Eicosanoids

Question 1

Eicosanoids are important bio-active agents synthesized form what?

Answer 1

PUFAs - 20 carbons long

Question 2

Prostanoids are synthesized by the ___ pathway

Answer 2

cyclooxygenase (COX)

Question 3

The leukotrienes and lipoxins are synthesized by the ____ pathway

Answer 3

lipoxygenase

Question 4

Both the COX pathway and the lipoxygenase pathway start with a 20 carbon PUFA, usually ____ acid

Answer 4

arachidonic

Question 5

The arachidonic acid is derived from membrane ____. It is released by the action of ____ ___

Answer 5

phospholipid; phospholipase A2

Question 6

What is the rate-limiting step in prostaglandin synthesis?

Answer 6

hydrolysis of arachidonic acid

Question 7

Agents which stimulate the production of prostaglandins do so by stimulating the activity of what?

Answer 7

phospholipase A2

Question 8

The other C20 PUFAs may serve as precursors. EPA (C20:5) is obtained from what? It is a w-__ acid

Answer 8

diet; 3

Question 9

PGH2 is the first prostaglandin product and is the common intermediate of what?

Answer 9

1. the other important prostaglandins

2. the thromboxanes

Question 10

Prostaglandin synthase (PGS) has two components: cylclooxygenase (COX) and PG hydroperoxidase. What do these two components catalyze?

Answer 10

1. COX: catalyzes synthesis of PGG2

2. PG hydroperoxidase catalyzes the formation of PGH2 from PGG2

Question 11

PG hydroperoxidase requires what?

Answer 11

GSH

Question 12

The number of double bonds in the side chains depends on the PUFA precursor. IF the precursor is eicosatrienoic acid, the product would be ____. If the precursor is eicosapentaenoic acid, the product would be ___.

Answer 12

PGH1; PGH3

Question 13

There are two forms of COX. COX1 is a ____ enzyme found where?

Answer 13

constitutive; found in gastric mucosa, platelets, vascular endothelium and kidney

Question 14

There are two forms of COX. COX2 is a ___ enzyme found where?

Answer 14

inducible; found in activated macrophages and monocytes which have been stimulated by PAF, IL-1, or LPS; also found in smooth muscle cells, epithelial cells and neurons

Question 15

COX2 induction is inhibited by ____

Answer 15

glucocorticoids

Question 16

The ____ inhibit COX.

ex: aspirin, ibuprofen etc.

Answer 16

NSAIDS

Question 17

Aspirin inhibits COX__ more than COX__

Answer 17

2; 1

Question 18

Aspirin’s mechanism of action involves ___ of the COX enzyme

Answer 18

acetylation

Question 19

Steroid anti-inflammatory drugs (hydrocortisone, prednisone) act by inhibiting this enzyme’s activity.

Answer 19

phospholipase A2

Question 20

PGE2 and PGF2 are major prostaglandins produced where?

Answer 20

kidney and spleen

Question 21

PGE2 is produced by what?

Answer 21

macrophages, mast cells, and B cells

Question 22

PGD2 is produced by ___ cells

Answer 22

mast

Question 23

PGI2 and PGF2 are major prostaglandins produced by ___ ___

Answer 23

blood vessels

note: PGI2 is an important inhibitor of platelet aggregation

Question 24

Thromboxane A2 (TXA2) is a major prostaglandin produced by ____

Answer 24

platelets

note: stimulates platelet aggregation

Question 25

The half-life of TXA2 is very long. True or false?

Answer 25

False; very short - it is rapidly converted to the inactive TXB2

Question 26

In what 3 ways do prostaglandins mediate inflammation?

Answer 26

1. induce redness and heat
2. increase capillary permeability
3. pyrogens activate synthesis of prostaglandins

Question 27

Prostaglandins stimulate ____ contraction and inhibit ____ acid secretion

Answer 27

uterine; gastric

Question 28

HPETEs are highly reactive intermediates that are rapidly converted to their analogous _____ acids or to ____

Answer 28

HETEs; leukotrienes

Question 29

The most important products of lipoxygenases in humans is ____-____ since these are converted into the leukotrienes

Answer 29

5-HPETE

Question 30

Leukotrienes are important secretory products of ____ and each one contains a conjugated ___ group

Answer 30

leukocytes; trienoic

note: the subscript number refers to the total number of double bonds

Question 31

Leukotrienes mediate ____ disorders

Answer 31

inflammatory

Question 32

SRS-A is a mixture of LTC4, LTD4, and LTE4 and is a potent stimulator of the ___ ___ musculature

Answer 32

bronchial airway

Question 33

LTB4, LTC4, LTD4, and LTE4 increase ___ ___

Answer 33

vascular permeability

Question 34

inhibition of angiogenesis, clearance of pulmonary edema, and protection of reperfusion injury are all actions of what?

Answer 34

lipoxins

Question 35

Current drugs for ___ include 5-LOX inhibitors, and LT-receptor antagonists

Answer 35

asthma

Question 36

Eicosanoids act via a __ trans-membrane __ ___ coupled receptor

Answer 36

7; G protein