PGIS, Prostacyclin synthase

Figure 23-6. Conversion of arachidonicacid to prostaglandins and thromboxanes of series 2. (PG, prostaglandin TX, thromboxane PGI, prostacyclin HHT, hydroxyheptadecatrienoate.) (Asterisk Both of these starred activities are attributed to one enzyme prostaglandin H synthase. Similar conversions occur in prostaglandins and thromboxanes of series 1 and 3.)...

PG synthesis involves four steps (Figme 2). The first two steps are common to all cells involved in prostaglandin synthesis while the final two steps are cell-specific (14-16). Release of the substrate, arachidonic acid, from membrane phospholipid stores by phospholipase is the initial event in prostaglandin synthesis, and this is followed by formation of the common PG intermediate, PGHj catalyzed by PGH synthase. At this point, rearrangement of PGH to form either stabk (PGD / Ej/ F, ) or unstable (platelet thromboxane - TxA, endothelial prostacyclin - PGy products takes place. The final step, also cell-specific, involves breakdown of the active compounds to irractive metabolites. 

Steps in prostaglandin (PG) biosynthesis PG synthesis involves four steps 1) Release of the substrate, arachidonic acid (20 4), firom membrane phospholipids by a phospholipase. 2) Formation of the common intermediate, PGHj, from arachi-donate by PGH synthase throu sequential cyclo-oxygenase and peroxidase activities, both ofwWch are present within the same enzyme. 3) Fonnation of cell-specific PG products, either "stable" (Dj, E, Fj,) or "imstable" (thromboxane, prostacyclin), by distinct enzymes formd in different cells and tissues. 4) Breakdown of active compoimds to inactive metabolites, using TxAj -> TxB, and PGI -> 6keto PGF as examples. 

Further, substituted cyclopentyloxyl radical 2 is probably a key intermediate in the biosynthesis of the human hormone prostacycline (PGI2) (3) from endoperoxide PGH2 (1) and the enzyme PGI-synthase. Intermediate 2 is trapped intramolecularly by addition to the olefinic double bond in the proximate side chain to afford, in subsequent transformations, eicosanoid 3 (Scheme 1) [7]. 

N. Matijevic-Aleksic, and K.K. Wu (2002). Human fallopian tubes express prostacyclin (PGl) synthase and cyclooxygenases and synthesize abundant PGI. 

Fig. 13.3 Arachidonic acid (AA) is metabolized by cy- (TXA ), PGEj, and prostacyclin (PGI ) by thromboxane clooxygenase (COX) to prostaglandin (PG) Gj that rear- synthase (TXAS), PGEj synthase (PGES), and prostacy-ranges to PGHj. PGHj is metabolized to thromboxane Aj clin synthase (PTGIS), respeetively...

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