Arachidonic acid metabolism pathway ()

Arachidonic acid metabolism pathway Overview

The Arachidonic acid metabolism pathway, also known as the inflammatory mediator biosynthesis pathway, focuses on the production of potent lipid mediators like prostaglandins and leukotrienes from arachidonic acid released from membrane phospholipids by cPLA2. It involves two main branches: the Cyclooxygenase (COX) pathway, producing prostaglandins, prostacyclins, and thromboxanes via COX-1 and COX-2 enzymes, and the Lipoxygenase (LOX) pathway, producing leukotrienes (LTB4 and cysteinyl leukotrienes) via enzymes like 5-lipoxygenase and FLAP. These mediators act through specific G protein-coupled receptors (e.g., prostaglandin receptors, BLT receptors, CysLT receptors) to mediate diverse biological functions, including inflammation, pain, fever, chemotaxis, and smooth muscle contraction. The pathway is a significant therapeutic target for inflammatory diseases, cancer, and tuberculosis, with drugs like NSAIDs, coxibs, and leukotriene modifiers acting at various points within the pathway. Emerging research also highlights the role of specialized pro-resolving mediators derived from omega-3 fatty acids within this broader lipid mediator landscape.

Mechanism of Action

The pathway is targeted at various enzymatic steps or receptor interactions. NSAIDs and coxibs inhibit COX enzymes to block prostaglandin synthesis. Leukotriene modifiers target 5-lipoxygenase or leukotriene receptors. FLAP inhibitors block the synthesis of leukotrienes by inhibiting 5-LOX activating protein. Other targets include specific synthases or inactivating enzymes like PTGR1.

Biological Functions

Safety Considerations

Interacting Drugs