Lecture 5 : EICOSANOIDS

Question 1

What are the members of the Eicosanoid family

Answer 1

1. Prostaglandins
2. Prostacyclins
3. Thromboxanes
4. Leukotrienes
5. Lipoxins
6. Hydroxy & Epoxy Eicosaenoic Acids
7. Levuglandins

Question 2

Eicosanoids are how many carbons?

Answer 2

20 carbons

Question 3

What is eicosanoids dervied from?

Answer 3

Prostanoic Acid

Question 4

What are the minor prostanoic acids?

Answer 4

PGA
PGD

Question 5

What are the major protanoic acids

Answer 5

PGE
PGFalpha

Question 6

What prostanoic acids are cyclic endoperxoide

Answer 6

PGG
PGH–> intermediates of eicosanoids

Question 7

What prostanoic acid is prostacyclin

Answer 7

PGI

Question 8

TXA2 are

Answer 8

class of eicosanoids

Question 9

Eicosanoids are not stored or stored?

Answer 9

Not stored (no storage forms)

Question 10

We do not store eicosanoids but we do store

Answer 10

precursor of eicosanoids: **polyunsaturated fatty acids **

Question 11

Series one precrusor and then product

Answer 11

Eicosatrienoic acid
PGE1

Question 12

Series two fatty acid precursor and product

Answer 12

Arachidonic acid
PGE2

Question 13

Series 3 f.a. precursor and product

Answer 13

Eicospentaenoic acid
PGE3

Question 14

What is 20:4

Answer 14

Arachondic acid

Question 15

Explain the reaction that release the arachidonic acid

Answer 15

• Synthsis is on depand by stimuli
• phosphaticlyclinositol which has 20:4 on position 2
• Use phospholipase A2-> RLS (in cytosol to membtane and begin cleavage)
• Creates lysophosphatidylinositol and frees 20:4 to create eicosanoids

Question 16

We get linolate from diet to create_

Answer 16

arachidonic acid

Question 17

What is the enzyme in membrane phospholipid that cleaves arachidonic acid

Answer 17

Phopholipase A2

Question 18

the arachidonic acid can go down two pathways:

Answer 18

lipzygenase and cyclooxygenase

Question 19

What causes the specific eicosanoids to be created

Answer 19

It depends what is the is surplus of enzymes in those tissues
(ex. increase of PGE synthase–> PGE2)

Question 20

With the cyclooxygenase has two isomers:
What does it create?

Answer 20

Cox 1
Cox 2
all eicosanoids besides leukotrienes

Question 21

What is the functions for cox-1 and cox-2?

Answer 21

Cox-1: responsible for sythsis of ecosanoids basal cellular activity-> house keeping to maintain cell
Cox-2: induceble cyclooxygenase that is responsible for inflammatory response

Question 22

What can inhibit phospholipase A2

Answer 22

• glucocorticoids because it inhibits mRNA of cox 2 so no inflammation

Question 23

Aspirin is called

Answer 23

acetylsallcylate acid
NSAIDs

Question 24

What does aspirin due?

Answer 24

• The NSAIDs covalently modify serine residue active site of cyclooxygenase so it makes the cycloozygenase inactive (irreversible rxn)
• The archidonic acid cannot get to site for eicosanoid rxn

Question 25

How does cox1 and cox 2 differ with aspirin?

Answer 25

* **Cox 1 is more sensitive** to inhibition by aspirin than Cox 2 * Difference in active site

Question 26

What is platelets rich in and what is endothelium rich in?

Answer 26

* platelets rich in cox-1 * Endothelium rich in cox-2

Question 27

What are the effects of aspirin (platelet vs endothelum)

Answer 27

* Platelet -> Arachidonic acid-> PGG2/PGH2 -> thromboxane which is potent in platelet activators and vasoconstritors (aggrate +constrict) * Endothelium->Arachidonic acid-> PGG2/PGH2-> prostacyclin which inhibits platelet aggration and vasodialation * HOMOSTATSIS

Question 28

When heart patients have to take aspirin everyday, they can get bloody ulcers so what was the solution

Answer 28

1/2 cox1 and 1/2 cox2

Question 29

Aspirin inhibits more cox 1 or cox 2

Answer 29

cox 1

Question 30

When you have selective COX-2 inhibitors, what happens?

Answer 30

**Prostacyclin levels drops** and all the arachidonic acid is shifted to **thromboxane (increase levels)** so vasoconstrication and platelets aggrate -> DIE

Question 31

We must homostatsis of _ and _ for vascular health

Answer 31

TXA2 and PGI2

Question 32

Fish oils have high amounts of what? and what does that make?

Answer 32

Eicopentanoic acid (series 3) so it makes TXA3 (not constrictor or aggrator) and PGI3 (vasodilator)

Question 33

What is the ratio of TXA2 and TXA3 in someone that takes fish oil vits

Answer 33

TXA2 decrease TXA3 increase

Question 34

Inuits diets are high in marine fishes and high in eicosanoids. They have healther vascular systems and longer clotting factors. Why?

Answer 34

Has increase of Txa3 (not vasoconstrictor nor aggrator) because fish has increase amounts of eicosaPENTAenoic acid instead of Txt2 (vasoconstrictor nor aggrator)

Question 35

Explain what happens in normal everyday of prostacyclins and thromboxyanes in platelets and blood vessel walls

Answer 35

Platelets are rich in thombaoxane (vasoconstrictor) so the body shifts PGH2 (before thombaoxane) from the platelet to blood vessel (rich in prostatcylin sythetase) to make prostcyclin (vasodialator)

Question 36

Explain what happens in injury to blood vassel of prostacyclins and thromboxyanes in platelets and blood vessel walls

Answer 36

In platelet TxA2 is shifted to blood vessel wall to help clot and not bleed out

Question 37

What does 5-lipoxygenase synthesize

Answer 37

leukotrienes which is active component of SRS-A (Slow-reacting substance of anaphylaxis)

Question 38

Patient comes in, dr gives two aspirin then a couple of hours later the patient has difficulty breathing, what happened?

Answer 38

Aspirin **inhibits the cyclooxygenase pathway** but not the lipoxygenase pathway. Since the arch acid has no where to go, it all goes **down lipoxygenase pathway and causes aspirin induced ashma**. This is becasue lipoxygenase cause a sustained contraction of the smooth m. of bronchi