Arachidonic Acid and Cyclooxygenase Pathway

Arachidonic Acid and Inflammation

• Arachidonic acid is a 20-carbon fatty acid with 4 double bonds.
• It is involved in the cycloxygenase pathway and enzymatic pathways.
• Enzymatic pathways include COX-1 and COX-2, which produce prostaglandins.

COX-1 and COX-2

• COX-1 is always expressed and protects the gastric mucosa.
• COX-2 is induced by injury and is involved in inflammation.
• NSAIDS (non-steroidal anti-inflammatory drugs) block both COX-1 and COX-2, but can cause gastric problems.
• Blocking COX-2 reduces inflammation and is beneficial for patients with high levels of PGE2.

Prostaglandins

• Prostaglandins are products of arachidonic acid and have various functions, including:
  • Vasodilation and inhibition of platelet aggregation (PGI2).
  • Pro-inflammatory effects (PGE2).
  • Abortion (PGE2).
  • Receptors for prostaglandins act on different targets, such as thrombosis and vasodilation.

Omega-3 Fatty Acids

• Omega-3 fatty acids reduce the formation of prostaglandins and leukotrienes.
• They give rise to 3-series prostaglandins, which are less potent than the 2-series.

Leukotrienes

• Leukotrienes are formed from arachidonic acid through the 5-lipoxygenase pathway.
• They have pro-inflammatory effects, including:
  • Vasoconstriction.
  • Increased permeability.
  • Chemotaxis.
• Zileuton inhibits 5-lipoxygenase, reducing the formation of leukotrienes.

Inhibition of Inflammation

• Inhibiting the release of arachidonic acid from phospholipids can reduce inflammation.
• Blocking the action of phospholipase A2 can prevent the formation of prostaglandins and leukotrienes.