduate in molecular biology and biochemistry, is a molecular biologist and has a broad and strong interest in discovering things related to nature