Section 26.5 Prostaglandins 013the aggregation of platelets. The levels of these two compounds must be carefully con-
trolled to maintain the proper balance in the blood.
Aspirin (acetylsalicylic acid) inhibits the cyclooxygenase activity of prostaglandin
endoperoxide synthase. It does this by transferring an acetyl group to a serine hydrox-
yl group of the enzyme (Section 17.10). Aspirin, therefore, inhibits the synthesis of
prostaglandins and, in that way, decreases the inflammation produced by these com-
pounds. Aspirin also inhibits the synthesis of thromboxanes and prostacyclins. Over-
all, this causes a slight decrease in the rate of blood clotting, which is why some
doctors recommend one aspirin tablet every other day to reduce the chance of a heart
attack or stroke caused by clotting in blood vessels.
Other anti-inflammatory drugs, such as ibuprofen (the active ingredient in
and ) and naproxen (the active ingredient in ), also inhibit
the synthesis of prostaglandins. They compete with either arachidonic acid or the
peroxy radical for the enzyme’s binding site.
Both aspirin and these other nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit
the synthesis of all prostaglandins—those produced under normal physiological condi-
tions and those produced in response to inflammation. The production of acid in the
stomach is regulated by a prostaglandin. When prostaglandin synthesis stops, therefore,
the acidity of the stomach can rise above normal levels. New drugs— and
—that recently have become available inhibit only the enzyme that produces
prostaglandin in response to stress. Thus, inflammatory conditions now can be treated
without some of the harmful side effects.
VioxxCH 3OOOO
SCelebrexCH 3F 3 CCH 3ON NO
SVioxx®
Celebrex®Motrin®, Nuprin® Aleve®
Advil®,CH 3 C O + HOCH 2 + HOHOOC
acetylsalicylic acid
aspirincyclooxygenase
active enzymeserine hydroxyl
groupacetyl
groupcyclooxygenase
inactive enzymeOCH 3 C OCH 2OHOOCCOOHOCCH 3O
aspirinCH 3 CHCH 2 CHCOOHCH 3 CH 3CHCOOHCH 3ibuprofen CH 3 O
naproxen