Prostaglandins cyclic endoperoxides

Arachidonic acid, which is stored as a cellular membrane phospholipid, is the precursor for series 2 prostaglandins. Aspir in selectively acetylates the hydroxyl group of a single serine residue at position 530 within the polypeptide chain of prostaglandin G/H synthase, the enzyme that converts arachidonate into prostaglandin cyclic endoperoxide. Aspirin thereby reduces the synthesis of the eicosanoids— prostaglandins, prostacyclin, and thromboxane A. 

Bowers, R., Ellis, E., Brigham, K. and Oates, J. (1983). Effects of prostaglandin cyclic endoperoxides on the lung circulation of sheep. J. Clin. Invest., 63, 131-137 Short, B.L., Miller, M.K., Stround, C.Y. and Fletcher, J.R. (1983). Comparison of the thromboxane inhibitors to cyclooxygenase inhibitors on survival in a newborn rat model for group B-streptococcal sepsis. In Samuelsson, B., Paoletti, R. and Ramwell, P. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research, Vol. 12, pp. 113-116. (New York Raven Press)... 

Non-steroidal anti-inflammatory drugs inhibit cyclooxygenase, the enzyme that limits the conversion of arachidonic acid to cyclic endoperoxide, an intermediate in prostaglandin production. This blocks the binding of agents released by the prostaglandin cascade to nociceptive receptors. 

G02A D Prostaglandins About 15 prostaglandins have been isolated from animal and humans (isolated from sperm), where they are biosynthetised from linoleic acid (from food) via arachidonic acid and a cyclic endoperoxide (from which prostacyclin and thromboxane are also formed). There are four series of prostaglandins based on the substitution pattern in the cyclopentane ring... 

AA is metabolized successively to the cyclic endoperoxide prostaglandins G (PGG) and H (PGH) (Figure 25—1) by the cyclooxygenase (COX) and hydroperoxidase (HOX) activities of the prostaglandin G/H synthases. Isomerases and synthases effect the transformation of PGH2 into terminal prostanoids distinguished by substitutions on their cyclopentane rings. 

Figure 3. The formation of hydroperoxy cyclic peroxides and prostaglandin-like endoperoxides from the 13S-hydroperoxide of linolenic acid by peroxy radical rearrangement. Structures are...

Eicosanoids are 20C biologically active compounds which derive from essential fatty acids. Arachidonic acid can be converted to a cyclic endoperoxide and this, in turn, can form prostaglandins, thromboxanes or prostacyclin. In contrast, if arachidonate is acted upon by a lipoxygenase then the leukotrienes or hydroxy fatty acids can be formed. All these eicosanoids have very potent, and often interacting, biological actions and affect almost every tissue in mammals. 

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