Eicosanoids Flashcards
What is the purpose of the eicosanoids?
They are a 20 carbon structure that control/modulate several body functions by acting on extracellular surface receptors.
Essential fatty acids are ________ fatty acids and are the precursor for what?
polyunsaturated (PUFA); EFAs are the precursors of hormone-like molecules - the eicosanoids.
What are the parents of the omega 3 and omega 6 fatty acid families?
a-Linolenic (w3) and linoleic (w6)
What are the 4 types of eicosanoids?
Prostaglandins (PG), Leukotrienes (LT), Prostacyclins, and Thromboxanes (TX)
Which two eicosanoids have opposing actions?
Prostacyclins and Thromboxanes
What are the opposing actions of prostacyclins and thromboxanes?
Prostacyclins (endothelium): anti-aggregation of cells, vaso-dilation, lowers BP
Thromboxanes (platelets): aggregation of cells, vaso-constriction, raises BP
How do eicosanoids act as local signaling molecules?
They connect to G-proteins and act locally to produce local effects.
Which cells do the leukotrienes act upon?
WBCs - specifically the phagocytes: macrophages, neutrophils, and monocytes)
What is the parent molecule of prostaglandins?
Prostanoic acid
Bonds projecting from the ring at position 8 and 12 of prostanoic acid is in which configuration?
Trans
All natural prostaglandins have a hydroxyl at which carbon?
C-15
What does the additional letter on PG designate? (i.e. PGA)
Variation in ring structure and substiuents
What is the designation of the numerical subscript of PG?
Number of double bonds in the hydrocarbon chain
In PG what are the configurations for the following double bond locations? (13,14), (5,6), and (17, 18)
(13,14): Trans
(5,6): Cis
(17,18): Trans
True/False: Acetyl CoA can be converted to glucose…
FALSE!!! Acetyl CoA CANNOT be converted to glucose!
How are TX similar to PG?
TX ring structure is a 6 carbon oxy-heterocycle
What are LT derived from and what is their structure?
They are derived from HPETEs and they are an open-chain structure containing 3-5 double bonds.
What is the additional letter for the LT?
It is the specific modification of the parent chain
Where is arachidonic acid (AA) found?
It is inserted into the C-2 position of membrane phospholipids and influences membrane properties.
How is AA released from membrane phospholipids?
The major releasor of AA is phospholipase A2, which is also used to remodel the membrane. The amount of AA released is in direct proportion to how much is available.
Which part of the cell membrane phospholipids is inhibited by steroids?
Steroids inhibit the phospholipases
What are inhibitors of cyclooxygenase? (COX1 or COX2 inhibitors)
Pharm.: Aspirin, indomethacin
Natural: Ginger & Omega 3
What is the natural inhibitor of 5- (LOX)?
Ginger
What are natural inhibitors of Prostacyclin (PGI2)?
Selenium, curcumin, and zinc
What is a natural inhibitor of the production of both prostacyclins and TXs?
Zinc
What is a natural inhibitor of TXs?
Garlic and curcumin
What are the direct parent materials of prostacyclins and TXs?
Prostaglandin H2 (which derived from PGG2, from COX)
Which material creates HPETE?
5-Lipoxygenase (LOX)
HPETE creates 12-Lipoxygenase which in turn creates which two materials and what do those materials do?
Lipoxin A (LXA4) and Lipoxin B (LXB4): Inhibit neutrophil adhesion and chemotaxis
HPETE creates Leukotriene A4, C4, D4, and E4. Which are the most powerful vasoconstrictors known and what do they do?
Leukotriene C4, D4, and E4. They are responsible for slow reacting vasoconstriction, brochospasm, and increased vascular permeability. (anaphylaxis)
5-HPETE creates 5-HETE which is responsible for the creation of which reaction and which leukotriene?
Chemotaxis; leukotriene B4
Aside from prostacyclins and TX, what does PGG (followed by PGH2) create and what are their functions?
PGD2 and PGE2; vasodilation and increased vascular permeability
Cyclooxygenases (COX) initiates conversion of arachidonate and other precursors into ______ and ______.
