Eicosapentaenoic acid metabolic effects

Yerram NR, Moore SA. Spector AA. Eicosapentaenoic acid metabolism in brain microvessel endothelium effect on prostaglandin formation.. 1 Lipid Res 1989 30 1747-1757. 

A double bond within the terminal seven carbon atoms can be present at o>-3 or co-6. y-Linolenic acid is an a>-6 EFA and a-linolenic acid an rw-3 EFA. Other co-3 EFA are eicosapentaenoic acid (EPA) and docosahexaenoic acid (EX)HA), both abundant in edible fish tissues. Vegetable oils are rich in rw-6 EFA (Table 18-4). Plants contain a-linolenic acid, which can be converted in the body to EPA and DOHA, but it is found within chloroplast membranes and not in seed oils hence, it may not be available in significant quantities in the diet. The a>-3 and o)-6 EFA have different metabolic effects (see below). Particularly rich sources of EPA are fishes (e.g., salmon, mackerel, blue fish, herring, menhaden) that live in deep, cold waters. These fishes have fat in their muscles and their skin. In contrast, codfish, which have a similar habitat, store fat in liver rather than muscle. Thus, cod liver oi I is a good source of EPA, but it also contains high amounts of vitamins A and D, which can be toxic in large quantities (Chapters 38 and 37, respectively). Shellfi.sh also contain EPA. Plankton are the ultimate source of EPA. 

It is largely accepted that a high dietary intake of poly-unsaturated fatty adds (PUFA) in the a>-3 series has beneficial effects. Recently, cellular lipid metabolism has been suggested as a target for cancer therapy. Cancer cells, compared with normal cells, seem to be vulnerable to exposure of certain polyunsaturated fatty acids (PUFAs), especially those in the o -3 series. Characteristic for these compounds are their poor abihty to be oxidized in the cell due to multiple double bonds. They are however likely to be ester-rfied to oflier Upids, and their incorporation into membrane phosphohpids will influence membrane properties such as fluidity, protein interactions and susceptibility to lipid peroxidation. The hypohpidemic properties of some (0-3 fatty acids, such as EPA, are probably e lained by an induction of mitochondrial P -oxidation that is not found after adrninistration of the non-hypolipidemic (o-3 PUFA docosahexaenoic acid (DHA)." However, both eicosapentaenoic acid (EPA) and DHA cause increased peroxisomal... 

Tetradecylthioacetic acid (TTA) is a fatty acid analogue in which a sulfur atom substitutes the P-methylene group of the alkyl chain. The analogue closely resembles normal fatty acids except that it is unable to be metabolized by P-oxidation. -3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also poorly oxidized and it has been reported that they inhibit proliferation of cancer cells in culture. Other similarities between TTA and < -3 fatty acids are induction of several enzymes involved in mitochondrial and peroxisomal P-oxidation. Moreover, they have hypotriglyceridemic effects, but TTA is much more potent than EPA. ... 

Besides lowering plasma lipids and the apparent protection in thrombosis, dietary supplements enriched in omega-3 fatty acids have proved to lower blood pressure, alter lipoprotein metabolism and dampen platelet aggregation among other beneficial effects in humans. The two components of fish oil attracting the most attention, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are still often referred to as omega-3, or n-3 fatty acids without any further distinction. Nearly all studies that have been conducted have used a mixture of EPA and DHA. It has, however, been reported that DHA are retroconverted to EPA in cultured hepatocytes," rat and man and it is, therefore, conceivable that EPA and DHA possess different metabolic properties. ... 

Morita I, Saito Y, Chang WC, Murota S (1983) Effects of purified eicosapentaenoic acid or arachidonic acid metabolism in cultured murine aortic smooth muscle cells, vessel walls and platelets. Lipids 1842-1849... 

Sesamin has been associated with the reduction of serum and liver lipids (Hirose etal., 1991,1996 Ide etal., 2001 Yasumoto etal., 2001). Hirose etal. (1991) reported that sesamin decreased lymphatic absorption of cholesterol. Sesamin was found to be a promoter of hepatic fatty acid oxidation in rats (Ashakumary et al., 1999). Addition of a 1 1 mixture of sesamin and episesamin to the diet of rats (0.1-0.5% of total diet) promoted mitochondrial and peroxisomal palmitoyl coenzyme A (CoA) oxidation rates in a dose-dependent manner. Rats fed diets containing 0.5% sesamin had 2 fold higher mitochondrial activity and 10 fold higher peroxisomal activity than rats fed non-sesamin diets. Yasumoto et al. (2001) reported similar findings when a 20% sesame seed diet was fed to rats. These authors compared two experimental sesame seed lines (0730 and 0732) with the commercial cultivar Masekin. Both experimental seed lines enhanced mitochondrial and peroxisomal fatty acid oxidation rates, and were more effective than the commercial cultivar at reducing plasma triacylglycerol levels (Yasumoto et al., 2001). A study of the effects of dietary sesamin on the hepatic metabolism of arachidonic and eicosapentaenoic acids in rats showed similar increases in hepatic mitochondrial and peroxisomal fatty acid oxidation (Sawada et al., 2001). 

Eicosapentaenoic add (Table 6) is easily incorporated into the cell membrane-bound phospholipids. It is a poor substrate for the cyclooxygenase/hydroper-oxidase enzymatic system, and only very small amounts of endproducts with three double bonds will be formed when compared with the relative effectiveness of arachidonate metabolism. In contrast, dcosapentaenoic add is a preferred substrate for product generation by the S-lipoxygenase in subcellular fractions of human and animal neutrophils [66,87], whereas docosahexaenoic add is also a markedly inferior substrate for leukotriene synthesis. Eicosapentaenoic acid appears to inhibit phospholipase activity, resulting in a decrease of aradiidonic acid release ([67] Fig. 4). Moreover, simultaneously with thromboxane A3 and prostaglandin I3 generation from eicosapentaenoic add, the synthesis of thromboxane A2 and prostacyclin (PGIj) from aradiidonic acid [47] decreases, mainly due to inhibitory effects on PGH synthase activity (Fig. 4). 

Fig. 4. Inhibitory effects of eicosapentaenoic acid and its metabolites on arachidonic acid metabolism which have been shown in in vitro systems...

Von Schacky, C. Weber, P.C. 1985. J. Clin. Invest., 76, 2446-2450. Metabolism and effects of platlet function of the purified eicosapentaenoic and docosahexaenoic acid in humans. 

Croset M, Lagarde M (1986) In vitro incorporation and metabolism of eicosapentaenoic and docosahexaenoic acids in human platelets. Effect on aggregation. Thromb Haemost 56 57-62... 

---