Cyclooxygenase-1 (COX-1)
Cyclooxygenase-1 (COX-1) is an enzyme responsible for the conversion of arachidonic acid into prostaglandins, which play a key role in maintaining physiological homeostasis.
Key Functions of COX-1
- Gastrointestinal Protection
- Produces prostaglandins (PGE₂, PGI₂) that protect the gastric mucosa by increasing mucus and bicarbonate secretion, reducing acid secretion, and promoting mucosal blood flow.
- COX-1 inhibition can lead to gastric ulcers and bleeding (a major side effect of NSAIDs).
- Platelet Aggregation (Blood Clotting)
- Produces thromboxane A₂ (TXA₂) in platelets, which promotes platelet aggregation and vasoconstriction.
- Aspirin irreversibly inhibits COX-1, reducing thromboxane formation, preventing blood clots (used in cardiovascular disease prevention).
- Renal Function
- Helps regulate renal blood flow and sodium excretion.
- COX-1 inhibitors may reduce renal perfusion, leading to kidney damage, especially in patients with compromised kidney function.
- Vascular Homeostasis
- Helps maintain blood vessel integrity and regulates vascular tone.
COX-1 vs. COX-2: Key Differences
| Feature | COX-1 | COX-2 |
|---|---|---|
| Expression | Constitutive (always present in most tissues) | Inducible (expressed during inflammation, except in kidneys and brain) |
| Function | Homeostatic (stomach lining, kidney function, platelet aggregation) | Inflammatory response (pain, fever, swelling) |
| Inhibition Effects | Increased GI toxicity, reduced platelet aggregation, possible kidney effects | Anti-inflammatory, analgesic, and antipyretic effects |
| Selective Inhibitors | Aspirin (low dose) | Celecoxib, Rofecoxib (withdrawn due to cardiovascular risks) |
Clinical Relevance
- NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) like aspirin, ibuprofen, and naproxen inhibit COX enzymes to reduce pain and inflammation.
- COX-1 inhibition (especially with non-selective NSAIDs) is associated with an increased risk of gastric ulcers and bleeding.
- COX-2 selective inhibitors (e.g., celecoxib) were developed to minimize GI side effects while maintaining anti-inflammatory effects.