Eicosanoids are a family of powerful lipid-derived signaling molecules that function as local chemical messengers throughout the body. They are named for the 20-carbon structure of the fatty acid precursors from which they are made. Unlike hormones, which travel through the bloodstream, eicosanoids act primarily near the site of their creation, influencing neighboring cells. These molecules are not stored but are rapidly synthesized on demand when a cell receives a stimulus, such as an injury or infection. They are quickly broken down and deactivated, ensuring their effects are transient and localized.
The Building Blocks: Fatty Acid Precursors
Eicosanoids originate from specific polyunsaturated fatty acids (PUFAs) embedded within cell membranes. Enzymes must first cleave these fatty acids from the membrane before they can be converted into signaling molecules. The precursors are derived from the Omega-6 and Omega-3 groups of dietary fats.
Arachidonic Acid (AA) is the primary Omega-6 precursor and is typically converted into eicosanoids that promote inflammation. Conversely, Omega-3 fatty acids, such as Eicosapentaenoic Acid (EPA), yield molecules that are often anti-inflammatory or less potent. The balance between these two dietary families influences the body’s overall inflammatory status.
Omega-3 EPA and Omega-6 AA compete for the same enzymatic pathways during synthesis. When EPA is utilized, it leads to the creation of molecules with inflammation-resolving effects. This biochemical competition explains why dietary intake of Omega-3 fatty acids is associated with a reduced risk of inflammatory diseases.
How Eicosanoids Are Made
The transformation of precursor fatty acids into active eicosanoids occurs via specialized enzymatic pathways inside the cell. The initial step involves phospholipase A2, which releases the fatty acid, such as arachidonic acid, from the cell membrane. The free fatty acid is then channeled into one of two major enzyme pathways.
The Cyclooxygenase (COX) pathway creates prostaglandins and thromboxanes, collectively known as prostanoids. This pathway involves two distinct forms of the enzyme, COX-1 and COX-2, which catalyze the initial conversion of the fatty acid into an unstable intermediate. This intermediate is then processed by other enzymes to yield the final, biologically active prostanoids.
The second major route is the Lipoxygenase (LOX) pathway, which synthesizes leukotrienes. This pathway utilizes enzymes like 5-lipoxygenase (5-LOX) to oxygenate the fatty acid. Leukotrienes are produced primarily in immune cells and are potent mediators in allergic and inflammatory conditions.
Primary Functions in the Body
Eicosanoids orchestrate the body’s immediate responses to injury, playing roles in inflammation, vascular tone, and blood clotting. Their diverse effects depend on the specific eicosanoid produced and the cell type it acts upon. The localized nature of this signaling allows for precise control over physiological processes.
Prostaglandins are significant mediators of inflammation and pain, particularly Prostaglandin E2 (PGE2). PGE2 sensitizes nerve endings to pain, contributes to fever, and causes blood vessel dilation, leading to the redness and swelling of inflammation. Leukotrienes, generated by white blood cells, are potent inflammatory agents that promote airway constriction and attract immune cells to the site of injury.
Eicosanoids regulate blood flow and vascular tone. Prostacyclin, produced by the lining of blood vessels, acts as a vasodilator, relaxing vessel walls and lowering blood pressure. This is balanced by thromboxane A2 (TXA2), a vasoconstrictor that causes blood vessels to narrow.
The balance between prostacyclin and TXA2 is essential for hemostasis, the process of stopping bleeding. TXA2 is released by platelets and promotes platelet aggregation, forming a clot at the site of injury. Prostacyclin acts as a counter-signal, inhibiting aggregation in healthy areas to ensure unrestricted blood flow.
Targeting Eicosanoids with Medication
Many common drugs target the eicosanoid system. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as aspirin and ibuprofen, block Cyclooxygenase (COX) enzymes. This reduces the production of inflammatory eicosanoids, decreasing the prostaglandins responsible for pain, fever, and swelling.
NSAIDs are classified based on their preference for the two COX enzyme forms. COX-1 is constitutively active and performs housekeeping tasks, producing prostaglandins that protect the stomach lining and thromboxane for normal platelet function. COX-2 is primarily induced at sites of inflammation.
Non-selective NSAIDs inhibit both COX-1 and COX-2, effectively reducing inflammation but causing side effects like stomach irritation and increased bleeding risk. Selective COX-2 inhibitors were developed to target only the inducible enzyme, aiming to reduce inflammation while sparing COX-1’s protective functions. However, some selective COX-2 inhibitors have been associated with cardiovascular risks due to an imbalance in the prostacyclin to thromboxane ratio.