PGs and TXs
COX 1 and COX 2 are considered the ________ of all cells.
Housekeeper
Lipoxygenases (LOX) converts arachidonate into _________ which is the precursor for which eicosanoids?
HPETEs; leukotrienes or into lipoxins
What are the system types of COX versus LOX?
COX - cyclic pathway
LOX - linear pathway
Eiscosanoids have a short half-life. How are they inactivated?
It is inactivated when the hydroxyl at C15 is oxidized to a ketone
What is the anti-inflammatory action of steroids on arachidonic acid?
It is mediated by inducing synthesis of a protein (lipocortin) which INHIBITS Phospholipase A2.
NSAIDS are __________ of COX. What are 2 NSAIDS and which one is reversible and which one is irreversible?
inhibitory; Aspirin (irreversible) and Ibuprofen (reversible)
What is special about acetaminophen?
It is not an NSAID, so therefore it is not anti-inflammatory; it is a pain reliever.
COX1 is a constitutive enzyme of what?
gastric mucosa, platelets, vascular endothelium and kidney; (they produce “housekeeping” prostaglandins)
How is COX2 derived and what does it produce?
It is inducible; produced in response to inflammation (produces inflammatory prostaglandins)
What are 3 stimulus for the production of arachidonic acid?
- ) Thrombin (platelet aggregation)
- ) Histimine
- ) Cytokines: IL-1, IL-6, and TNFg
What does the number after LOX (i.e. LOX 5, LOX 12, LOX 15) designate?
It designates where oxygen is introduced.
Where do we get our main sources of arachidonic acid? Why?
Diet; it is inefficiently synthesized from linoleic acid because delta 5 and delta 6 desaturases are slow enzymes
The capacity for arachidonic acid synthesis is _________ with gamma-linolenic acid (GLA) in the diet.
greater
Which parental eicosanoids compete for placement in membrane phospholipids?
Linoleic and a-linolenic compete with arachidonic acid
What product formed from GLA is also inserted into the C2 position of membrane phospholipids?
Most of the DGLA
Ultimately, which 7 products compete for placement into the membrane?
Oleic, linolenic, a-linoleic, GLA, DGLA, w6, and w3
What are the 3 major types of omega-3 fatty acids in the diet?
a-linolenic (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)
What is ALA converted to? What is the capacity for this pathway?
EPA and DHA; this pathway has a limited capacity (1-5% is actually converted)
True/False: Omega 3 and Omega 6 fatty acids compete for placement in membrane phospholipids.
True
What percent of arachidonic acid is synthesized in the body?
Only 5%, it is a highly inefficient system
True/False: GLA’s are omega 3 fatty acids.
FALSE! They are NOT omega 3
What are the products of DGLA?
Series 1 prostaglandins (PGE1) and thromboxanes (TXA1, LT3)
Arachidonic acid is the precursor for which series eicosanoids? What processes are promoted by these?
Series 2 (TX2 & LT4); promotes inflammatory responses and resolution of inflammation
What is the precursor of the series-3 eicosanoids? What are the consequences?
EPAs; they are less inflammatory
What are specialized lipid pro-resolving mediators and what are they important for?
Lipoxins; important control elements of inflammation (repair process - recruits cells & chemical mediators)
What is the function of lipoxins?
They mediate reduction in inflammation.
Lipoxins are a product of what? Which makes them which type of omega fatty acid?
arachidonic acid; omega 6
Synthesis of lipoxin epimers which physiological activity can be induced by what?
Aspirin
EPA and DHA serve as precursors for what potent anti-inflammatory lipids and what are they made from?
Resolvins (RVs - resolves inflammation) and Protectins (PDs)
D series resolvins are made from DHA
E series resolvins are made from EPA
Low dose aspirin induces synthesis of what?
Resolvins
What tissue does protectin operate and what does it protect?
They operate within brain tissue and protect retinal epithelial cells
How can specialized lipid pro-resolving mediators arise from transcellular synthesis?
Cell to cell interactions involving the transfer of biosynthetic intermediates.
