Polyunsaturated fatty acids prostaglandin metabolism

Watkins, B. A., Li, Y., Lippman, H. E., and Feng, S. 2003. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins, Leukot. Essent. Fatty Acids, 68, 387-398. 

As mentioned earlier that sesame lignans, especially sesamin and epi-sesamin, could influence the metabolism of polyunsaturated fatty acid and the production of prostaglandins. As prostaglandin is one of the most influential factors for mammary carcinogenesis, Hirose et al. (99) studied the effect of sesamin on dimethylbenz-anthracene (DMBA)-induced mammary cancer. Their results showed that sesamin at a dietary level of 0.2% considerably reduced the cumulative number and mean number of mammary cancer the effectiveness of sesamin was similar to a-tocopherol. 

Experiences in cat nutrition underscore the fallacy of assuming that metabolic pathways found in one species are automatically present in others. Early studies on metabolism of PUFA were conducted on rats, which have high A6 and A5 desa-turase abilities to convert linoleic acid (18 2n-6) to the prostaglandin precursors dihomo-y-linolenic acid (20 3 -6) and arachidonic acid (20 4 -6), respectively. This led to the assumption that other species can desaturate polyunsaturated fatty acids equally well. Over a period of time, it was shown that cats are not able to convert 18 2 -6 to 20 3n-6 or 20 4 -6. The NRC currently recommends the inclusion of 5 g linoleic acid and 0.2 g arachidonic acid/kg diet dry matter. 

Recently Liu and Weller [84] have reviewed the arachidonic acid metabolism in filarial parasites and other helminths. Arachidonic acid (AA) is a 20 carbon polyunsaturated fatty acid derived from dietary fatty acids. In human tissues, AA is usually present in the esterified form such as glycerolipids, phospholipids and neutral lipids. The free AA, released by phospholipases, undergoes various enzymatic oxygenations to form local mediators such as prostaglandins and leukotrienes, which are collectively known as eicosanoids (Chart 9). These eicosanoids are associated with platelet aggregation, vasodilation, leukocyte inflammatory and immune functions and cellular adhesion [85]. 

The eicosanoids are locally active hormones (autocoids) that are derived from precursor polyunsaturated fatty acids. The rate-limiting step in the synthesis of eicosanoids is the phospholipase-regulated release of arachidonic add from membranes. Arachi-donic acid metabolism may follow one of three possible pathways. In the first, the cydooxygenase- peroxidase pathway leads to the formation of the prostenoids - prostaglandins and thromboxanes. In the second, the lipoxygenase pathway yields the leuko-trienes and lipoxins. A third pathway, the cytochrome P-450 mono oxygenase pathway is also involved in the metabolism of arachidonic add. 

Fig. 6. Three irnportam oxidative pathways for the metabolism of polyunsaturated fatty acids. A. The principal steps in the formation of prostaglandin endoperoxides from arachidonic acid. B. Likely mechanism for the formation of hydroperoxy cis.trans conjugated fatly acids by autooxidalion or by lipoxygena.sc.s. In the latter case, positional as well as stereospecificity arc normally found. The formed hydroperoxides may then be enzymatically transformed into leukotrienes (not shown) or to hydroxy acids. C. The enzymatic sequence in cytochrome P-450 mediated oxygenation. The first electron is donated from NADPH via the f lavoprotein (Fp) NADPH-cytochrome-P-450-reductase. while the second electron comes either from NADPH or NADH. In this way the monooxygenase enzymes inlrrxluce one oxygen from air into the substrate.

Hawkins AJS, Widdows J, Bayne BL (1989) The relevance of whole-body protein metabolism to measured costs of maintenance and growth in Mytilus edulis. Physiol Zool 62 745-763 Henderson RJ, Bell MV, Sargent JR (1985) The conversion of polyunsaturated fatty acids to prostaglandins by tissue homogenates of the turbot, Scophthalmus maximus (L.). J Expr Mar Biol Ecol 85 93-99... 

Of the a-linolenic acid ingested some is incorporated into phosphohpids and cholesterol esters, while very Kttle is elongated and eventually converted into prostaglandins most a-linolenic acid probably is used as fuel. Of the EPA and DHA ingested most likely a greater percentage ends in eicosanoid synthesis. Therefore, different polyunsaturated fatty acids of the (o-3 series cannot be considered as similar with respect to their metabolic fate and their effects. In particular results from experiments... 

Capillary Column Gas Chromatography-Mass Spectrometry. Reference Method for the Study of Polyunsaturated Fatty Acid Metabolism. Colloq. - Inst. Natl. Sante Rech. Med. 1979 (Pub. 1980) 91(Prostaglandins Physiol. Reprod.) 145-166 CA 94 43478v... 

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