Endoperoxide prostaglandin

Studies of the biosynthesis of PGE2 from arachidonic acid have shown that all three oxygens come from O2 The enzyme involved prostaglandin endoperoxide syn tliase has cyclooxygenase (COX) activity and catalyzes the reaction of arachidonic acids with O2 to give an endoperoxide (PGG2)... 

In the next step the —OOH group of PGG2 is reduced to an alcohol function Again prostaglandin endoperoxide synthase is the enzyme responsible The product of this step IS called PGH2... 

Prostaglandin Endoperoxides. The naturally occurring endoperoxides, PGG, PGG2, PGH, and PGH2, as well as a number of their... 

Synthesis of Several Analogs of the Prostaglandin Endoperoxide PGH2... 

All prostaglandins are cyclopentanoic acids derived from arachidonic acid. The biosynthesis of prostaglandins is initiated by an enzyme associated with the endoplasmic reticulum, called prostaglandin endoperoxide synthase, also known as cyclooxygenase. The enzyme catalyzes simultaneous oxidation and cyclization of arachidonic acid. The enzyme is viewed as having two distinct activities, cyclooxygenase and peroxidase, as shown in Figure 25.28. 

Patrignani P, Panara MR, Greco A et al (1994) Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther 271 1705-1712... 

F.a.b.-m.s. has contributed to a detailed analysis of the high-mannose carbohydrate chains of prostaglandin endoperoxide synthase from sheep. Oligosaccharides released by hydrazinolysis were analyzed after N-re-acetylation and reduction. The f.a.b. data defined the compositions of the oligosaccharides, and showed that hydrazinolysis had effected a partial fission of the chitobiose core. 

To the best of our knowledge, no direct connection exists between this thermal behaviour of the model bicyclo[2.2.1] system 9 and prostaglandin endoperoxide 4,... 

In this context it must be noted that the natural prostaglandin endoperoxide 4 does give rise to malonaldehyde and 12-hydroxy-5,8,10-heptadecatrienoic acid 67 under biological conditions66 (Eq. 54), which connects with the chemistry of the... 

Doubtless attempts will now be made to prepare more sophisticated model compounds that more closely resemble the natural prostaglandin endoperoxides. Thus the influence of endo-5-allyl and/or cxo-6-vinyl groups upon the chemistry of the [2.2.1] system is clearly of interest. However, it seems likely that the next major effort in this area will involve a thorough and systematic investigation of the reactions of the first generation of bicyclic peroxides that has now been obtained. 

Christ-Hazelhof, E. Nugteren, D. H. (1979). Purification and characterisation of prostaglandin endoperoxide D-isomerase, a cytoplasmic, glutathione-requiring enzyme. Biochim. Biophys. Acta 572, 43-51. 

Tumorigenicity of tetrahydroepoxides. As yet, only Ch H -epoxide has been directly demonstrated to be tumorigenic (18). However, indirect evidence has been found in the high tumorigenicity of 3,4-dihydro BA, 9,10-dihydro BeP and 3,4-dihydrobenz[c]acridine (19-21), each of which is a likely metabolic precursor of a bay-region H -epoxide. In the case of 9,10-dihydro BeP, cis- and trans-9,10-dihydroxy -9,10,11,12-tetrahydro BeP were identified as products of metabolism of 9,10-dihydro BeP (22), and are the expected products of hydration of the epoxide. Diols are also formed from 7,8-dihydro BaP upon metabolism with prostaglandin endoperoxide synthase (23) or with rat liver homogenates (24). 

PGHS, prostaglandin endoperoxide H synthase PGI2, prostacycline synthase... 

Marcheselli, V. L. and Bazan, N. G. Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus. Inhibition by a platelet-activating factor antagonist. / Biol. Chem. 271 24794-24799,1996. 

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