Competitive inhibition occurs when a molecule that is not the enzyme’s natural substrate attaches to the active site of the enzyme, preventing the natural substrate from binding and suppressing enzyme activity. To measure the inhibitor’s efficiency, the affinity of a competitive inhibitor for an enzyme’s active site is compared to the affinity of a natural substrate for the active site.
Competitive inhibitors like 5-fluorouracil and Sulfa medicines can be dangerous. Bacteria and protozoa metabolise 5-fluorouracil into their RNA, rendering the RNA incapable of producing proteins. As a result, protein synthesis is slowed. Sulfa medicines, on the other hand, prevent bacteria from producing folic acid by blocking dihydropteroate synthase. Bacteria die as a result of the lack of folic acid. Other competitive inhibitors, such as Gleevec or methotrexate, can be helpful by inhibiting enzymes involved in cancer cell proliferation (Bcr-Abl kinase and dihydrofolate reductase, respectively).
Competitive Inhibitor
A competitive inhibitor is any chemical that can bind to the active site of an enzyme with high enough affinity to compete with the enzyme’s natural substrate, lowering enzyme activity. A competitive inhibitor’s structure will be close enough to the enzyme’s natural substrate to allow it to bind to the active site, but structurally different enough that it cannot be catalysed to a new product by the enzyme, preventing the enzyme from producing products from its natural substrate. Competitive inhibitors have the disadvantage of being reversible. Enzyme activity will be restored if the inhibitor concentration is reduced sufficiently or the natural substrate concentration is increased sufficiently.
Inhibition of Competitive Enzymes
When a molecule, chemical, or medicine can attach to the active site of an enzyme to the point that the natural substrate must compete with the inhibitor for access to the enzyme for catalysis, this is known as competitive enzyme inhibition. Because the natural substrate must compete with the inhibitor, enzymes can digest natural substrates at a slower rate, inhibiting but not destroying the enzyme’s activity. Knowing the affinity of a competitive inhibitor and a natural substrate for an enzyme allows us to make preliminary estimations of the inhibitor concentration required to achieve the desired level of inhibition, whether it is lower or higher.
Methotrexate is an excellent example. Methotrexate inhibits Bcr-Abl kinase to such an extent in high concentrations that it is harmful to both malignant and non-cancerous cells. However, at lesser dosages, it inhibits Bcr-Abl kinase sufficiently to kill malignant cells while allowing the majority of non-cancerous cells to survive. Competitive inhibitors are appealing as pharmaceuticals and pesticides because of their ability to tune the concentration of competitive inhibitors so that the target enzyme functions at the desired rate (or to reverse them quickly by increasing natural substrate concentrations or decreasing inhibitor concentrations).
Mechanism of Competitive Enzyme Inhibition
Enzyme action is sometimes described as a “lock and key” mechanism, with the active site of the enzyme acting as the lock and the substrate acting as the key. When the substrate “key” unlocks the enzyme’s “lock,” the enzyme transforms the substrate into a new product in some fashion (or products). The product is released after modification, resetting the enzyme’s “lock.” After that, the lock will wait for a fresh substrate “key.” A competitive inhibitor functions like a defective key, fitting the lock but not being digested by the enzyme. When a competitive inhibitor interacts with an enzyme, the amino acid residues in the enzyme’s active site are hidden from the natural substrate, momentarily inhibiting the enzyme’s activity.
Examples of Competitive Inhibition
Competitive inhibitors come in a range of forms and are employed in a variety of applications, ranging from disease control and medicines to insecticides and bactericides.
A few examples of competitive inhibitor functions are shown below:
- To cure glaucoma, acetazolamide inhibits carbonic anhydrase.
- To treat erectile dysfunction, Viagra and Levitra suppress phosphodiesterases.
- To treat AIDS, the drugs nevirapine and efavirenz suppress HIV reverse transcriptase.
- In insects, organophosphates and carbamates inhibit acetylcholinesterase (insecticide)
Conclusion
We conclude that Competitive inhibition can be overcome by increasing the amount of substrate in the process, increasing the likelihood of the enzyme and substrate binding together. As a result, competitive inhibition only changes the Km but not the Vmax.