Lecture 5 : EICOSANOIDS Flashcards
What are the members of the Eicosanoid family
- Prostaglandins
- Prostacyclins
- Thromboxanes
- Leukotrienes
- Lipoxins
- Hydroxy & Epoxy Eicosaenoic Acids
- Levuglandins
Eicosanoids are how many carbons?
20 carbons
What is eicosanoids dervied from?
Prostanoic Acid
What are the minor prostanoic acids?
PGA
PGD
What are the major protanoic acids
PGE
PGFalpha
What prostanoic acids are cyclic endoperxoide
PGG
PGH–> intermediates of eicosanoids
What prostanoic acid is prostacyclin
PGI
TXA2 are
class of eicosanoids
Eicosanoids are not stored or stored?
Not stored (no storage forms)
We do not store eicosanoids but we do store
precursor of eicosanoids: **polyunsaturated fatty acids **
Series one precrusor and then product
Eicosatrienoic acid
PGE1
Series two fatty acid precursor and product
Arachidonic acid
PGE2
Series 3 f.a. precursor and product
Eicospentaenoic acid
PGE3
What is 20:4
Arachondic acid
Explain the reaction that release the arachidonic acid
- 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
We get linolate from diet to create_
arachidonic acid
What is the enzyme in membrane phospholipid that cleaves arachidonic acid
Phopholipase A2
the arachidonic acid can go down two pathways:
lipzygenase and cyclooxygenase
What causes the specific eicosanoids to be created
It depends what is the is surplus of enzymes in those tissues
(ex. increase of PGE synthase–> PGE2)
With the cyclooxygenase has two isomers:
What does it create?
Cox 1
Cox 2
all eicosanoids besides leukotrienes
What is the functions for cox-1 and cox-2?
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
What can inhibit phospholipase A2
- glucocorticoids because it inhibits mRNA of cox 2 so no inflammation
Aspirin is called
acetylsallcylate acid
NSAIDs
What does aspirin due?
- 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
How does cox1 and cox 2 differ with aspirin?
- Cox 1 is more sensitive to inhibition by aspirin than Cox 2
- Difference in active site
What is platelets rich in and what is endothelium rich in?
- platelets rich in cox-1
- Endothelium rich in cox-2
What are the effects of aspirin (platelet vs endothelum)
- 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
When heart patients have to take aspirin everyday, they can get bloody ulcers so what was the solution
1/2 cox1 and 1/2 cox2
Aspirin inhibits more cox 1 or cox 2
cox 1
When you have selective COX-2 inhibitors, what happens?
Prostacyclin levels drops and all the arachidonic acid is shifted to thromboxane (increase levels) so vasoconstrication and platelets aggrate -> DIE
We must homostatsis of _ and _ for vascular health
TXA2 and PGI2
Fish oils have high amounts of what? and what does that make?
Eicopentanoic acid (series 3) so it makes TXA3 (not constrictor or aggrator) and PGI3 (vasodilator)
What is the ratio of TXA2 and TXA3 in someone that takes fish oil vits
TXA2 decrease
TXA3 increase
Inuits diets are high in marine fishes and high in eicosanoids. They have healther vascular systems and longer clotting factors. Why?
Has increase of Txa3 (not vasoconstrictor nor aggrator) because fish has increase amounts of eicosaPENTAenoic acid instead of Txt2 (vasoconstrictor nor aggrator)
Explain what happens in normal everyday of prostacyclins and thromboxyanes in platelets and blood vessel walls
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)
Explain what happens in injury to blood vassel of prostacyclins and thromboxyanes in platelets and blood vessel walls
In platelet TxA2 is shifted to blood vessel wall to help clot and not bleed out
What does 5-lipoxygenase synthesize
leukotrienes which is active component of SRS-A (Slow-reacting substance of anaphylaxis)
Patient comes in, dr gives two aspirin then a couple of hours later the patient has difficulty breathing, what happened?
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
