Prostanoids synthase

Arachidonic acid, liberated from membrane phospholipids, can be metabolized to the five primary prostanoids, PGDg, PGE2, PGF2 , PGI and TXAg. The fet two steps in this process are catalyzed by the cyclooj gen-ase (COX) enzymes and thereafter by specific prostanoid synthases (32). An overview of prostanoid synthesis is illustrated in Fig. 6.2. 

The unstable endoperoxide PGH is transformed to the individual prostanoids by a series of specific prostanoid synthases (Figure 3). The profile and prevalence of these enzymes is tissue specific and determines the array of prostanoids produced by each type of cell (Wise et al, 2002). 

It has been observed that prostanoid profiles change in response to different stimuli. This can be explained by the coupling of the different prostanoid synthases to COX-1 and COX-2 in a tissue-specific manner (Ueno et a/., 2001). Examples include the coupling of COX-2 to PGIS in the cardiovascular system and of COX-1 to TXAS in platelets (Smith et al, 2000). 

The enzyme system responsible for the biosynthesis of PGs is widely distributed in mammalian tissues and has been extensively studied (2). It is referred to as prostaglandin H synthase (PGHS) and exhibits both cyclooxygenase and peroxidase activity. In addition to the classical PGs two other prostanoid products, thromboxane [57576-52-0] (TxA ) (3) and prostacyclin [35121 -78-9] (PGI2) (4) are also derived from the action of the enzyme system on arachidonic acid (Fig. 1). 

Herve, M., et al. (2003). Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion. Eur. J. Immunol 33, 2764-72. 

Prostanoids, which consist of prostaglandins (PCs) and thromboxanes (TXs), are biologically synthesized in the body from arachidonic acid by cyclooxygenase, PG hydroperoxydase, and a family of prostaglandin synthases (Fig. 1). They exert a variety of actions as hormones produced locally in various tissues and cells to maintain homeostasis. 

Herve, M., Angeli, V., Pinzar, E., Wintjens, R., Faveeuw, C., Narumiya, S., Capron, A., Urade, Y., Capron, M., Riveau, G. andTrottein, F. (2003) Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion. European Journal of Immunology 33, 2764-2772. 

Chintakunta VK, Akella V, Vedula MS et aL (2002) 3-0-Substituted benzyl pyrazidone derivatives as COX inhibitors. Eur J Med Chem 37 339-347 Coleman RA, Smith WL, Narumiya S (1994) VIII. International union of pharmacology classification of prostanoid receptors Properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46 205-229 Copeland RA, Williams JM, Giannaras J et al. (1994) Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proc Natl Acad Sd USA 91 11202-11206... 

Prostaglandin endoperoxide H2 synthase (PGHS) [EC 1.14.99.1] isoenzymes 1 and 2 catalyze the committed step in prostanoid synthesis via two sequential enzymatic reactions... 

The biosynthesis of prostanoids involves three important enzymatic reactions. In the case of PGE2, formation begins with the release of AA from phospholipids by phospholipase A2 (PLA2), followed by the synthesis of PGH2 by COX, and conversion of PGH2 to specific prostanoids (e.g., PGE2) by terminal PG synthases (66). 

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