Eicosanoids Flashcards
Three major classes of eicosanoids:
- Prostaglandins (PGs)
- Thromboxanes (TXs)
- Leukotrienes (LTs)
…… cleaves PIP2 to generate arachidonic acid and Lyso-PIP2
Phospholipase A2
Functions of Eicosanoids:
• Produce a wide range of biological effects of the inflammatory response
– Intensity and duration of pain and fever
– Reproductive function (including the induction of labor)
The following are characteristic of …….
– Inhibiting gastric acid secretion
– Regulating blood pressure through vasodilation or constriction
– Inhibiting, or, activating platelet aggregation and hence regulation of thrombosis
Eicosanoids
What inhibits the synthesis of arachidonic acid?
Corticosteriods
What inhibits Cycloxygenase 1 and 2 (COX 1)?
Aspirin and Other NSAIDS
Eicosanoids function by using specific receptor-mediated G-protein linked signaling pathways that result in the …………
Increase in either c-AMP levels or an increase in intracellular calcium
If present in a phospholipid, arachidonic acid will be at the …… position
C-2 position
Phospholipase A2 acts on phosphatidyl-inositol and releases …….
Arachidonic Acid
The immediate dietary precursor of arachidonate is ………..
Linoleic Acid
What is the result of inhibiting both COX 1 and Cox 2?
Reduced production of both prostaglandins and thromboxanes
Prostacyclin (PGI2) produced by …………… and Thromboxane A2 (TXA2), produced by ……………., play opposing key roles in regulating platelet aggregation and vasodilation
Endothelial Cells
Platelets
The following functions are characteristic of......... Platelet Aggregation Vasoconstriction Mobilizes intracellular calcium Contraction of smooth muscle
Thromboxane A2 (TXA2)
The following functions are characteristic of………
Vasodilation
Inhibits platelet Aggregation
Prostacyclin (PGI2)
How does aspirin inhibit COX1 and COX2?
Aspirin inhibits COX-1 and COX-2 irreversibly by acetylation of a serine amino acid side chain in the active site of these enzymes
The result is to decrease synthesis of eicosanoids
Aspirin’s inhibition of COX1 and COX2 results in……
-A decrease in platelets aggregation due to the reduced synthesis of TXA2 by platelets
Two different types of PUFA’s:
2- Series (linoleic acid)
3-Series (linolenic acid)
2-Series (linoleic acid) is derived from…… and produces ……
Arachidonic Acid
PGI2 and TXA2
3-Series (linolenic acid) is derived from…… and produces ……
Eicosapentaenoic Acid
PGI3 and TXA3
Either ……….. or ………….can be released by activation of PLA2 and used for eicosanoid synthesis.
EPA or arachidonic acid
TXA3 (from EPA) is ………… potent than TXA2 (from arachidonic acid) in platelet aggregation
Less
Arachidonic Acid is converted to 5-Hyroperoxyeicosatetrainoic acid (HPETE) by …………
5-HPETE is then converted into Leukotriene A4 (LTA4)
5-Lipoxygenase
LTC, LTD, LTE and LTF contain either a peptide or cysteine in their structure and are therefore called
Cysteinyl-leukotrienes
The ……………..are released during anaphylaxis and they are components of the slow-reacting substance of anaphylaxis (SRS-A). They are much more potent than histamine.
Cysteinyl-leukotrienes
The following are characteristic of ……
• Airflow obstruction
• Increased secretion of mucus
• Bronchoconstriction
• Infiltration of inflammatory cells in the airway wall
Asthma
Asthma treatment can include ……..of leukotriene synthesis or receptors.
Inhibition
How do drugs inhibit leukotriene action?
1) Inhibit the release of arachidonic acid (cortisol), this also leads to less PG and TX synthesis
2) Inhibit of 5-lipoxygenase activity (results in reduced leukotriene synthesis)
3) Act as Cysteinyl-leukotriene receptor antagonists
Prostaglandin E2 (PGE2) is mainly synthesized in the…..
Most Tissues, especially kidney
Functions of Prostaglandin E2:
Mediator of inflammation;
Vasodilation;
Relaxes smooth muscle;
Used to induce labor
