Inhibition of Enzyme Action: Enzyme catalysts are often known as biocatalysts, change the rate of biochemical reactions without undergoing any change. In general, a natural enzyme is a biological macromolecule synthesised by living organisms. These are essentially complicated nitrogenous proteins that assist in the catalysis of metabolic activities in living organisms. Catalysts are required for all metabolic reactions in living organisms.

Enzyme inhibitors are molecules that attach to an enzyme’s active site and reduce the enzyme’s activity. These substances could be medications, pathogens, or insecticides. An enzyme inhibiting agent attacks the active site of an enzyme. This article will dive deep into the concept of inhibition of enzyme action, its definition, types and examples.

Enzyme Inhibitors

1. Enzymes are biological macromolecules, often known as biological catalysts, that increase the rate of biochemical reactions without changing the nature of the reactions.
2. It’s a highly selective catalyst that speeds up metabolic reactions while also increasing their specificity.
3. There are a variety of proteins capable of interfering with the activity of a single enzyme.
4. An inhibitor is a molecule that acts directly on an enzyme to reduce its catalytic rate.
5. Some enzyme inhibitors are natural body metabolites that stop an enzyme from working, while others are foreign substances like medications or toxins.

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Types of Inhibition of Enzyme Action

Enzyme inhibition may be of two main types:
1. Reversible Inhibition
a. Competitive reversible inhibition
b. Non-competitive reversible inhibition
c. Uncompetitive inhibition
2. Irreversible Inhibition
a. Allosteric Modulation or Feedback Inhibition

1. Reversible Inhibition

1. Reversible inhibition could be overcome by the removal of the inhibitor from the enzyme.
   2. A Lineweaver–Burk plot can be used to discriminate between competitive and non-competitive reversible enzyme inhibitors

A.  Competitive Inhibitors

Fig: Competitive Inhibition

1. Competitive inhibitors fight for the enzyme’s active site with the substrate, forming an enzyme-substrate complex.
2. A competitive inhibitor is often structurally identical to the enzyme’s normal substrate. As a result, it competes with substrate molecules for active site binding.
3. Because the enzyme can only bind one of two molecules: a substrate or an inhibitor, it can’t do both simultaneously; binding to the inhibitor reduces the enzyme’s activity.
4. The competitive inhibitor binds to the active site in a reversible manner.
5. Because a sufficiently high substrate concentration will successfully compete with the inhibitor molecule attaching to the active site, the activity of a competitive inhibitor is overcome at high substrate concentrations.
6. Many pharmaceuticals mimic the structure of a target enzyme’s substrate and function as competitive inhibitors of the enzyme.

B.  Non- competitive Inhibitors

Fig: Non-competitive Inhibition

1. Non-competitive inhibitors bind to the enzyme or the enzyme-substrate complex at a site other than the active site, lowering the enzyme’s activity.
2. A non-competitive inhibitor binds reversibly to a site other than the active site, causing a change in the enzyme’s overall three-dimensional structure and lowering catalytic activity.
3. The enzyme may bind the inhibitor, the substrate, or both the inhibitor and the substrate together since the inhibitor binds at a different site other than the substrate.
4. Because the effects of a non-competitive inhibitor can’t be countered by increasing the substrate concentration, Vmax declines.
5. The action of pepstatin on the enzyme renin is an example of non-competitive inhibition.

Particulars	Competitive	Non-competitive
Where does it act?	Active Site	Alternative site
Change of Km	Increase	Unchanged
Change of Vmax	Unchanged	Decrease

Fig: Diagram Shows the Effect of Enzyme Inhibitors on the Reaction Rate

C. Uncompetitive Inhibition

1. Uncompetitive inhibition is the inhibition of enzymatic activity caused by the inhibitor binding to an allosteric site, similar to non-competitive inhibition, but with the enzyme-substrate (ES) complex rather than the enzyme molecule.
2. The removal of an activated enzyme-substrate complex induces a decrease in the maximum velocity of the chemical reaction, which is the mechanism of uncompetitive inhibition.
3. Tetramethylene sulfoxide and \(3\)-butyl thiol ene oxide, for example, inhibit liver alcohol dehydrogenase in an uncompetitive manner.

