Eicosapentaenoic acid function

Dietary polyunsaturated fatty acids (PUFAs), especially the n-3 series that are found in marine fish oils, modulate a variety of normal and disease processes, and consequently affect human health. PUFAs are classified based on the position of double bonds in their lipid structure and include the n-3 and n-6 series. Dietary n-3 PUFAs include a-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) whereas the most common n-6 PUFAs are linoleic acid, y-linolenic acid, and arachidonic acid (AA). AA is the primary precursor of eicosanoids, which includes the prostaglandins, leukotrienes, and thromboxanes. Collectively, these AA-derived mediators can exert profound effects on immune and inflammatory processes. Mammals can neither synthesize n-3 and n-6 PUFAs nor convert one variety to the other as they do not possess the appropriate enzymes. PUFAs are required for membrane formation and function... 

The conversion of oleoyl-CoA to linoleoyl-CoA is accomplished by some insects118 but does not take place in most animals. As a result of this biosynthetic deficiency, polyunsaturated fatty acids such as linoleic, linolenic, and the C20 arachidonic acid are necessary in the diet (Box 21-B). One essential function of linoleic acid is to serve as a precursor of prostaglandins and related prostanoids (Section D). Dietary linoleate is converted to its Co A derivative and then by sequential A6 desaturation,119 elongation, and then A5 desaturation, to the 20 4 (A5 8 11 14) arachidonoyl-CoA (Fig. 21-2, lower right). These acids are referred to as 0)6 because of the position of the last double bond. Linolenic acid can be converted in an analogous fashion to the CoA derivative of the 20 5 (A5 8 11 14 17 co6) eicosapentaenoic acid (EPA). The 22 6 docasahexaenoic acid (DHA Fig. 21-2) is apparently formed by elongation of the 22 5 acyl-CoA to 24 5, desaturation, transfer to a peroxisome or mitochondrion, and p oxidation to shorten the chain.953... 

Polyunsaturated fatty acids (PUFAs) have various physiological functions and are widely used as pharmaceuticals, neutraceuticals, and as food additives. The ethyl ester of eicosapentaenoic acid (EPA) has been used for the treatment of arteriosclerosis and hyperlipemia since 1991 in Japan (Hara, 1993). DHA possesses not only similar physiological activities to those of EPA, but also an important function in the brain and retina (Hung, 2007). In addition, DHA accelerates the growth of preterm infants as does arachidonic acid (Carlson et al., 1993 Lanting et al., 1994). From these reasons, DHA ethyl ester (DHAEE) is currently expected to be used as a medicine, and the development of the purification methods is desired. 

Swann PG, Parent CA, Croset M, Fonlupt P, Lagarde M, Venton DL, and Le Breton GC. (1990) Enrichment of platelet phospholipids with eicosapentaenoic acid and docosahexaenoic acid inhibits thromboxane A2/prostaglandin H2 receptor binding and function. J. Biot. Cheia 263,21692-21697. 

Khan et al. examined the effects of n-3 and n-6 fatty acid supplements (two of which contained OEP) on the microvascular blood flow and endothelial function in 173 healthy men and women aged 40 to 65 years in an 8-month, double-blind, randomized, placebo-controlled study. For the single OEP supplementation, the group received a total daily OEP of 5 g (which contained 400 mg/day of y-linolenic acid). For the tuna oil/OEP supplementation, the group received a total daily tuna oil of 5 g (which contained 6% of eicosapentaenoic acid and 27% of docosahexaenoic acid per day) and OEP of 5 g. Results showed that there although there were significant improvements... 

Hirai, A., Terano, T., Makuta, H., Ozawa, A., Fujita, T., Tamura, Y. and Yoshida, S. (1989) Effect of oral administration of highly purified eicosapentaenoic acid and docosahexaenoic acid on platelet function and serum lipids in hyperlipidemic patients. In Advances In Prostaglandin, Thromboxane, and Leukotriene Research, vol. 19, New York Raven Press, pp. 627-630. 

Payan, D.G., Wong, M.Y., Chernov-Rogan, T., Valone, F.H., Pickett, W.C., Blake, V.A., Gold, W.M., and Goetzl, E.J. 1986. Alterations in human leukocyte function induced by ingestion of eicosapentaenoic acid. J. Clin. Immunol. 6, 402-410. 

