Docosahexaenoic acid metabolic effects

Rao GHR, Radha E, White JG. Effect of docosahexaenoic arid on arachidonic acid metabolism and platelet function. Biochem Biphys Res Comm 1983 117 549-556... 

Powell WS, Gravelle F. (1984) Metabolism of icosapentaenoic acid and docosahexaenoic acid by fetal calf aorta and their effects on prostacyclin formation. Proc. 2nd Int. Symp. 94-100. 

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. 

Salem N Jr, Kim H-Y, Yergey JA. Docosahexaenoic acid membrane function and metabolism. In Simopoulos AP, KiferRR, Martin R, eds. The Health Effects of Polyunsaturates in Seafoods. Academic, New York, 1986, pp. 263-317. 

Dceda, L, Yoshida, H., Tomooka, M., Yosef, A., Imaizumi, K., Tsuji, H., and Seto, A. (1998) Effects of Long-Term Eeeding of Marine Oils with Different Positional Distribution of Eico-sapentaenoic and Docosahexaenoic Acid on Lipid Metabolism, Eicosanoid Production and Platelet Aggregation in Hy-percholesterolemic Rats, Lipids 33,897-904. 

Innis, SM., and Hansen, J.W. (1996) Plasma Fatty Acid Responses, Metabolic Effects, and Safety of Microalgal and Fungal Oils Rich in Arachidonic and Docosahexaenoic Acids in Healthy Adults, Am. J. Clin. Nutr. 64,159-167. 

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. ... 

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. 

Not only are 9c, t and 10t,12c-18 2 isomers metabolized differently, but they also have distinct effects on the metabolism of other fatty acids. Although both isomers resulted in a decrease in the level of arachidonic acid in liver phospholipids of rats, only the 10t,12c-18 2 induced an increase in the C22 polyunsaturated fatty acid in the hver hpids (2). Similarly, CLA supplementation (as a mixture or the 10f,12c isomer) decreased the 18 2n-6 content in hver phospholipids of hamsters (6). At the same time, docosahexaenoic acid was also decreased and a similar pattern was observed in low density lipoprotein-triacylglycerols. Feeding a mixture of CLA for 42 d induced an inaease in the long-chain n-3 fatty acids in rat liver, i.e., 22 5 and 22 6 (7). 

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... 

O Keefe, S.F., Lagarde, M., Grandgirard, A. and Sebedio, J.-L. (1990) Trans n-3 eicosa-pentaenoic and docosahexaenoic add isomers exhibit different inhibitory effects on ara-chidonic acid metabolism in human platelets compared to the respective cis fatty acids. J. Lipid Res. 31, 1241-1246. 

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). 

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