Ecosanoids: Nishimoto Flashcards
Name the 3 Eicosanoid derivatives.
Prostaglandins
Leukotrienes
Thromboxanes
Type of eicosanoid secreted by a cell depends on the cell type and its enzymes. With that in mind, what eicosanoid derivatives do endothelial cells secrete?
Prostaglandins- inhibit coagulation
WHat type of eicosanoid to platelets make/secrete?
Thromboxanes - stimulate aggregation and clotting
What fatty acid is the precursor to eicosanoids?
Arachidonic Acid
Can arachidonic acid be synthesized in the body? If so, how?
Yes, from 18-C FA’s like Oleic acid and alpha-linoleic acid. Add 2 C with ELONGASE enzyme and BOOM! Arachidonic Acid.
Arachadonic acid is polyunsaturated. How many double bonds does it have?
4
Before incorporating itself into membrane phospholipids, what happens to Arachidonic acid?
It is activated by AcetylCoA
What is the major regulatory step of Eicosanoid synthesis?
The release of Arachidonic acid from the membrane by PHOSPHOLIPASE A2.
What inhibits Phospholipase A2?
Glucocorticoids - specifically Lipocortin. Glucocorticoids bind receptor and cause transcription of Lipocortin.
If Arachidonic Acid is acted on by lipoxygenase, what is the product? (general)
Leukotrienes
HETE
Lipoxins
If Arachidonic Acid is acted on by Cyclooxygenase and Peroxidase, what is the intermediate formed?
Prostaglandin H2 (PGH2)
PGH2 is a common precursor of what products?
Prostacyclin and other prostaglandins, and Thromboxanes.
Release of ArA from membranes is triggered by….
Hormonal stimuli: Epinephrine, Thrombin, Antigotensin II
What are the essential fatty acids we must ingest for the synthesis of eicosanoids?
Omega 3 and 6
If Arachidonic acid is acted on by CYP450 what is the product?
Epoxides
By what mechanism do PGD, PGI,and PGE work?
The Adenylyl Cyclase pathway. cAMP and PKA.
What eicosanoid derivatives work by increasing cytosolic calcium?
PGF2, TXA2, and Leukotrienes
How long is the lifespan of an eicosanoid?
Seconds to minutes. SHORT.
Which Prostaglandin is more reduced? PGA or PGF?
PGF is most reduced. PGA is most oxidized.
What does the number at the end of a prostaglandin abbreviation indicate?
The number of double bonds contained within that prostaglandin and its precursor.
PGI PGE and PGD cause what to happen?
Vasodilation and adenylyl cyclase pathway
Inhibit: Platelet aggregation, leukocyte agregation, and lymphocyte migration.
What eicosanoid is secreted by platelets? What does it do?
Thromboxane A2. (TXA2) - stimulates aggregation, causes vasoconstriction.
What does PGF2-alpha do?
VasoCONSTRICTION, bronchoCONSTRICTION, and smooth muscle contraction
What prostaglandins do vascular endothelial cells secret?
PGI
PGE
PGD
NSAIDS inhibit what, in the synthesis of PGH2?
Cyclooxygenase
What cells synthesize leukotrienes?
Leukocytes
What enzyme catalyzes the reaction of arachidonic acid into leukotrienes?
Lipoxygenase
What is a common intermediate of both HETEs and Leukotrienes?
HPETE
What is a lipoxin?
A derivative of Arachidonic acid with 3 -OH groups
How do lipoxygenases work on ArA?
They introduce an unstable proxy oxygen into the structure to make HPETE, which quickly rearranges into either Leukotrienes or HETEs.
What is the role of Leukotrienes in the inflammatory response?
increase vascular permeability, recruits WBCs to the area, IL-1, IL-2.
