Arachidonic acid eicosanoid metabolites

The perturbation of the incorporation of linoleic add metabolites into mammary gland lipids by CLA metabolism may lead to the hypothesis that CLA is able to create a mild arachidonic acid deficiency condition, in particular in the mammary tissue which is composed mainly of neutral lipids. In fact, because CLA and some of its metabolites are preferentially incorporated into neutral lipids (15), unlike linoleic acid, which is instead incorporated mainly into phospholipids, the preponderance of neutral lipids in the mammary tissue renders the competition between these two fatty acids more favorable toward CLA. It has been demonstrated that mammary tumorigenesis requires essential fatty acids, and eicosanoid inhibitors are able to reduce tumor incidence in experimental models (22). CLA, likely by decreasing the supply of arachidonic acid and inhibiting eicosanoid formation through its metabolites, may counteract arachidonic acid-derived eicosanoid action. Because the decrease of arachidonic acid, CLA metabolite incorporation, TEB density, and tumor incidence correlated with the (XA dietary intake, we can speculate that TEB density could also be modulated by eicosanoids. More data are required, however, to substantiate this hypothesis and to identify which eicosanoid(s) may be responsible for such effects. 

Metabolites of arachidonic acid, including prostaglandins (PG), thromboxanes, and leukotrienes, are considered strong candidates as mediators of the inflammatory process. Steroids may exert a primary effect at the inflammatory site by inducing the synthesis of a group of proteins called lipocortins. These proteins suppress the activation of phospholipase A2, thereby decreasing the release of arachidonic acid and the production of proinflammatory eicosanoids (Fig. 60.6). 

Activated leukocytes at a site of inflammation release compounds which enhance the inflammatory response. The account below focuses on cytokines and eicosanoids (arachidonic acid metabolites) becaiase of their therapeutic implications. Nevertheless, the complexity of the response, and its involvement of other systems, is indicated by the range of mediators, which include ... 

Platelets in hypercholesterolemic patients are more susceptible to aggregation than normal subjects [72]. Aggregation is mediated by several mediators, including cyclooxygenase and lipoxygenase metabolites of arachidonic acid [73]. A deficiency of vitamin E enhanced eicosanoid production in platelets [74,75]. 

Fig. 1. The n-3/n-6 metabolic pathways. Precursors of the n-3 (18 3n-3, linolenic acid) and n-6 (18 2n-6, (/.-linoleic acid) are converted by a series of desaturation and (adding double bonds) and elongation (adding carbon atoms to the hydrocarbon backbone) reactions. Note that the same enzymes catalyze n-3 and n-6 desaturation and elongation reactions. Major metabolites are indicated. PUFAs with 20-carbon backbones (20 4n-6, arachidonic acid, and 20 5n-3, eicosapentaenoic acid) are precursors to the eicosanoids (prostaglandins, leukotrienes, thromboxanes). Docosahexaenoic acid (22 6n-3) is also indicated. Note that only a limited part of the metabolic pathway is shown in this figure.

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