Eicosanoids

Question 0

How is arachadonic acid released from the membrane?

Answer 0

Phospholipase A2 (found in pancreatic juices and in many cells)

Question 1

What membrane lipid is necessary for eicosanoid synthesis?

Answer 1

Arachadonic acid

Question 2

What dietary FAs are eicosanoid precursors?

Answer 2

Linoleic acid and alpha Linolenic acid

Question 3

What other membrane lipids are cleaved by phospholipase A2?

Answer 3

PIP2!

Question 4

What is the mechanism of cortisol?

Answer 4

Inhibits phospholipase A2

Question 5

What is the rate limiting step of the synthesis of prostaglandins and thromboxanes?

Answer 5

Cyclooxygenase

Question 6

What is the rate limiting step in the synthesis if leukotrienes?

Answer 6

5-lipoxygenase (LOX)

Question 7

Name the common intermediate between PGs and THs

Answer 7

PGH2

Question 8

What drugs act at the COX step?

Answer 8

Aspirin (irreversibly) and NSAIDs INHIBIT BOTH COX1 AND COX2

Question 9

Describe COX1

Answer 9

Constitutive (found in almost all cell types) normal physiological functions like gastric protection maintenance of renal blood flow and vascular homeostasis

Question 10

Describe COX2

Answer 10

Non constitutive (only in liver and macrophages) in response to immune and inflammatory mediators.
Leads to pain heat redness swellin fever
Inhibited by glucocorticoids

Question 11

What promotes clotting?

Answer 11

Thromboxane A2 (TXA2)

Question 12

What inhibits clotting?

Answer 12

Prostacyclin PGI2

Question 13

How does aspirin work?

Answer 13

Irreversibly acetylates a serine residue of COX. Inhibits formation of both TXA2 and PGI2. PGI2 is made in Endothelium; therefore more can be made to replace the inhibited. TXA2 is made in RBCs which can’t make protein. Therefore low does aspirin results in a high PGI2/TXA2; less clotting

Question 14

How do selective cox2 inhibitors increase risk of clots?

Answer 14

Platelets only have COX1; TXA2 isn’t inhibited. Prostaglandin is inhibited in endothelial cells which have both

Question 15

How does fish oil in the diet affect inflammation?

Answer 15

Eicosapentaenoic acid is incorporated into human membranes and used instead of arachadonic acid. TXA3 is less potent , PGI3 is te same leads to less clotting

Question 16

Which leukotrienes are involve in allergy and hyper sensitivity?

Answer 16

LTC4-F4

Question 17

Which leukotrienes are chemo attractants?

Answer 17

LTB4

Question 18

What is the common leukotriene intermediate?

Answer 18

LTA4

Question 19

What do leukotrienes LTC4-F4 have in common?

Answer 19

All have a cysteine residue (cysteinyl-leukotrienes) part of slow reacting substance of anaphylaxis. Very powerful. Increase vascular permeability,, bronchoconstriction vasoconstriction lung edema

Question 20

What are the components of asthma?

Answer 20

Airflow obstruction
Increased mucus
Bronchoconstriction
Infiltration of inflammatory cells in airway wall

Question 21

What targets of drugs can be used to treat asthma? (3 targets)

Answer 21

1) release of arachadonic acid (corticosteroids)
2) LOX Inhibitors
3) cysteinyl-leukotriene receptor antagonists

Question 22

What is the function of 5-HPETE?

Answer 22

Intermediate in the formation of leukotrienes from arachadonic acid.

Question 23

What is the action of PGF2alpha?

Answer 23

Vasoconstriction