B IO C H E M IS T R Y PE A R L S
Conversion of arachidonate to PGH2 via cyclooxygenase catalysis is
a key regulatory step in prostanoid biosynthesis.
Aspirin has emerged as a very useful antithrombotic agent because
of its action against platelet cyclooxygenase activity.
The coxibs (such as celecoxib) derive their exquisitely selective
inhibition of COX-2 cyclooxygenase from their ability to form
noncovalent EI' complexes with COX-2 and not with COX-1.
The selectivity of coxibs for COX-2 over COX-1 gives them antiin-
flammatory and antiproliferative actions with reduced GI side
effects, but it also makes them ineffective as antiplatelet agents
and thus increases risks from myocardial infarction and stroke.
Blobaum AL, Marnett LJ. Structural and functional basis of cyclooxygenase inhi-
bition. J Med Chem 2007;50:1425-41.
Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science
Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular conse-
quences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin
Parfitt JR, Driman DK. Pathological effects of drugs on the gastrointestinal tract:
a review. Hum Pathol 2007;38:527-36.