What Is Cyclooxegenase, and How Is It Involved in Inflammation?
Key takeaways:
Cyclooxygenase (COX) is an enzyme (protein) that helps create two important chemicals in the body: prostaglandin and thromboxane.
There are two main types of COX: COX-1 and COX-2. COX-1 is involved in many protective processes in the body, and COX-2 is mostly involved in inflammation.
Non-steroidal anti-inflammatory drugs (NSAIDs) block COX. There are different side effects depending on whether the NSAID blocks COX-1 or COX-2 more strongly.
Most people experience physical pain at some point in their life. Regardless of the type of pain you’ve experienced, it’s likely the sensation you felt was the result of inflammation. Inflammation (swelling) is the body’s response to an irritant, injury, or illness.
We typically hear about inflammation in a negative way, but it’s part of our immune system’s process to protect the body. Cyclooxygenase (COX) is a protein (enzyme) in our body that’s vital to the process of inflammation.
Below, we’ll cover everything you need to know about COX: what it is, how it works, and what medications block it from working.
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How does cyclooxygenase work in the body?
Cyclooxygenase (COX) is an enzyme that helps create prostaglandins. Prostaglandins are natural chemicals in the body that are vital to creating inflammation. High levels of prostaglandins are present in areas of the body that become inflamed. They contribute to the initial phase of inflammation — called acute inflammation — where symptoms like redness, swelling, and pain can be seen and felt.
Prostaglandins are made from a chemical called arachidonic acid (AA). AA is a type of fatty acid in the body. Fatty acids are the building blocks of fats, and are necessary for our body to function. COX is the enzyme that converts AA to prostaglandins.
COX is also responsible for converting arachidonic acid to thromboxane A2 (TxA2). TxA2 signals to our platelets when it’s time to form a clot. It’s also a vasoconstrictor, meaning it narrows our blood vessels.
This first step in creating TxA2 is converting arachidonic acid to prostaglandins. Then another enzyme — thromboxane A2 synthase — changes prostaglandin to thromboxane. But not all COX enzymes can carry out this process. It only happens with a type called COX-1.
What’s the difference between COX-1 and COX-2?
There are two main types of COX enzymes: COX-1 and COX-2.
COX-1
COX-1 is generally considered a “constitutive” enzyme. This means that it’s produced in the body regularly, regardless of whether we’re healthy, sick, or injured. Our bodies make it no matter what.
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COX-1 is involved in many processes, including:
Joining platelets together in the blood to stop bleeding (platelet aggregation)
Helping facilitate blood flow in the kidneys
Protecting your stomach lining
As mentioned above, COX-1 is also responsible for helping to create TxA2. Too much TxA2 can be a problem — it plays a role in causing heart attacks, stroke, and high blood pressure (hypertension).
COX-2
COX-2 is considered an “inducible” enzyme. This means it’s produced in higher amounts only under certain conditions. COX-2 is produced in situations where inflammation is actively occurring in the body.
Where are COX-1 and COX-2 found in the body?
COX-1 is found widely throughout the body. Locations where COX-1 is found include the:
Stomach lining
Kidneys
Uterus
Platelets (cells that form blood clots)
Blood vessels
Heart
COX-2 generally shows up in areas of the body where inflammation is occurring.
What medications block cyclooxygenase?
If you’ve ever taken a medication like ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn), you’ve taken a medication that blocks COX enzymes. These medications — called nonsteroidal anti-inflammatory drugs (NSAIDs) — are commonly used for everyday aches and pains, or to lower a fever. Other common examples of NSAIDs include aspirin, diclofenac (Voltaren) and celecoxib (Celebrex).
Several NSAIDs are available over-the-counter (OTC). Some are available by prescription, too. Most people use these medications to help relieve occasional muscle pain or fevers. But, they’re also used to treat pain from chronic conditions, like osteoarthritis and rheumatoid arthritis.
The most common NSAIDs — like ibuprofen, naproxen, and diclofenac — are called non-selective NSAIDs. They lower inflammation in the body and relieve pain. These NSAIDs work by blocking COX-2 from working. But since these NSAIDs are “non-selective,” they also block COX-1 just as much as COX-2.
Selective NSAIDs, like celecoxib, are called COX-2 inhibitors. They block COX-2 more strongly than they block COX-1.
Aspirin blocks both COX-1 and COX-2, but blocks COX-1 more. Remember that COX-1 helps platelets stick together, which can cause blood clots and lead to a heart attack or stroke. People who have had a heart attack or stroke before may take aspirin to prevent another one from happening.
What are the side effects of blocking COX?
Blocking COX-1 or COX-2 causes different side effects. It’s important to know what to look out for if you’re taking an NSAID. Different NSAIDs have different side effects because not all NSAIDs block COX-1 and COX-2 to the same degree.
But, there’s a potential effect on the kidney with all NSAIDs. In people with existing kidney problems, prostaglandins are important. They help raise blood flow in the kidneys. Since non-selective NSAIDs and COX-2 inhibitors stop prostaglandins from forming, they can cause your kidneys to not work as well. A kidney that doesn’t function normally can also cause high blood pressure.
Side effects of blocking COX-1
When COX-1 is blocked, you might feel gastrointestinal side effects. This is because COX-1 protects your stomach lining. Side effects include stomach upset and stomach bleeds. It could also include ulcers in the stomach, small intestine, or esophagus. Non-selective NSAIDs and aspirin may have these side effects. Selective COX-2 inhibitors, like celecoxib, have minimal gastrointestinal side effects.
Side effects of blocking COX-2
When COX-2 is blocked, heart problems can occur. This is because the normal balance of prostaglandins and TxA2 is affected. This is most common with COX-2 inhibitors, but can also occur with non-selective NSAIDs. When COX-2 is more strongly blocked, the body has less prostaglandins, but TxA2 levels are not lowered as much. Because high TxA2 levels can cause blood clots, heart attack and stroke are more likely.
The bottom line
Cyclooxygenase (COX) is an enzyme that helps create the chemicals prostaglandin and thromboxane (TxA2). Prostaglandins help create inflammation, and TxA2 helps your blood clot.
There are two types of COX: COX-1 and COX-2. COX-1 is involved in many maintenance processes in the body, and COX-2 is largely involved in inflammation. NSAIDs are medications that block COX-1 and COX-2. Depending on whether an NSAID blocks COX-1 or COX-2 more, they may have different side effects. Blocking COX-1 can cause gastrointestinal side effects, while blocking COX-2 can lead to heart problems.
Because NSAIDs carry different risks depending on how they affect COX-1 and COX-2, it’s important to discuss using them with your healthcare provider first.
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References
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