Enzymes of Prostanoid Biosynthesis

PGH-synthase catalyzes the conversion of arachidonate to PGH2. This unstable intermediate is immediately transformed into prostaglandins, prostacyclin (PGI2) and thromboxane A2 (TXA2) through the action of specific synthases. 

Both PGH-synthase 1 and PGH-synthase 2 carry out two sequential and distinct reactions (reviewed in refs. 34 and 35). First, a cyclooxygenase activity catalyzes the incorporation of two oxygen molecules into arachidonate, resulting in the formation of PGG2 (15-hydroperoxy-9a,l la-peroxido-prostaenoic acid). Next, a peroxidase activity catalyzes the reduction of PGG2 to PGH2 

The best substrates for the cyclooxygenase activity of PGH-synthase are arachidonate (Km = 2-10 pM) and 8,11,14-eico-satrienoate. These fatty acids are both present in tissues, but arachidonate is more abundant and it is likely to be the most common substrate in vivo. By contrast, co-3 polyunsaturated fatty acids, such as eicosapentaenoate (20 5 or docosahexaenoate 

The non-steroidal drugs that are currently used in the treatment of acute and chronic inflammatory disorders exert their therapeutic effects by inhibiting the cyclooxygenase activity of both PGH-synthase 1 and PGH-synthase Cyclooxygenase inhibi- 

PGD-synthases (also known as PGH/D isomerases) are a group of enzymes that catalyze the conversion of PGH2 to PGD2, a reaction that can also occur non-enzymatically under appropriate conditions (Fig. 4.8). 

---