Cyclooxygenase presentation

Cyclooxygenases (COXs) are enzymes that catalyze the rate-limiting step in the conversion of arachidonic acid to prostaglandins. Cyclooxygenases are also known as Prostaglandins H Synthase.

1. CycloOXygenase 2 (COX 2) BY Mehwish Nawaz

2. Cyclooxygenases (COX) Cyclooxygenases (COXs) are enzymes that catalyze the rate-limiting step in the conversion of arachidonic acid to prostaglandins Cyclooxygenases are also known as Prostaglandins H Synthase. This enzyme converts arachidonic acid, a fatty acid in cell membranes, into prostaglandins, modified fatty acids attached to a ring of five carbons. Prostaglandins (PGs) are hormone-like bioactive substances involved in many physiological and pathological processes

3. Biosynthesis of Prostanoids

4. Types of COX enzyme Conversation of Arachidonic acid to Prostaglandins is mediated by Cyclo- oxygenases which are of two types COX 1 and COX 2. COX 1 : Constitutive , activated by physiologic stimuli. COX 2 : Inducible by Pro-inflammatory stimuli It has two active site COX-1 and COX-2 are very similar in structure (60- 65% of the sequence is conserved), however they are expressed in different parts of the body.

5. Cyclooxygenase site , where arachidonic acid is converted into the hydroperoxy endoperoxide ProstaGlandin G2 (PGG2). Heme with peroxidase activity , responsible for the conversion of PGG2 to PGH2. Which is then converted into prostanoids (PGD2, PGF2 α PGE2, thromboxane A2, PGI2)by specific isomerase enzymes Active site of COX

6. Actions of Cyclooxygenases

7. COX 2 COX 2 is an Inducible enzyme that acts to speed up the production of certain chemical messengers, called prostaglandins that play a key role in promoting inflammation. COX-2 is located in macrophages, leukocytes and fibroblasts. Structural Domains of COX 2 N-terminal epidermal growth factor (EGF) A Membrane Binding Domain (MBD) A large C-terminal globular catalytic domain

8. Structure of COX 2

9. Prostaglandins produced by COX 2 The prostaglandins produced by COX 2 are Used for signaling pain and inflammation. It Produces prostaglandins for inflammatory response. Production is stimulated by inflammatory cytokines and growth factors.

10. MECHANISM OF ACTION OF PROSTAGLANDINS VIA cAMP PATHWAY Prostaglandin I2 (PGI2, prostacyclin). It causes relaxation of vascular smooth muscle and inhibits platelet aggregation.

11. MECHANISM OF ACTION OF PROSTAGLANDINS VIA IP3/DAG PATHWAY

12. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) NSAIDs produce anti-inflammatory, anti-pyretic and analgesic effects. Finding ways of reducing pain and inflammation are key roles of NSAIDs The mechanism of these drugs is due to their binding ability to the active sites of COX , preventing the catalysis of Arachidonic acid to prostaglandins

13. NSAIDs NSAIDs binds irreversibly to COX enzymes and inhibit their action i.e the conversion of Arachidonic acid to the prostaglandins. NSAIDs acetylates the actives site of COX enzyme which causes inhibition. Some examples of NSAIDs are: Aspirin ibuprofen Piroxicam etc

14. Side effects of NSAIDs

15. Selective drug targeting of COX 2

16. Categories of NSAIDs

17. COX 2 Inhibitors (COXIBs) As COX 2 has role in inflammation and pyrexia. So it is desirous to inhibit COX-2. There are different types of drugs that are used to inhibit COX-2 enzyme including Celecoxib. COX-2 inhibitors (COXIBs) are a special category of NSAIDs that target only COX-2 enzymes. COX-2 inhibitors also don’t offer the same kind of protection against heart disease.

18. Chemical structures of COXIBs

19. Celecoxib Since aspirin is nonselective to both COX1 and COX2 it shows duel effects Celecoxib shows selectivity to COX2 thus inhibiting only the inflammatory prostaglandins and not the COX1 house keeping prostaglandins

20. Why is Celecoxib selective to COX 2?

21. The mechanisms by which COX-2 contributes to cancer Prostaglandins and immune response

22. Different mechanisms through which the COX-2-derived prostaglandins are involved in the carcinogenesis

23. Regulation of COX 2 in Cancer

24. Acknowledgement https:// www.google.com/search?q=cox+1+and+cox2&source=lnms&tbm=isch&sa=X&ved=0ahUKEwi7nNvQy9HfAhUDThUIHVBwDBwQ_AUIDigB&biw=1455&bih=645#imgrc=wQ1bhLPPRHdsMM https://www.google.com/search?q=HUSSAIN+BIOLOGY&oq=HUSSAIN+BIOLOGY&aqs=chrome.. 69i57j0.5468j0j9&sourceid= chrome&ie =UTF-8 https :// www.google.com/search?q=cox+1+and+cox2&source=lnms&tbm=isch&sa=X&ved=0ahUKEwi7nNvQy9HfAhUDThUIHVBwDBwQ_AUIDigB&biw=1455&bih=645#imgrc=91aPEspniQ06LM