2. Irreversible Inhibition

1. Irreversible inhibitors attach to the enzyme and turn it inactive.
2. Inhibitors that bind irreversibly to an enzyme frequently make a covalent linkage with an amino acid residue at or near the active site, inactivating the enzyme permanently.
3. Ser and Cys residues, which feature reactive \({\text{-OH}}\) and \({\text{-SH}}\) groups, are susceptible amino acid residues.

a.  Allosteric Modulation or Feedback Inhibition

Fig: Multiple Enzymes Catalyse a Succession of Reactions in Metabolic Pathways

End-product inhibition is a biological regulatory mechanism in which the end product of an enzyme inhibits its activity. In allosteric enzymes, it is a sort of reversible inhibition. The inhibitor is a non-competitive low molecular intermediate or product of a metabolic pathway with a sequence of events involving multiple enzymes. As a result, it’s also known as the end product or feedback inhibition. Modulators are another name for inhibitors. The modulator is a substance that binds to allosteric enzymes at a different location than the catalytic one yet has an effect on the latter, either blocking or activating it. The inhibition of the enzyme hexokinase (glucokinase) by glucose-\(6\)-phosphate, the result of the reaction catalysed by it, is an example of feedback or allosteric inhibition.

1. Feedback inhibition is another name for end-product inhibition.
2. This inhibition has a role in determining how much of the final product will be produced.
3. To produce the desired output, most biochemical processes are complex and require numerous enzymes. End-product inhibition acts on the process’s initial enzyme in such cases.
4. End-product inhibitors bind to the enzyme’s allosteric site, causing changes in the enzyme’s structure and modifying the active site.
5. The end product binds to the allosteric site in feedback inhibition, causing modifications in the enzyme.
6. End-product inhibition, for example, is seen in humans, where the presence of cholesterol in the blood inhibits the enzyme responsible for the liver’s cholesterol production.

Competitive Inhibition	Allosteric Inhibition
The inhibitor binds to the enzyme’s active site.	The inhibitor binds to a different part of the active site other than the active site.
It has no effect on the enzyme’s conformation.	The conformation of enzymes is changed.
An inhibitor covers the active site.	Conformation of the active site is changed so that substrate cannot combine with it.
The inhibitor’s board structure is similar to that of the substrate.	The inhibitor and the substrate have no structural similarities.
The metabolic pathway catalysed by the enzyme does not connect to the inhibitor.	The inhibitor is a byproduct or intermediary of the enzyme’s metabolic process.
It doesn’t have any regulatory function.	Allosteric inhibition has a regulatory effect in that it prevents a product from forming in excess.

Phosphorylation

Phosphorylation provides another mechanism by which enzymes can be inhibited. This is usually accomplished by the action of kinase enzymes, which, depending on the situation, can either block or activate an enzyme. Kinase enzymes cut a phosphate group off ATP and bind it to themselves. A cascade reaction occurs when this causes a rise in enzyme activity, allowing a huge response to be generated from a little stimulus.

Examples of Enzyme Inhibition

Enzyme inhibitors can be used in a range of settings, including medicine and agriculture (as pesticides)

1. The neuraminidase inhibitor, Relenza TM, is one example of a competitive inhibitor’s application in the treatment of influenza.
2. The usage of cyanide as a poison is an example of a non-competitive inhibitor in action (prevents aerobic respiration)

Summary

Enzymes can be controlled in ways that increase or decrease their activity. There are a variety of substances that can inhibit or increase enzyme action and a variety of ways of doing so. When an inhibitor molecule is similar enough to a substrate in some enzyme inhibition, it can bind to the active site and simply prevent the substrate from binding. Because an inhibitor molecule competes with the substrate for active site binding, the enzyme is inhibited by competitive inhibition. Non-competitive inhibition, on the other hand, occurs when an inhibitor molecule binds to the enzyme at a position other than an allosteric site while still blocking substrate binding to the active site.

Frequently Asked Questions (FAQs)

Q.1. What is inhibition in an enzyme?
Ans: A decrease in enzyme-related processes, enzyme production, or enzyme activity is called enzyme inhibition.

 Q.2. What is an enzyme inhibitor?
Ans: Enzyme inhibitors bind to the enzyme and cause it to lose activity without causing damage to the enzyme’s protein structure.

Q.3. How does inhibition affect enzyme activity?
Ans: Inhibitors lower the compatibility of substrate and enzyme by attaching to their active sites, preventing the formation of Enzyme-Substrate complexes, stopping the catalysis of processes, and reducing (at times to zero) the amount of product produced by a reaction.

Q.4. What are the two types of enzyme inhibition?
Ans: There are two types of inhibitors; competitive and non-competitive inhibitors. Competitive inhibitors bind to the active site of the enzyme and prevent the substrate from binding.

Q.5. Which types of drugs act by inhibiting an enzyme in the body?
Ans: Among the many types of drugs that act as enzyme inhibitors, the following may be included: antibiotics, acetylcholinesterase agents, certain antidepressants such as monoamine oxidase inhibitors and some diuretics.

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