|MadSci Network: Biochemistry|
The active ingredient in aspirin is acetylsalicyacetic acid (ASA). It works by chemically modifying an enzyme which is responsible, in part, for causing fever and inflammation. The enzyme is known by several names in the scientific literature, including: cyclooxygenase (COX), prostaglandin synthase (PGS). It turns out that there are two closely related forms of this enzyme, so they are now numbered: COX-1 and COX-2 or PGS-1 and PGS-2. The acetyl group in ASA reacts with a permanently binds to the active site of these enzymes, such that they no longer work. However, over a period of several hours, most cells make new enzyme which does work. That is why you have to keep taking aspirin for the effect to last. So I have not really explained how these two related enzymes cause fever and inflammation. Well it turns out that the second form of the enzyme (i.e., COX-2 or PGS-2), is turned on during an infection or injury. This enzyme is responsible for the generation of compounds known as prostaglandins (thus the name prostaglandin synthase). It is the production of prostaglandins (PG) in the brain that induce fever. PG made elsewhere in the body, let's say during an infection, promote local inflammation and swelling. This is meant to promote the activation of immune cells which are needed to fight the infection. However, too much inflammation can be bad (i.e., it cause pain!). Finally, I thought you might like to know why too much aspirin is bad for you, at least bad for your stomach. As the aspirin dissolves in your stomach it blocks the COX-1 enzyme in the cells lining the stomach. This COX-1 is needed to promote the secretion of mucous that is responsible for protecting your stomach lining from the acid in your stomach. Too much aspirin or frequent use can cause irritation of the stomach lining and eventually may lead to a bleeding ulcer. Ouch! The drug companies have been developing new drugs that work on COX-2, but leaves COX-1 alone. In theory these drugs should help reduce pain and inflammation without the bad side effects of aspirin. A few of these new anti-inflammatory drugs are out in the marketplace now, but they start out as prescription drugs initially, so you may not have read much about them.
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