PGF-synthase

A NADPH-dependent PGF, synthase activity has been partially purified from lung. Structurally, this enzyme is a member of the aldose reductase family of proteins. There is also a glutathione-dependent form of the enzyme [15]. The roles of these proteins in PGF synthesis in vivo remain to be established. 

Lacroix Pepin, N., P. Chapdelaine et al. 2013. Evaluation of the prostaglandin F synthase activity of human and bovine aldo-keto reductases AKRlAls complement AKRlBls as potent PGF synthases. Pjjjj J lMidins Otherl idMe 106 124—132. 

Aldehyde reductase converts PGH2 to PGF2C, but, unlike PGF-synthase, it has little or no activity toward PGD2 (Fig. 4.13). Also, aldehyde reductase does not cross-react with antibodies raised against PGF-synthase, indicating that despite their sequence similarities the two proteins may be enzymatically and structurally different. ... 

Fig. 4.13. The biosynthesis of PCFia may be catalyzed by either PGF-synthase (top) or aldehyde reductase activities (bottom).

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. 

Prostacyclin (PGI2) is an active and unstable metabolite (rj/2 = 3 minutes at 37°C and pH 7.5) formed from PGH2 by prostacyclin synthase. PGI2 has a double-ring structure and is converted by nonenzymatic hydrolysis to 6-keto-PGF] (Figure 18-22). 

Plane of Nutrition. The plane of nutrition alters the blood level of polyunsaturated fatty acids (mainly arachidonic acid), which are potent stimulators of PG release. These fatty acids can regulate PG production as precursors, as feedback inhibitors (1), or as competitors of arachidonic acid for PG synthase (15) however, other mechanisms of the effect of nutrition on PG release (for example, through nutrition-dependent production of metabolic hormones and growth factors) are not to be excluded (see below). Dietary fatty acids reduced ovarian and endometrial PGF synthesis, decreased ovulation rate in rats, delayed parturition in sheep and humans, and reduced embryonic mortalily in cows (15). 

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