COX Flashcards
Derivation of Arachidonic Acid
Prostaglandins
Process by which Arachidonic acid becomes prostaglandins (general)
Cleaved from plasma membrane by PLA2 (Ca2+ dependent)
Oxygenated, cyclized, and reduced by COX
Exact mechanism of COX
Oxygenase activity of oxygenating Arachidonic Acid and cyclizing it to form PGG2. Then peroxidase activity reducing PGG2 into PGH2.
Difference between COX1 and COX2
1: constitutive, expressed in all cells, immediate reaction
2: inducible, not expressed in platelets, delayed reaction, associated with inflammation
How does aspirin work?
Irreversibly inhibiting COX1/2 by covalently binding
Acetylates a serine
What do bradykinins release?
RCS and PGS (probably don’t need to know)
Aspirin also blocks contractions due to bradykinin
Process of thromboxane (TXA2) production in platelets
Thrombin activates platelets, release contents and allow production of TXA2
Effects of thromboxin
Vasocontriction and platelet aggregation
Why does aspirin have protective CV effects?
Irreversibly inhibits both COX1/2, but only COX1 is expressed in platelets. Because platelets don’t have a nucleus, they cannot be upregulated like they can in endothelial cells. This causes a decrease in TXA2 released by platelets, but allows restoration of the PGI2 released by endothelial cells.
The PGI2 has vasodilating and inhibiting platelet aggregation effects, which prevents atherosclerosis` and protects the cardiovascular system.
Why don’ t COX2 inhibitors provide the desired funciton?
The goal was to selectively inhibit COX2 because COX1 inhibition causes a decrease in the mucus protecting PGEs in the stomach. However, only inhibiting COX2 means platelets are free to produce TXA2 an are not balanced by the production of PGI2. This leads to platelet aggregation and atherosclerosis.
