Dla 9: Eicosanoids

Question 1

Describe eicosanoid

1) Synthesis
2) General structure
3) Precursors

Answer 1

1) Synthesis:
- Membrane phospholipid cleaved using phopholipase A2 –> Arachdonic acid (20C’s) –> acted on by Cycloogenase (to form Prostanoids) or lipooxygenase (to form Leuotrienes)

2) General structure:
- Glycerol backbone
- Saturated fatty acid
- Unsaturated fatty acid
- Phosphate Nitrogen base

3) Precursors
Arachidonic acid:
-20C w 4 DB (Omega 6)
-Can be made from Linoleic acid
-Makes PGI2 and TXA2
-Series 2 prostanoids

Eicosapentaenoic acid:

• 20 C w 5 DB (Omega 3)
• Can be made from Linolenic acid
• Series 3 prostanoids
• PGI3 and TXA3

Question 2

Compare and contrast the 2-series of polyunsaturated fatty acids to the 3-series

What are their effects on vascular health (TXA2 vs TXA3)

Answer 2

2-series and 3-series of polyunsaturated fatty acids:
-Increasing Omega 3’s will increase TXA3 –> less likely for thrombosis

TXA2:
-More potent for platelet aggregation

TXA3:
-less potent than TXA2 for platelet aggregation

Question 3

Discuss the role of leukotrienes
(also cysteinyl leukotrienes) in asthma
and in anaphylactic shock

Answer 3

• Released by mast cells (activation Phopholipase A2) w allergic reaction, releases histamine –> pathway begins to make Cysteinyl leukotrienes
• Cysteinyl leukotrienes (LTC4, LTD4, LTE4)
• Mediate allergic and anaphylactic response (Hives from vasodilation), swelling, itchiness

• Cause Bronchoconstriction (asthma) and airway obstruction
(need Lipoxygenase inhibitors)

Question 4

What are the types of Prostanoids how they are synthesized or activated, and their role?

Answer 4

Prostaglandins:

1) PGE2
- Activated by macrophages
- Mediator of inflammation
- Vasodilation (redness)

2) PGF2-Alpha
- Synthesize by uterine tissue
- Facilitates induction of labor

3) PGI2
- Synthesize by endothelium
- Stops platelet aggregation
- Vasodilator
- Increases formation of cAMP in platelets

Thromboxane:

4) TXA2
- Activated by platelets
- Facilitates aggregation (clot)
- Vasoconstriction

Question 5

Inhibitors of Eicosanoids

Answer 5

1) Aspirin, NSAID
- Inhibit COX I and II

2) Cortisol
- Inhibits release phospholipase which inhibits formation of arachidonic acid –> prostaglandins or leukotrienes = anti-inflammatory and anti-allergic agent
- Inhibits COX-II

3) Coxib
- Selective Cox-3 Inhibitor

3) Lipoxygenase Inhibitors:
- Reduce formation of leukotrienes;
- Used as anti-allergic agents (management of asthma)

Question 6

What happens when a low dose of Aspirin is taken?

Answer 6

Aspirin irreversible inhibitor of COX

• Inhibits platelet COX –> less TXA2 synthesis
• Endothelium can make new enzyme –> PGI2 synthesis not affected
• PGI2&raquo_space; TXA2 inhibits platelet aggregation (Used as anti-thrombogenic agent)

-LESS CLOTTING