August 2, 1995 in Nation/World

Scientist Uncovers Aspirin Mystery Biochemist’s Solution May Lead To A More Effective Pain Reliever

Newsday
 

At long last, the mystery of how aspirin relieves pain may have been solved. And the solution, scientists report, could reveal how to make a drug that can rid you of a headache, among other things, without causing an upset stomach.

Though the first aspirin pills were not marketed until 1899, acetylsalicylic acid has been used as a pain reliever in one form or another for at least 2,300 years. Today, Americans consume 30 billion pills a year.

But scientists haven’t had a clue as to how the drug works. Until now.

In Tuesday’s edition of the journal Nature/Structural Biology, biochemist Michael Garavito of the University of Chicago Medical Center is to present evidence that he may have solved the mystery.

For years, Garavito has been using high-tech X-ray technology to get 3-D pictures of the human enzyme called prostaglandin H2 synthetase, or PGHS. As he developed a sense of the enzyme’s tertiary structure, Garavito realized that aspirin fit neatly inside a sort of tunnel that runs through the enzyme.

Once this happens, Garavito said, “it physically closes and locks the door on the (enzyme) factory.”

Garavito said Monday that he found two different types of PGHS, both of which are knocked out of commission by aspirin. The first, PGHS-I is responsible for several cleanup operations in the body, including eliminating irritating stomach acids. When aspirin knocks out PGHS-I, a stomachache is usually the result unless buffering foods or neutralizing chemicals are present.

But the key to pain relief is PGHS-II. That enzyme turns certain dietary fats into a class of powerful hormones called prostaglandins. High levels of prostaglandins lead to fevers, tissue and muscle inflammation, water retention and buildups in fats that can lead to heart disease. Aspirin locks the door on that factory as well, Garavito said, and pain decreases as inflammation goes down.


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