Eicosanoids

Question 1

Eicosanoid

Answer 1

• 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!

Question 2

Types of eicosanoids

Answer 2

3 major classes
- Prostaglandins (PGs)
- Thromboxanes (Txs)
- Leukotrienes (LTs)

Question 3

Receptor and concentration level of both hormones and Eicosanoids

Answer 3

Both induce profound physiological effects at very low concentrations

Both bind to G-protein coupled receptors to initiate a signal transduction cascade (cAMP)

Question 4

How are Eicosanoids transported?

Answer 4

They are not transported in the blood (hormones are). They will be produced near their site of action.

Question 5

Where are eicosanoids produced?

Answer 5

Produced in all mammalian organ cells except RBCs.

Question 6

Stability of Eicosanoids

Answer 6

• Very unstable
• Rapidly degraded
• Promotes local and cell specific actions (therefore eicosanoids are produced at the site they are needed)

Question 7

Why can’t animals make omega-3 and omega-6?

Answer 7

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

Question 8

Where are omega-3 and omega-6 stored?

Answer 8

Stored in cells as a phospholipid, important for cell membranes

Question 9

What kind of eicosanoids do each of the omegas make?

Answer 9

Omega-3 makes eicosanoids with anti-inflammatory response

Omega-6 makes eicosanoids with pro- inflammatory

Question 10

Why are omega-6 often lower in supplements?

Answer 10

Lower because they produce pro-inflammatory eicosanoids.

Question 11

Formation of omega-3

Answer 11

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

Question 12

Formation of omega-6

Answer 12

Linoleic acid –> Arachindonic acid (AA)
–> used to produce different forms of eicosanoids: prostaglandins, thromboxanes, leukotrienes

Question 13

Omega-3/6 in Cats

Answer 13

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

Question 14

Eicosanoid synthesis

Answer 14

1. Omega 3/6 are stored as phospholipids in cell membranes
2. Phospholipase A2 is activated by increased Calcium concentration, physical trauma, immunoglobulins, microbial products, and cleaves the backbone to form AA, EPA, DHA.
3. Leads to 2 pathways: prostanoids and lekotrienes. Cyclooxygenase will produce prostanoids. Lipooxygenase will produce leukotrienes

Question 15

What inhibits eicosanoid synthesis?

Answer 15

Inhibited by anti-inflammatory signals (glucocorticoids)

Question 16

Prostanoid production

Answer 16

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

Question 17

Different functions of prostaglandins

Answer 17

Control muscle function (vessel constriction and dilation), regulate CNS activity (pain reception), mediate cytokine production for inflammation response

Question 18

Leukotrienes production

Answer 18

Formed by Lipooxygenase (LO) in leukocytes. Leukotrienes transport out of leukocytes through transporter, and bind to receptors on tissues acting as inflammatory mediators

Question 19

Leukotrienes Function

Answer 19

Biological responses: pro-inflammatory action, bronchoconstriction, mucus secretion, edema in airways

Question 20

Leukotrienes and asthma

Answer 20

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

Question 21

NSAIDs

Answer 21

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)

Question 22

COX-2 specific inhibitors

Answer 22

• 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

Question 23

Thromboxanes

Answer 23

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)