Inhibition of enzymes: competitive, non-competitive, covalent, allosteric. Use of enzyme inhibitors in medicine.
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Types of Enzyme Inhibition[edit | edit source]
a. Competitive Inhibition[edit | edit source]
- [1]Mechanism:
- Inhibitor resembles the substrate and competes for binding at the active site.
- Can be overcome by increasing substrate concentration.
- Effect on Enzyme Kinetics:
- Increases Km (decreases substrate affinity), but Vmax remains unchanged.
- Examples:
- Methotrexate: Competitively inhibits dihydrofolate reductase (used in cancer therapy).
- Statins: Inhibit HMG-CoA reductase (used in cholesterol management).
b. Non-Competitive Inhibition[edit | edit source]
- Mechanism:
- Inhibitor binds to an allosteric site (different from the active site), affecting enzyme function without competing with the substrate.
- Cannot be overcome by increasing substrate concentration.
- Effect on Enzyme Kinetics:
- Reduces Vmax but does not change Km.
- Examples:
- Cyanide: Inhibits cytochrome c oxidase in the electron transport chain.
c. Covalent (Irreversible) Inhibition[edit | edit source]
- Mechanism:
- Inhibitor forms a stable, covalent bond with the enzyme, permanently inactivating it.
- Effect on Enzyme Kinetics:
- Permanently reduces enzyme activity.
- Examples:
- Aspirin: Acetylates and irreversibly inhibits cyclooxygenase (COX) enzymes (used as an anti-inflammatory).
- Penicillin: Irreversibly inhibits bacterial transpeptidase (used as an antibiotic).
d. Allosteric Inhibition[edit | edit source]
- Mechanism:
- Inhibitor binds to an allosteric site, causing a conformational change that reduces enzyme activity.
- Often involved in feedback regulation.
- Effect on Enzyme Kinetics:
- May alter Vmax, Km, or both, depending on the inhibitor.
- Examples:
- ATP inhibition of phosphofructokinase-1 (PFK-1) in glycolysis.
Use of Enzyme Inhibitors in Medicine[edit | edit source]
a. Therapeutic Applications[edit | edit source]
- Cancer Treatment: Methotrexate inhibits folate metabolism, blocking DNA synthesis in cancer cells.
- Cholesterol Reduction: Statins lower cholesterol by inhibiting HMG-CoA reductase.
- Pain and Inflammation:
- Aspirin and NSAIDs (e.g., ibuprofen) inhibit COX enzymes to reduce prostaglandin synthesis.
- Antibiotics: Penicillin inhibits bacterial cell wall synthesis.
- Antiviral Drugs:
- Protease inhibitors (e.g., lopinavir) block viral protein processing.
- Reverse transcriptase inhibitors (e.g., AZT) prevent viral replication in HIV.
b. Toxicological and Emergency Use[edit | edit source]
- Toxin Antidotes:
- Ethanol competes with methanol for alcohol dehydrogenase, preventing toxic formaldehyde production.
c. Diagnostic Tools[edit | edit source]
- Enzyme-linked assays: Enzyme inhibitors are used to regulate and quantify enzyme activity in diagnostic tests.
Summary Table of Inhibitor Types and Applications[edit | edit source]
| Type of Inhibition | Binding Site | Effect on Km | Effect on Vmax | Medical Applications |
|---|---|---|---|---|
| Competitive | Active site | Increases | No change | Methotrexate, Statins |
| Non-Competitive | Allosteric site | No change | Decreases | Cyanide |
| Covalent (Irreversible) | Active site | N/A | Permanently reduces | Aspirin, Penicillin |
| Allosteric | Allosteric site | Variable | Variable | ATP inhibition of PFK-1, Feedback loops |
- ↑ Nelson, D. L., Cox, M. M., & Lehninger, A. L. (2021). Lehninger Principles of Biochemistry (8th ed.). Macmillan Learning. Copeland, R. A. (2005). Evaluation of Enzyme Inhibitors in Drug Discovery: A Guide for Medicinal Chemists and Pharmacologists. Wiley-Interscience.
