Eicosanoids modification

The pathway for the synthesis of dipalmitoyl-phos-phatidylcholine is illustrated in figure 19.5. The starting species of phosphatidylcholine is made by the CDP-choline pathway (see fig. 19.4). The fatty acid at the sn-2 position, which is usually unsaturated, is hydrolyzed by phospholi-pase A2, and the lysophosphatidylcholine is reacylated with palmitoyl-CoA. This modification permits alteration of the properties of the phospholipid without resynthesis of the entire molecule, a strategy called remodeling. Deacylation-reacylation of phosphatidylcholine occurs in other tissues and provides an important route for alteration of the fatty acid substituents at both the sn-1 and sn-2 positions. For example, fatty acids at the sn-2 position can be replaced by arachidonic acid, which is stored there until needed for eicosanoid biosynthesis, as we discuss later in this chapter. 

Apparently, parasitic flatworms have discarded some pathways of de novo lipid synthesis, but have selectively retained several biosynthetic pathways that modify host lipids. Although lipids like fatty acids and cholesterol are obtained from the host, less abundant lipids that are more difficult to acquire because of their low concentration in the host (e.g. specific unsaturated fatty acids, eicosanoids, ecdysteroids and quinones) are synthesized de novo by the parasite, usually by the modification of more abundant substrates. In this way, lipid metabolism of parasitic flatworms is adapted to an opportunistic way of life, just like their energy metabolism. 

Fischer, M.A. and Black, H.S., Modification of membrane composition, eicosanoid metabolism, and immunoresponsiveness by dietary omega-3 and omega-6 fatty acid sources, modulators of ultraviolet-carcinogenesis, Photochem. Photobiol., 54, 381, 1991. 

Berry, E.M., Hirsch, J., Most, J., McNamara, D.J., and Cunningham-Rundles, S. 1987. Dietary fat, plasma lipoproteins, and immune function in middle-aged American men. Nutr. Cancer 9, 129-142. Blair, I.A., Prakash, C., Phillips, M.A., Dougherty, R.M., and Iacono, J.M. 1993. Dietary modification of omega 6 fatty acid intake and its effect on urinary eicosanoid excretion. Am. J. Clin. Nutr. 57, 154-160. 

Complex interactions and displacements of the omega-3 and omega-6 fatty acids take place in plasma and cellular lipids after dietary manipulations. Early steps of cell activation, such as generation of inositol phosphates, are induced by dietary fatty acids (Galli et al., 1989). The effects of dietary fatty acids on the inositol phosphate pathway indicate that diet-induced modifications of PUFA at the cellular level affect the activity of the enzymes responsible for the generation of lipid mediators in addition to the formation of products (eicosanoids) directly derived from their fatty acid precursors. This shows that dietary fats affect key processes in cell function. 

The anti-inflammatory mechanism of the NSAIDs is principally related to any or all of the following three factors the inhibition of different enzymes implicated in the arachidonic acid metabolism, the modification of the effects of relevant mediators, and the inhibition of the tissue damage produced by free radicals. It is thought that the phenomenon of overexpression of the enzymes implicated in inflammation may be avoided by the effect of apoptotic mechanisms on inflammatory cells. The role of eicosanoids and NSAIDs, with either a positive or negative... 

Eicosanoids and Immune Function in the Aged Dietary Modification... 

---