What is the Difference Between COX-1 and COX-2

The main difference between COX-1 and COX-2 is that COX-1 forms prostaglandins involved in regulating homeostatic functions in the body, whereas COX-2 forms prostaglandins that mediate pain and inflammation.

COX-1 and COX-2 are two isozymes of cyclooxygenases that produce prostaglandins which are natural chemicals in the body vital to create inflammation.  

Key Areas Covered

1. What is COX-1
– Definition, Facts, Importance
2. What is COX-2
– Definition, Facts, Importance
3. Similarities Between COX-1 and COX-2
– Outline of Common Features
4. Difference Between COX-1 and COX-2
– Comparison of Key Differences

Key Terms 

COX-1, COX-2, Cyclooxygenase-1, Cyclooxygenase-2, Prostaglandin G/H Synthase 1, Prostaglandin H2 Synthase 1, Prostaglandin-Endoperoxide Synthase 1

What is COX-1

COX-1 or cyclooxygenase-1 is one of the two cyclooxygenases that are the enzymes in the biosynthetic pathway of prostaglandins from arachidonic acid. Prostaglandin G/H synthase 1, prostaglandin H2 synthase 1, and prostaglandin-endoperoxide synthase 1 are the other names of COX-1. PTGS1 gene is the gene that encodes for COX-1. Also, COX-1 occurs in the platelets, renal tubule cells, and GI mucosal cells. Importantly, it has a housekeeping role in tissue homeostasis. It forms PGE₂ and PGI₂, exerting cytoprotective effects on gastric function. They increase the bicarbonate and mucus secretions, reduce pepsin and gastric acid secretions, and maintain adequate blood flow to the mucosa. Also, they promote the secretion of protective mucus in the duodenum. Their inhibition causes ulceration and bleeding in the stomach and duodenum.

Figure 1: COX-1

Furthermore, COX-1 synthesizes TxA₂ in platelets, stimulating vasoconstriction and platelet aggregation. The inhibition of COX-1 leads to the inhibition of platelet aggregation. In arterial thrombosis, the inhibition of COX-1 inhibits platelet aggregation. In the endothelium, the production of PGI₂ inhibits platelet aggregation and exerts vasodilation.

What is COX-2

COX-2, or cyclooxygenase-2, is the second type of cyclooxygenase. Prostaglandin-endoperoxide synthase 2 is another name for COX-2. PTGS2 is the gene that encodes COX-2. COX-2 produces PGH2 from arachidonic acid. It is a two-step reaction, and COX-1 catalyzes the first reaction of converting arachidonic acid into PGG₂. COX-2 catalyzes the reduction of PGG₂ into PGH₂. PGH₂ regulates the dilation and constriction of blood vessels. Also, it stimulates platelet aggregation.

Figure 2: COX-2

Moreover, both COX-1 and COX-2 regulate kidney function. Sodium retention and peripheral edema result from the inhibition of COX in the kidney. Notably, COX-2 is predominantly an inducible enzyme responsible for the production of prostanoids in inflammation. 

Similarities Between COX-1 and COX-2

• COX-1 and COX-2 are two isoenzymes.
• They are cyclooxygenases that create prostaglandins important in inflammation.
• They crease other prostanoids, such as thromboxane as well.
• Inhibition of COX relieves symptoms of inflammation and pain.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen inhibit cyclooxygenase. 

Difference Between COX-1 and COX-2

Definition

COX-1 refers to a predominantly constitutive enzyme widely expressed in most tissues, including gastrointestinal (GI) mucosa, platelets, endothelium, kidneys, and uterus. In contrast, COX-2 refers to an enzyme that speeds up the production of certain chemical messengers called prostaglandins that play a key role in promoting inflammation.

Expression

COX-1 is a constitutively expressed enzyme, while COX-2 is an inducible form. 

Occurrence

COX-1 occurs in GI mucosal cells, renal tubule cells, and platelets, while COX-2 occurs in fibroblasts, chondrocytes, endothelial cells, macrophages, and mesangial cells. 

Function

COX-1 forms prostaglandins involved in regulating homeostatic functions in the body, while COX-2 forms prostaglandins that mediate pain and inflammation.

Types of Prostaglandins

COX-1 forms PGE_2, PGG_2,and PGI₂ while COX-2 forms PGH_2.

Conclusion

In brief, COX-1 and COX-2 are two isoenzymes of cyclooxygenase that produce prostanoids from arachidonic acid. COX-1 is expressed constitutively in GI mucosal cells, renal tubule cells, and platelets. The primary function of prostaglandins produced by COX-1 is to regulate homeostatic function. In comparison, COX-2 is fibroblasts, endothelial cells, macrophages, chondrocytes, and mesangial cells. Importantly, it is an inducible form of cyclooxygenase, mediating pain and inflammation. Therefore, the main difference between COX-1 and COX-2 is their function. 

References:

1. Cyclooxygenase 1. Cyclooxygenase 1 – an overview | ScienceDirect Topics. (n.d.). 

Image Courtesy:

1. “PROSTAGLANDIN H2 SYNTHASE-1 COMPLEX” By Cytochrome c at English Wikipedia – Own work (CC-BY SA 3.0) via Commons Wikimedia
2. “Cyclooxygenase-2” By Cytochrome c at English Wikipedia – Own Work (CC-BY SA 3.0) via Commons Wikimedia