Synthases prostanoid

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). 

Figure 1. Arachidonic acid is cleaved from membrane phospholipids by the action of phospholipase kj The liberated arachidonic acid is then acted upon by prostaglandin G/H synthase to produce the unstable intermediate PGH2. PGH2 is converted to the multiple prostanoids shown by tissue specific isomerases. The resulting prostanoids then activate cell-membrane receptor which couple G proteins leading to the terminal effect designated in each of the boxes (with permission from [8]).

Prostanoids, consisting of prostaglandins (PGs) and thromboxanes (TXs), are members of the lipid mediators derived enzymatically from fatty acids. Arachidonic acid, a C2o essential fatty acid for most mammalians, is freed from the phospholipid molecule by phospholipase A2, which cleaves off the fatty acid precursor. Prostanoids are produced in a wide variety of cells throughout the body from the sequential oxidation of arachidonic acid by cyclooxygenase, PG hydroperoxidase, and a series of prostaglandin synthases (Figure 2.1). 

Figure 6.2. The biosynthesis of prostanoids from arachidonic acid. Free arachidonic acid is converted to the unstable intermediates PGG, and PGH, by cyclooxygenase (COX) enzymes. PGH, is then converted to the five primary prostanoids by specific synthases.

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. 

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