[Molecular structure and regulation of cyclooxygenase]

Prostaglandin (PG) endoperoxide synthase is a bifunctional enzyme with fatty acid cyclooxygenase activity (arachidonic acid----PGG2) and PG hydroperoxidase activity (PGG2----PGH2). The primary structure of the enzyme was determined recently by cloning and sequencing the cDNAs for sheep and mouse enzymes and the genomic DNA for the human enzyme. Aspirin selectively inhibits the fatty acid cyclooxygenase activity but not the PG hydroperoxidase activity by acetylating the serine #506. Several lines of evidence suggest that cyclooxygenase enzyme is inducible by several biofactors, such as EGF, TGF-beta, IL-1, and epinephrine. Furthermore, it has been recently suggested that glucocorticoids inhibit the synthesis of the enzyme by the conversion of cyclooxygenase mRNA into a cryptic, untranslatable form.