Eicosanoids Flashcards
Eicosanoid
- Modified 20 carbon polyunsaturated fatty acids
- Synthesized from dietary fatty acids (Omega-3 and Omega-6)
- Mediate several processes: inflammatory response, production of pain and fever, regulation of blood pressure, induction of blood clot, induction of labor, and more!
Types of eicosanoids
3 major classes
- Prostaglandins (PGs)
- Thromboxanes (Txs)
- Leukotrienes (LTs)
Receptor and concentration level of both hormones and Eicosanoids
Both induce profound physiological effects at very low concentrations
Both bind to G-protein coupled receptors to initiate a signal transduction cascade (cAMP)
How are Eicosanoids transported?
They are not transported in the blood (hormones are). They will be produced near their site of action.
Where are eicosanoids produced?
Produced in all mammalian organ cells except RBCs.
Stability of Eicosanoids
- Very unstable
- Rapidly degraded
- Promotes local and cell specific actions (therefore eicosanoids are produced at the site they are needed)
Why can’t animals make omega-3 and omega-6?
Animals are missing desaturases that form double bonds past the 9th carbon.
Must get from diet (plant seed - flaxseed, or fish oil). Fish are high in omega-3 because of their ingestion of microalgae
Where are omega-3 and omega-6 stored?
Stored in cells as a phospholipid, important for cell membranes
What kind of eicosanoids do each of the omegas make?
Omega-3 makes eicosanoids with anti-inflammatory response
Omega-6 makes eicosanoids with pro- inflammatory
Why are omega-6 often lower in supplements?
Lower because they produce pro-inflammatory eicosanoids.
Formation of omega-3
Alpha-linolenic acid –> Eicosapentaenoic Acid (EPA) –> Docosahexaenoic Acid (DHA)
Both DHA and EPA are used to produce different forms of the 3 classes (Prostaglandins, Thromboxanes, Leukotrienes) of eicosanoids
Formation of omega-6
Linoleic acid –> Arachindonic acid (AA)
–> used to produce different forms of eicosanoids: prostaglandins, thromboxanes, leukotrienes
Omega-3/6 in Cats
Cats lack the delta-6 desaturase activity, so must obtain direct EPA, DHA, or AA from other animal organs or supplement
DO NOT GIVE linolenic acid or linoleic acid to cats
Eicosanoid synthesis
- Omega 3/6 are stored as phospholipids in cell membranes
- Phospholipase A2 is activated by increased Calcium concentration, physical trauma, immunoglobulins, microbial products, and cleaves the backbone to form AA, EPA, DHA.
- Leads to 2 pathways: prostanoids and lekotrienes. Cyclooxygenase will produce prostanoids. Lipooxygenase will produce leukotrienes
What inhibits eicosanoid synthesis?
Inhibited by anti-inflammatory signals (glucocorticoids)
Prostanoid production
Formed by Cyclooxygenase (COX-1 and COX-2)
- COX-1 is constitutively expressed. Enzyme generates the signal ligand for homeostatic intercellular signaling
- COX-2 is inducible by inflammation stimuli. Enzyme with increased activity accompanying acute and chronic inflammatory conditions
Different functions of prostaglandins
Control muscle function (vessel constriction and dilation), regulate CNS activity (pain reception), mediate cytokine production for inflammation response
Leukotrienes production
Formed by Lipooxygenase (LO) in leukocytes. Leukotrienes transport out of leukocytes through transporter, and bind to receptors on tissues acting as inflammatory mediators
Leukotrienes Function
Biological responses: pro-inflammatory action, bronchoconstriction, mucus secretion, edema in airways
Leukotrienes and asthma
Elevated leukotriene levels (chronic inflammation, allergies). Characterized by increased mucous production and bronchoconstriction (breathing and wheezing)
Ex. used to prevent harmful particles from getting into airways
Treatment: bronchodilator or corticosteroid
NSAIDs
Used to reduce pain, decrease fever, decrease inflammation, commonly used to treat prescribed arthritis
Inhibits both COX-1 and COX-2 pathway (so cannot be prescribed long term)
COX-2 specific inhibitors
- Developed to treat acute and chronic inflammations
- Medications have reduced side effects of GI bleeding and kidney necrosis as compared with NSAIDs
- Used to treat canine arthritis and tumors
- Not used in Humans as it has lead to ~40% increase in risk for cardiovascular complications
- Effective in reducing prostaglandins, but increase in ratio of thromboxane (Tx) that regulates clotting
Thromboxanes
Synthesized primarily in platelets (thrombocytes)
- Activated by damage to the arterial wall; induce platelet aggregation and vascular muscle constriction
- Under normal conditions: PGI2 and nitric oxide cause vasodilation to inhibit thromboxanes
- Without the vasodilation, there is an increase in vasoconstriction (which is why cardiovascular issues in humans)
