Eicosanoids – Synthesis, Regulation & Functions

Vocabulary flashcards covering precursors, enzymes, pathways, mediators, regulation, and clinical aspects of eicosanoid biology.

Eicosanoids

20-carbon oxygenated fatty-acid derivatives that act as local hormones; include prostaglandins, thromboxanes, leukotrienes, lipoxins, resolvins, isoprostanes.

Arachidonic Acid (AA)

Major ω-6 polyunsaturated fatty acid precursor of most eicosanoids; released from membrane phospholipids by PLA₂.

Linoleic Acid

Essential ω-6 fatty acid converted to arachidonic acid via elongase and desaturase enzymes.

Eicosapentaenoic Acid (EPA)

ω-3 fatty acid precursor of anti-inflammatory eicosanoids and resolvins.

Docosahexaenoic Acid (DHA)

ω-3 fatty acid used by aspirin-modified COX-2 to form anti-inflammatory resolvins.

ω-6 / ω-3 Ratio

Proportion of dietary ω-6 to ω-3 fatty acids; ratios >4:1 increase risk of chronic inflammatory diseases.

Phospholipase A₂ (PLA₂)

Enzyme activated by stress signals that releases AA from membrane phospholipids; inhibited by steroids.

Cyclo-oxygenase-1 (COX-1)

Constitutive enzyme that converts AA to PGH₂ for tissue-specific prostaglandins and thromboxanes; irreversibly inhibited by aspirin.

Cyclo-oxygenase-2 (COX-2)

Inducible enzyme involved in inflammation; substrate specificity altered by aspirin to produce resolvins and epi-lipoxins.

Lipoxygenases (LOX-5, LOX-12/10, LOX-15)

Enzyme family that oxygenates AA to produce leukotrienes (5-LOX) and lipoxins (5- & 15-LOX).

Prostaglandin H₂ (PGH₂)

Central intermediate produced by COX enzymes; precursor for diverse prostaglandins and thromboxanes.

Prostacyclin (PGI₂)

Antithrombotic prostaglandin made by vascular endothelium; causes vasodilation and inhibits platelet aggregation.

Thromboxane A₂ (TXA₂)

Pro-thrombotic eicosanoid synthesized by platelets; promotes vasoconstriction and platelet aggregation.

Prostaglandin E₂ (PGE₂)

Anti-inflammatory prostaglandin that elevates cAMP, dilates vessels, and suppresses immune cell activity.

Prostaglandin D₂ (PGD₂)

Vasodilatory, anti-aggregatory prostaglandin involved in allergy and sleep regulation.

Prostaglandin F₂α (PGF₂α)

Pro-inflammatory prostaglandin causing vasoconstriction, bronchoconstriction, and smooth-muscle contraction.

Leukotrienes

LOX-derived eicosanoids; mediate bronchoconstriction, leukocyte chemotaxis, and vascular permeability.

Cysteinyl Leukotrienes (LTC₄, LTD₄, LTE₄)

Leukotrienes containing cysteine; potent bronchoconstrictors central to asthma pathology.

Lipoxins (LXA₄, LXB₄)

AA-derived molecules generated via 5- and 15-LOX; promote resolution of inflammation.

Epi-Lipoxins

Aspirin-triggered lipoxins formed via modified COX-2 plus 5-LOX; have anti-inflammatory, anti-cancer effects.

Resolvins

Anti-inflammatory mediators produced from EPA/DHA by aspirin-altered COX-2 in leukocytes and endothelium.

Isoprostanes

Non-enzymatic peroxidation products of AA; released by PLA₂ and serve as biomarkers of oxidative stress.

Anandamide

Endogenous analgesic lipid neurotransmitter acting on cannabinoid receptors; generated by transacylase and released by PLD.

Platelet-Endothelial Balance

Endothelium-derived PGI₂ opposes platelet TXA₂ to regulate clotting and vascular tone.

NSAIDs

Non-steroidal anti-inflammatory drugs that reversibly inhibit COX-1/2 (e.g., ibuprofen) or selectively COX-2 (e.g., acetaminophen).

Aspirin

Irreversible COX-1 inhibitor that reduces TXA₂, lowers heart-attack risk, and shifts COX-2 to produce anti-inflammatory resolvins/lipoxins.

Smoking & PGP

Cigarette smoke inhibits degradation of pro-inflammatory chemoattractant PGP, sustaining lung inflammation.

Chronic Inflammation Risks

High ω-6 / ω-3 ratio promotes diseases such as cancer, CVD, rheumatoid arthritis, Alzheimer’s, and accelerated aging.

Eicosanoid Homeostasis

Balanced production of diverse eicosanoids maintains gastric mucosa, vascular tone, immunity, and inflammation resolution.

Transacylase-PLD Pathway

Nonclassical route for anandamide synthesis involving phospholipid transacylase followed by phospholipase D.

5-LOX Activation

Converts AA to leukotriene A₄; prevalent in immune cells, driving bronchoconstriction and vascular permeability.

PGH₂ Tissue Specificity

Different tissues convert PGH₂ to unique products: vascular endothelium→PGI₂; platelets→TXA₂.

Heart-Attack Prevention by Aspirin

Permanent COX-1 blockade in platelets decreases TXA₂, lowering clot formation and thereby reducing myocardial infarction and stroke risk.