Furukawa K, Tashiro T, Yamamori H, Takagi K, Morishima Y, Sugiura T, et al. Effects of soybean oil emulsion and eicosapentaenoic acid on stress response function after a severely stressful operation. Ann Surg 1999 229 255-261. 

Joseph Hibbeln of the National Institutes of Health examined the levels of omega-3 fatty acids in the blood of 50 patients hospitalized after attempting suicide. Normal persons with high blood concentrations of eicosapentaenoic acid (EPA) had fewer psychological traits related to suicidal risk. He suggested "some subgroups of suicidal patients may reduce their suicidal risk with the consumption of EPA. Another study showed that dietary intake of EPA and DHA influence serotonin-related behavioral functions. 

Domergue, F., Lerchl, J., Zahringer, U., and Heinz, E. 2002. Cloning and functional characterization of Phaeodactylum tricornutum front-end desaturases involved in eicosapentaenoic acid biosynthesis. Eur. J. Biochem. 269, 4105—4113. 

Function and Gene Reference Linoleic acid a-Linoienic acid Arachidonic acid Eicosapentaenoic acid Docosahexaenoic acid... 

Fig. 2. Interplay among superoxide anion, nitric oxide, and eicosanoids in high oxidative stress. The biological function of nitric oxide in target cells is influenced by the cellular redox state. In increased oxidative stress, which results in an oxidizing environment, NO readily form free radicals, including the highly reactive peroxynitrite (OONO ). Peroxynitrite can influence eicosanoid synthesis by interfering with different enzyme systems of the arachidonic acid cascade. Increased free radicals may also catalyze nonenzymic peroxidation of membrane PUFA (e.g., arachidonic acid), resulting in increased production of isoprostanes that possess potent vasoconstrictor activity. PLA, phospholipase NO, nitric oxide NOS, nitric oxide synthase NADPH oxidase, vascular NAD(P)H oxidase 02 , superoxide anion PUFA, polyunsaturated fatty acids EPA, eicosapentaenoic acid DHA, docosahexaenoic acid COX, cyclooxygenase PGI2 synthase, prostacyclin synthase.

Eicosapentaenoic acid (EPA, 20 5n-3), docosahexaenoic acid (DHA, 22 6n-3) (Figure 4), and a-linolenic acid (ALA, 18 3n-3, rich in plant oils) are three major -3 essential fatty aeids involved in eardiovascular function and general circulation. Administration of EPA can 1) induce endothelium-independent aortic and mesenteric vasodilation via activation of K atp channels on VSMCs via EPA-derived prostanoids [27], 2) Activation of large-conductance/Ca -mediated channels (BK) on VSMCs by EPA metabolite, 17,18-EET [28]. 

Terano T, Hirai A, Hamazaki T et al. (1983) Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis 46 321-326... 

Various polyunsaturated fatty acids of nutritional interest may alter this metabolism in different ways. One way is to affect the oxygenation of arachidonic acid, a second way is to affect cell functions through their own metabolites. Among these, two fatty acids found in substantial amounts in fish fat are of particular interest. They are eicosapentaenoic acid (EPA) or 20 5 o)3 and docosahexaenoic acid (DHA) or 22 6 0)3. EPA is closely related to arachidonic acid, with an additional double bound between carbon 17 and 18. In contrast, DHA is quite different it has two additional carbons and six double bounds at different positions [4, 7, 10, 13, 16, 19]. This difference will not allow it to compete with arachidonic acid oxygenation as EPA does. 

One of the key functional roles of PUFA is as precursors to eicosanoids. Eicosanoids are a family of bioactive mediators that are oxygenated derivatives of the 20-carbon PUFA dihomo-y-linolenic, arachidonic and eicosapentaenoic acids. Eicosanoids include prostaglandins (PG) and thromboxanes (TX), which together are termed prostanoids, and leukotrienes (LT), lipoxins (LX), hydroperoxyeicosatetraenoic acids (HPETE) and hydroxyeicosatetraenoic acids (HETE). In most conditions the principal precursor for these compounds is arachidonic acid, and the eicosanoids produced from arachidonic acid sometimes have more potent biological functions than those released from dihomo-y-linolenic or eicosapentaenoic acids. The precursor PUFA is released from membrane diacylglycerophospholipids by the action of phospholipase A or from membrane phosphatidylinositol-4,5-bisphosphate by the actions of phospholipase C and a diacylglycerol (DAG) lipase (Figure 7). 

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