Oxygenase cyclooxygenase

Fig. 3. Mechanisms of vasocontraction and vasorelaxation in endothelial and smooth muscle cells. COX cyclooxygenase, eNOS endothelial nitric oxide synthase, HO-1 heme oxygenase-1, EET epoxyeicosatrienoic acid, EDHF endothelium-derived hyperpolariz-ing factor, PGI2 prostaglandin I2, NO nitric oxide, CO carbon monoxide, PLC phospholipase C, IP3 inositol 1,4,5-trisphosphate, DAG diacylglycerol, ER/SR endo-plasmic/sarcoplasmic reticulum, AC adenylyl cyclase, cAMP cyclic adenosine monophosphate, sGC soluble guanylyl cyclase, cGMP cyclic guanosine monophosphate.

A useful insight into the subtle differences between the catalytic sites of the two enzymes was provided by the observations that while the cyclooxygenase activities of both were inhibited by aspirin, aspirin-acetylated Cox-2 has an increased 15-oxygenase activity, which can be inhibited by some Cox inhibitors (Mancini et al., 1994 Lecomte et al., 1994). Aspirin is known to acetylate Ser-530 of Cox-1 and Ser-516 of Cox-2. Apparently, in the acetylated Cox-2 catalytic site there is still room for arachidonate to enter in an extended conformation, which permits catalysis of 15-hydroperoxyeicosatetraenoic acid formation but not of PGG2 formation. This led to the conclusion that the catalytic site of Cox-2 must be slightly larger than that of Cox-1, a conclusion later... 

Warner TD, Giuliano F, Vojnovic I et al. (1999) Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclooxygenase-2 are associated with human gastrointestinal toxicity a full in vitro analysis. Proc Natl Acad Sci USA 96 7563-7568... 

Cyclooxygenase ccmtains o genase and peroxidase activities within a single polypeptide chain. The oxygenase activity catalyses the additicm of two Oj molecules to AA, giving rise to a cyclic endoperoxide, PGGj. This unstable metabolite is then... 

MOA Analgesic Inhibit prostaglandin synthesis by decreasing activity of cyclo-oxygenase Decrease prostaglandin synthesis by decreasing activity of cyclooxygenase-2... 

COX-2 [Cyclo-oxygenase-2] An enzyme that catalyzes the synthesis of prostaglandins from the polyunsaturated fatty acid arachidonic acid. COX-2 is responsible for the production of prostaglandins attributable to stimulation (i.e., levels are induced in times of inflammation). Cyclooxygenase activity is inhibited by aspirin-like drugs, accounting for their anti-inflammatory effects. 

Prostaglandin H synthase is the first enzyme involved in the arachidonic acid cascade . The prostaglandins can cause both relaxation and tension in smooth muscle and so have vital physiological roles. Prostaglandin H synthase acts as both a peroxidase and an oxygenase its so-called cyclooxygenase activity involves addition of two equivalents of oxygen to a free radical derived from arachidonic acid to form an endoperoxide... 

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