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.
1.COX 1 : Constitutive , activated by physiologic stimuli.
2.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.

6. 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, PGF2α PGE2,
thromboxane A2, PGI2)by specific isomerase enzymes
Active site of COX

7. Actions of Cyclooxygenases

8. 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

9. Structure of COX 2

10. 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.

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

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

13. 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

14. 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

15. Side effects of NSAIDs
Aspirin and other similar NSAIDs lead to excessive production of
stomach acid as well as ulceration and gastrointestinal bleeding.
NSAIDs can prolong the bleeding time
NSAIDs can increase blood pressure.
These all side effects are due to the inhibition of COX1’s house
keeping role.

16. Selective drug targeting of COX 2

17. Categories of NSAIDs
NSAIDS can be divided into the following
categories:
Non-selective COX inhibitor (Naproxen,
ibuprofen and piroxicam).
Selective COX-2 inhibitors (meloxicam,
Celecoxib and diclofenac).

18. 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.

19. Chemical structures of COXIBs

20. 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

21. Why is Celecoxib selective to COX 2?

22. The mechanisms by which COX-2 contributes
to cancer Activation of
carcinogens
Prostaglandins
and Apoptosis
Prostaglandins
and increased
invasiveness
Prostaglandins
and
Angiogenesis
Prostaglandins
and cell
proliferation
Prostaglandins
and immune
response

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

24. Regulation of COX 2 in Cancer

25. Acknowledgement
• https://www.google.com/search?q=cox+1+and+cox2&source=lnms&t
bm=isch&sa=X&ved=0ahUKEwi7nNvQy9HfAhUDThUIHVBwDBwQ_AU
IDigB&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&t
bm=isch&sa=X&ved=0ahUKEwi7nNvQy9HfAhUDThUIHVBwDBwQ_AU
IDigB&biw=1455&bih=645#imgrc=91aPEspniQ06LM