Prostaglandin Biosynthesis

Figure 19.30 outlines the biosynthesis of the 2-series (containing 2 double bonds) of prostaglandins. These reactions occur in the endoplasmic reticulum.

> 1. Arachidonic acid is released from membrane-bound phospholipids. This can occur in response to stimuli by hormones (such as bradykinin or epinephrine) or by proteases (such as thrombin). The bee venom protein melittin can also stimulate arachidonate release. The following phospholipase enzymes may be involved

> > Phospholipase A 2 may act on phosphatidylcholine or phosphatidylethanolamine to yield arachidonate.

> > Phospholipase C may act on phosphatidylinositol to yield a diacylglycerol, which is in turn cleaved to yield free arachidonate.

> 2. Arachidonate is acted on by PGH synthase, a bifunctional enzyme containing activities for a cyclooxygenase (introduces two molecules of O 2-see Figure 19.31) and another activity which involves a two-electron reduction of the peroxide formed by cyclooxygenase to give a hydroxyl group (bottom reaction in Figure 19.31).

> 3. Specific enzymes convert PGH 2 to other prostaglandins and thromboxane A 2. Some of these enzymes and the products arising from their catalysis are summarized below:

> Reductase | PGF 2
> PGH-PGD Isomerase | PGD 2
> PGH-PGE Isomerase | PGE 2
> PGI 2 synthase | PGI 2
> TxA synthase | Thromboxane A 2 (TxA 2)

See also: Eicosanoids, NSAIDs, Phospholipases

INTERNET LINK: Prostaglandin and Leukotriene Metabolism