PharmGKB summary

The PTGS2 gene codes for prostaglandin G/H synthase-2, which catalyses the first two steps in the metabolism of arachadonic acid. Prostaglandin G/H synthase-2 has two active sites, a hydroperoxidase and a cyclooxygenase (COX) site, and is colloquially termed COX-2. The bifunctional enzyme performs the bis-dioxygenation and reduction of arachadonic acid to form prostaglandin (PG)G2 and H2. PGH2 is then converted to other PGs that modulate inflammation, including PGD2, PGE2, PGF2α, PGI2, and thromboxane A2 (This pathway is shown in the Lipid maps database at http://www.lipidmaps.org/data/IntegratedPathways Data/SetupIntegratedPathways.pl? imgsize=730&Mode=RAW2647&DataType=FAEicosanoidsMedia). COX-2 is the target for nonsteroidal anti-inflammatory drugs (NSAIDS) including those that were purposefully designed (pd) to be selective for COX-2 (pdNSAIDs or coxibs). PTGS2 is a paralog of PTGS1, which codes for the COX-1 enzyme. Although both proteins perform the same endogenous reactions, there are dramatic differences in the pattern, regulation, location, and timing of their expression that suggest crucial differences in the function. COX-1 seems to be predominantly responsible for homeostatic functions including the protection of the gastric mucosa. COX-2, in contrast, is responsible for pathogenic and inflammatory responses. These differences led to the development of selective COX-2 inhibitors to treat