cycloossigenasi

Cycloossigenasi, also known as cyclooxygenase (COX), is an enzyme that catalyzes the first committed step in the biosynthesis of prostanoids. It converts arachidonic acid, released from membrane phospholipids, into prostaglandin G2 (PGG2) and then prostaglandin H2 (PGH2), which are precursors to prostaglandins, prostacyclins, and thromboxanes.

There are two main isoforms in humans: COX-1 and COX-2. COX-1 is constitutively expressed in many tissues and participates in homeostatic functions such as protecting the gastric mucosa, supporting renal perfusion, and regulating platelet aggregation. COX-2 is inducible and upregulated by inflammatory cytokines, growth factors, and endotoxins; it is largely responsible for the production of inflammatory prostaglandins.

Biochemically, COX enzymes are homodimers located in the cytosol or associated membranes. They possess two catalytic activities within a single protein: cyclooxygenase (oxygenation of arachidonic acid) and a peroxidase step that reduces PGH2 to various prostanoids. The active site is accessible by a hydrophobic channel in which arachidonic acid binds.

Pharmacology and clinical relevance: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX enzymes, reducing prostanoid synthesis. Aspirin acetylates the active site and irreversibly inhibits COX-1 and COX-2. COX-2 selective inhibitors were developed to minimize gastrointestinal toxicity but have been associated with cardiovascular risks. Prostaglandins and thromboxanes regulate inflammation, pain, fever, vascular tone, and hemostasis; dysregulation is implicated in arthritis, cancer, and cardiovascular disease.

Regulation and genetics: COX expression is regulated at transcriptional and post-transcriptional levels by cytokines, hormones, and cellular stress. Inhibiting COX activity can affect mucosal protection, renal function, and hemostasis, underscoring the balance between therapeutic benefit and adverse effects in clinical use.