PTGS2 (COX-2), converts arachidonic acid (AA) to<unk><unk>  H2. PTGSs are targets for NSAIDs and PTGS2 (COX-2) specific inhibitors called coxibs. PTGS-2 is a sequence homodimer. Each monomer of the enzyme has a peroxidase and a PTGS (COX) active site. The PTGS (COX) enzymes catalyze the conversion of arachidonic acid to<unk> s in two steps. First, hydrogen is abstracted from carbon 13 of arachidonic acid, and then two molecules of oxygen are added by the PTGS2 (COX-2), giving PGG2. Second, PGG2 is reduced to PGH2 in the peroxidase active site. The synthesized PGH2 is converted to<unk> s (PGD2, PGE2, PGF2α), prostacyclin (PGI2), or thromboxane A2 by tissue-specific isomerases.(Figure<unk>  While metabolizing arachidonic acid primarily to PGG2, COX-2 also converts this fatty acid to small amounts of a racemic mixture of 15-Hydroxyicosatetraenoic acids (i.e., 15-HETEs) composed of ~22% 15(R)-HETE and ~78% 15(S)-HETE stereoisomers as well as a small amount of 11(R)-HETE. The two 15-HETE stereoisomers have intrinsic biological activities but, perhaps more importantly, can be further metabolized to a major class of agents, the lipoxins. Furthermore, aspirin-treated COX-2 metabolizes arachidonic acid almost exclusively to 15(R)-HETE which product can be further metabolized to epi-lipoxins. The lipoxins and epi-lipoxins are potent anti-inflammatory agents and may contribute to the overall activities of the two COX's as well as to aspirin. COX-2 is naturally inhibited by calcitriol (the active form of Vitamin D).
Prostaglandin-endoperoxide synthase 2
Angiotensin-converting enzyme 2
Indoleamine 2,3-dioxygenase
Beta-secretase 1
Thromboxane receptor
Vitamin K epoxide reductase
Tropomyosin receptor kinase A
Phosphorylase kinase, alpha 1