Eicosanoids and COX Enzymes Overview

Eicosanoids, Prostaglandins, Thromboxanes, Leukotrienes

• Eicosanoids are polyunsaturated fatty acids produced in tissues. They are highly bioactive and mediate inflammation and redness.
• Prostanoids are a type of eicosanoid including prostaglandins, thromboxane, and prostacyclin.
• Arachidonic Acid (AA) is the main starting material for eicosanoid synthesis. It's found in cell membranes.
• Phospholipase A2 removes AA from cell membranes.
• AA is then enzymatically converted into various products. These include epoxyeicosatrienoic acids (EETs), leukotrienes, lipoxins, prostaglandins, prostacyclin, and thromboxane.
• These products are produced by enzymes like Lipoxygenase (LOX) and Cyclooxygenase (COX).

COX Enzymes

• COX-1 is found in most cells and produces prostanoids vital for bodily functions, including protecting the stomach lining and kidneys.
• COX-2 is an inducible enzyme, meaning its production is triggered by stimuli (stress, cytokines, tissue injury) and results in the production of prostanoids that cause inflammation.
• Non-steroidal anti-inflammatory drugs (NSAIDs), like aspirin and ibuprofen, inhibit COX enzymes, thus reducing inflammation.

Products of COX Enzymes

• Prostaglandins are involved in various functions, including uterine contractions during childbirth, blood flow regulation, and influencing blood clotting.
• Thromboxanes promote platelet aggregation (blood clotting).
• Prostacyclin prevents platelet aggregation.

Prostaglandins as Drugs

• Alprostadil is a PGE1 used for smooth muscle relaxation and treatment of impotence.
• Misoprostol is a PGE1 derivative used to prevent peptic ulcers. Dinoprostone is another PGE analog used for uterine contractions.

Lipoxygenase (LOX) Products

• Leukotrienes are LOX products mainly found in white blood cells.
• Leukotrienes are important mediators of inflammation (e.g., in asthma).

Biological Effects of Prostaglandins and Thromboxanes

• Prostaglandins and thromboxanes (TXs) affect various tissues. They can cause vasoconstriction (narrowing of blood vessels) and vasodilation (widening of blood vessels).
• Prostaglandins and TXs are involved in smooth muscle contraction and relaxation in the gastrointestinal tract and airways.
• TXA is a potent vasoconstrictor.
• PGs promote vasodilation.

Inhibition of Eicosanoid Synthesis

• Corticosteroids are the gold standard for inhibiting eicosanoid synthesis, largely by inhibiting phospholipase enzymes.
• NSAIDs like ibuprofen and indomethacin inhibit COX enzymes, preventing prostaglandin production.

Dietary Manipulation of Arachidonic Acid (AA)

• Linoleic acid, found in sunflower and corn oils, can act as a substitute for AA. However, the eicosanoids produced aren't identical.
• Cold-water fish oils contain omega-3 fatty acids which can also affect eicosanoid production.

Other Notes

• Aspirin inhibits platelet aggregation by inhibiting PG synthesis.
• Kidney function relies on prostaglandins for various processes, and decreased PG production can negatively affect kidney health.
• Prostaglandins play critical roles in the central nervous system (CNS), including fever responses and neurotransmitter release.
• Eicosanoids are linked with inflammation, bone remodeling, and various other physiological responses.