Eicosanoids Flashcards
Eicosanoids are important bio-active agents synthesized form what?
PUFAs - 20 carbons long
Prostanoids are synthesized by the ___ pathway
cyclooxygenase (COX)
The leukotrienes and lipoxins are synthesized by the ____ pathway
lipoxygenase
Both the COX pathway and the lipoxygenase pathway start with a 20 carbon PUFA, usually ____ acid
arachidonic
The arachidonic acid is derived from membrane ____. It is released by the action of ____ ___
phospholipid; phospholipase A2
What is the rate-limiting step in prostaglandin synthesis?
hydrolysis of arachidonic acid
Agents which stimulate the production of prostaglandins do so by stimulating the activity of what?
phospholipase A2
The other C20 PUFAs may serve as precursors. EPA (C20:5) is obtained from what? It is a w-__ acid
diet; 3
PGH2 is the first prostaglandin product and is the common intermediate of what?
- the other important prostaglandins
2. the thromboxanes
Prostaglandin synthase (PGS) has two components: cylclooxygenase (COX) and PG hydroperoxidase. What do these two components catalyze?
- COX: catalyzes synthesis of PGG2
2. PG hydroperoxidase catalyzes the formation of PGH2 from PGG2
PG hydroperoxidase requires what?
GSH
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 ___.
PGH1; PGH3
There are two forms of COX. COX1 is a ____ enzyme found where?
constitutive; found in gastric mucosa, platelets, vascular endothelium and kidney
There are two forms of COX. COX2 is a ___ enzyme found where?
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
COX2 induction is inhibited by ____
glucocorticoids
The ____ inhibit COX.
ex: aspirin, ibuprofen etc.
NSAIDS
Aspirin inhibits COX__ more than COX__
2; 1
Aspirin’s mechanism of action involves ___ of the COX enzyme
acetylation
Steroid anti-inflammatory drugs (hydrocortisone, prednisone) act by inhibiting this enzyme’s activity.
phospholipase A2
PGE2 and PGF2 are major prostaglandins produced where?
kidney and spleen
PGE2 is produced by what?
macrophages, mast cells, and B cells
PGD2 is produced by ___ cells
mast
PGI2 and PGF2 are major prostaglandins produced by ___ ___
blood vessels
note: PGI2 is an important inhibitor of platelet aggregation
Thromboxane A2 (TXA2) is a major prostaglandin produced by ____
platelets
note: stimulates platelet aggregation
The half-life of TXA2 is very long. True or false?
False; very short - it is rapidly converted to the inactive TXB2
In what 3 ways do prostaglandins mediate inflammation?
- induce redness and heat
- increase capillary permeability
- pyrogens activate synthesis of prostaglandins
Prostaglandins stimulate ____ contraction and inhibit ____ acid secretion
uterine; gastric
HPETEs are highly reactive intermediates that are rapidly converted to their analogous _____ acids or to ____
HETEs; leukotrienes
The most important products of lipoxygenases in humans is ____-____ since these are converted into the leukotrienes
5-HPETE
Leukotrienes are important secretory products of ____ and each one contains a conjugated ___ group
leukocytes; trienoic
note: the subscript number refers to the total number of double bonds
Leukotrienes mediate ____ disorders
inflammatory
SRS-A is a mixture of LTC4, LTD4, and LTE4 and is a potent stimulator of the ___ ___ musculature
bronchial airway
LTB4, LTC4, LTD4, and LTE4 increase ___ ___
vascular permeability
inhibition of angiogenesis, clearance of pulmonary edema, and protection of reperfusion injury are all actions of what?
lipoxins
Current drugs for ___ include 5-LOX inhibitors, and LT-receptor antagonists
asthma
Eicosanoids act via a __ trans-membrane __ ___ coupled receptor
7; G protein
