Cyclic endoperoxide

Fiedor, 1. et al., Cyclic endoperoxides of beta-carotene, potential pro-oxidants, as products of chemical quenching of singlet oxygen, Biochim. Biophys. Acta Bioenerg., 1709, 1, 2005. 

These observations suggest that vitamin E may play a regulatory role in PG biosynthesis by controlling the formation of key intermediates such as hydroperoxides and cyclic endoperoxides. In these experiments, peroxidase activity associated with the PGH synthase could not be measured because of the contamination of other peroxidases like cyt P-450 hydroperoxidase in crude microsomal preparations. Our attempts to measure the differences in catalytic rates employing indomethacin were not successful. Nevertheless, it is not too unreasonable to assume that probably both activities of PGH synthase are equally affected by vitamin E deficiency, since both require heme as cofactor. 

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. 

Disubstituted peroxides are cleaved reductively by the same reagents as are used for hydroperoxides. The usual products are alcohols derived from the two substituents, but considerable selectivity is possible with some substrates. This is illustrated by the reduction of cyclic endoperoxides of the general formula (50) these compounds are available from the cycloaddition of singlet oxygen to cyclic conjugated dienes. The reduction of such compounds provides a good method of synthesis of cis-1,4-diols, which can be formed with retention of the double bond or with reduction of it (Scheme 29). It is also possible to prepare unsaturated epoxides by reduction with triphenylphosphine or other phosphorus(III) reagents. 

In polyunsaturated fatty acids with nonconjugated double bonds, O2 reacts with each C=C as if it were isolated, so it yields roughly equivalent amounts of hydroperoxides at both internal and external positions. However, if the double bonds are conjugated (e.g., natural conjugated linoleic acid or oxidized linoleic acid), cyclic endoperoxides are formed. 

Cyclooxygenase ccmtains o genase and peroxidase activities within a single polypeptide chain. The oxygenase activity catalyses the additicm of two Oj molecules to AA, giving rise to a cyclic endoperoxide, PGGj. This unstable metabolite is then... 

Defiyn G, Madiin S J, Carro as LO, et al. Familial bleeding tendency with partial platdet thrcanboxane syndietase defidency reorientation of cyclic endoperoxide metabolism. BrJHaematcd 1981 49 29-41. 

Prostacyclin and thromboxane-A are derived from arachidonic acid which is a constituent of cell walls, both platelet and endothelial. Cyclooxygenase (COX, PGH synthase), an enzyme present in cells at both sites, converts arachidonic acid to cyclic endoperoxides which are further metabolised by prostacyclin synthase to prostacyclin in the endotheliiun and by thromboxane synthase to thromboxane-A in platelets. Thus prostacyclin is principally... 

The major metabolites of arachidonic acid (Figure 18-19) arise from the 12-lipoxygenase, the 5-lipoxygenase, and the fatty acid cyclooxygenase pathway. The 5-lipoxygenase pathway yields leukotrienes, and the cyclooxygenase pathway yields cyclic endoperoxides, which are converted to PGs, TXs, and PGIs. 

Lipid peroxy radicals will react further to yield cyclic peroxides, cyclic endoperoxide and finally to form aldehydes, including malondialdehyde [77] or other end-products such as isoprostanes or pentane and ethane [78,79]. 

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... 

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. 

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