Enzyme inhibitors are molecules that reduce or prevent enzyme activity, and they can be classified into several types based on their mechanism of action. The primary types are competitive, uncompetitive, and noncompetitive inhibitors.
Types of Enzyme Inhibitors
Here's a breakdown of the different types of enzyme inhibitors:
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Competitive Inhibitors:
- Competitive inhibitors bind to the active site of the enzyme, preventing the substrate from binding.
- They compete directly with the substrate for the active site.
- The effect of a competitive inhibitor can be overcome by increasing the substrate concentration.
- Example: Malonate inhibits succinate dehydrogenase, an enzyme in the citric acid cycle, by competing with succinate.
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Uncompetitive Inhibitors:
- Uncompetitive inhibitors bind only to the enzyme-substrate complex.
- They do not bind to the free enzyme.
- Increasing the substrate concentration increases the inhibition, because it leads to more enzyme-substrate complex formation, which the inhibitor can then bind to.
- Example: Some herbicides act as uncompetitive inhibitors.
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Noncompetitive Inhibitors:
- Noncompetitive inhibitors bind to a site on the enzyme that is not the active site (an allosteric site).
- They can bind to either the free enzyme or the enzyme-substrate complex.
- Noncompetitive inhibitors change the shape of the enzyme, reducing its ability to bind to the substrate or catalyze the reaction effectively.
- Increasing the substrate concentration does not overcome the inhibition.
- Example: Heavy metals like lead (Pb) can act as noncompetitive inhibitors.
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Mixed Inhibitors:
- Mixed inhibitors are similar to noncompetitive inhibitors, but they have different affinities for the free enzyme and the enzyme-substrate complex.
- They bind at a site distinct from the active site.
- In mixed inhibition, if the inhibitor binds to the enzyme only, it increases the Km value and if it binds to the enzyme-substrate complex, it decreases the Km value.
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Irreversible Inhibitors:
- Irreversible inhibitors bind covalently to the enzyme, permanently inactivating it.
- These inhibitors often modify an amino acid residue in the active site, making the enzyme non-functional.
- Example: Nerve gases like diisopropyl fluorophosphate (DIFP) irreversibly inhibit acetylcholinesterase. Penicillin is also an irreversible inhibitor of transpeptidase, an enzyme bacteria use to build cell walls.
| Inhibitor Type | Binding Site | Effect on Vmax | Effect on Km | Can Inhibition Be Overcome by Increasing Substrate? |
|---|---|---|---|---|
| Competitive | Active Site | No Change | Increases | Yes |
| Uncompetitive | Enzyme-Substrate Complex | Decreases | Decreases | No |
| Noncompetitive | Allosteric Site | Decreases | No Change | No |
| Mixed | Allosteric Site | Decreases | Increases or Decreases | No |
Enzyme inhibitors play a crucial role in regulating metabolic pathways and are also important in the development of drugs and pesticides.
