Cyclooxygenase (COX)

Cyclooxygenase Overview

Cyclooxygenase (COX), also known as prostaglandin G/H synthase (EC 1.14.99.1), is an enzyme critical for prostaglandin biosynthesis from arachidonic acid. It has two main isoforms: COX-1 (constitutive) and COX-2 (inducible). Both enzymes have cyclooxygenase and peroxidase activities, converting arachidonic acid to prostaglandin H2 via a complex radical mechanism involving a heme group. COX-1 is expressed in many tissues and is involved in maintaining physiological functions like protecting the stomach lining and regulating platelet aggregation. COX-2 is primarily induced during inflammatory processes and is involved in inflammation, pain, and fever. It is also upregulated in many tumors. Cyclooxygenases are major targets for nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. NSAIDs inhibit COX enzymes, reducing prostaglandin production to alleviate symptoms. Traditional NSAIDs inhibit both isoforms, leading to potential gastrointestinal side effects due to COX-1 inhibition. COX-2 selective inhibitors aim to reduce these side effects while maintaining anti-inflammatory effects. COX-1 inhibition by aspirin is leveraged for its anti-platelet effects to reduce cardiac events. Understanding the distinct roles of COX-1 and COX-2 is crucial for developing drugs with improved efficacy and safety profiles.

Mechanism of Action

Cyclooxygenase enzymes are inhibited by drugs like NSAIDs. This inhibition reduces the production of prostaglandins, which are mediators of pain, inflammation, and fever. Inhibition of COX-1 also reduces thromboxane A2 production, affecting platelet aggregation, and reduces prostaglandins that protect the stomach lining. COX-2 selective inhibitors primarily target the inducible COX-2 isoform.

Biological Functions

Safety Considerations

Interacting Drugs