List five enzymes and its five drugs. For competitive inhibition.
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I have excellent textbook data for the core five enzyme-drug pairs. Here is the complete, well-sourced answer:
Five Enzymes and Their Competitive Inhibitor Drugs
Competitive inhibitors bind directly to the enzyme's active site, structurally resembling the natural substrate. They increase apparent Km without changing Vmax, and their effect is reversible by increasing substrate concentration.
1. HMG-CoA Reductase
Natural substrate: HMG-CoA (hydroxymethylglutaryl coenzyme A)
Role: Rate-limiting step in cholesterol biosynthesis
| Drug | Class | Notes |
|---|---|---|
| Atorvastatin | Statin | Most prescribed statin globally |
| Rosuvastatin | Statin | High-potency, long half-life |
| Pravastatin | Statin | Hydrophilic; fewer drug interactions |
| Simvastatin | Statin | Prodrug, activated in liver |
| Fluvastatin | Statin | First fully synthetic statin |
Statins are structural analogs of HMG-CoA and compete effectively for the enzyme's active site, reducing de novo cholesterol synthesis. - Biochemistry, 8th ed Lippincott Illustrated Reviews, p. 189-190; Harper's Illustrated Biochemistry 32e
2. Dihydrofolate Reductase (DHFR)
Natural substrate: Dihydrofolate (DHF)
Role: Reduces DHF to tetrahydrofolate (THF), essential for purine and thymidylate synthesis
| Drug | Clinical Use | Notes |
|---|---|---|
| Methotrexate | Cancer, RA, psoriasis | Folate analog; most classic DHFR competitive inhibitor |
| Trimethoprim | Antibacterial | Selective for bacterial DHFR |
| Pyrimethamine | Antimalarial/toxoplasmosis | Selective for protozoal DHFR |
| Pemetrexed | Lung cancer | Multi-target antifolate |
| Pralatrexate | T-cell lymphoma | High-affinity DHFR inhibitor |
Methotrexate competes with DHF for binding at DHFR's active site, starving cells of THF and blocking nucleotide synthesis. - Goodman & Gilman's, p. (enzyme target section); Biochemistry, 8th ed Lippincott, p. 828
3. Angiotensin-Converting Enzyme (ACE)
Natural substrate: Angiotensin I
Role: Cleaves angiotensin I to the potent vasoconstrictor angiotensin II; also inactivates bradykinin
| Drug | Notes |
|---|---|
| Captopril | First ACE inhibitor; contains sulfhydryl group |
| Enalapril | Prodrug (enalaprilat is active form) |
| Lisinopril | Not a prodrug; directly active |
| Ramipril | Long-acting; used post-MI |
| Perindopril | High tissue ACE affinity |
ACE inhibitors are competitive inhibitors of ACE, causing vasodilation and blood pressure reduction. - Biochemistry, 8th ed Lippincott, p. 192; Henry's Clinical Diagnosis and Management by Laboratory Methods
4. Cyclooxygenase (COX-1 / COX-2)
Natural substrate: Arachidonic acid
Role: Converts arachidonic acid to prostaglandins and thromboxane; mediates inflammation and pain
| Drug | COX Selectivity | Notes |
|---|---|---|
| Ibuprofen | COX-1 and COX-2 | Reversible competitive inhibitor |
| Naproxen | COX-1 and COX-2 | Reversible; long-acting |
| Celecoxib | COX-2 selective | Reduced GI side effects |
| Rofecoxib (Vioxx) | COX-2 selective | Withdrawn due to cardiovascular risk |
| Diclofenac | Slight COX-2 preference | Also inhibits lipoxygenase |
Note: Aspirin is an irreversible inhibitor of COX (not a competitive inhibitor). Ibuprofen and other NSAIDs are the competitive inhibitors. - Basic Medical Biochemistry - A Clinical Approach, 6e
5. Dihydropteroate Synthase (DHPS)
Natural substrate: Para-aminobenzoic acid (PABA)
Role: Bacterial enzyme that incorporates PABA into dihydropteroate (step in folate synthesis); absent in humans
| Drug | Notes |
|---|---|
| Sulfamethoxazole | Most widely used; combined with trimethoprim (co-trimoxazole) |
| Sulfadiazine | Used in toxoplasmosis (with pyrimethamine) |
| Sulfadoxine | Long-acting; used in malaria |
| Sulfasalazine | Used in IBD and RA |
| Dapsone | Used in leprosy and PCP prophylaxis |
Sulfonamides are PABA analogs that competitively inhibit DHPS, blocking bacterial folate synthesis. This is a classic textbook example of competitive inhibition with a structural analog. - Goodman & Gilman's, enzyme inhibitor section
Key Mechanism Summary
| Feature | Competitive Inhibition |
|---|---|
| Binding site | Active site (same as substrate) |
| Structural relationship | Inhibitor is a substrate analog |
| Effect on Km | Increases (apparent) |
| Effect on Vmax | Unchanged |
| Reversibility | Usually reversible |
| Overcomeable by substrate | Yes |
Pharmacological note: Competitive inhibition is the most common mechanism exploited in drug design because targeting the active site with a structural analog allows high selectivity for a specific enzyme, and the reversibility allows dose titration.
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