Eicosapentaenoic acid synthesis

Figure 12-6 Eicosapentaenoic acid synthesis pathway from alpha-linolenic acid. Note that the enzymes necessary to the process are delta-6-desaturase and delta-5-desaturase. (From http //www.asthmaworld.org/OMEGA3.htm)...

Hybridalactone, a novel marine derived eicosanoid from Laurencia hybrida, appears to be biosynthesized by a unique pathway from eicosapentaenoic acid. The synthesis of hybridalactone was carried out enantiospecifically from (+)-bicyclo[3.2.0]hept-4-ene-l-one so as to provide proof of stereochemistry (Ref. 4). 

Arachidonic acid (C20 4 n-6) is the precursor for the synthesis of prostaglandin molecules (Section 4.4.4), which have a wide range of biochemical effects on for example, the perception of pain, inflammation, blood clotting and smooth muscle contraction. Docosahexaenoic acid (DHA, C22 6) and eicosapentaenoic acid (EPA, C20 5) are both n-3 long-chain polyunsaturated fatty acids (PUFA) which have been shown to have significantly beneficial effects on intellectual development and inflammatory conditions such as asthma and cardiovascular disease. 

Mectianism of Action A combination of ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that inhibits acyl coenzyme A l,2-diacylglycerol acyltransferase and increases peroxisomal oxidation in the liver. Therapeutic Effect Reduces the synthesis of triglycerides in the liver. 

Kragballe, K., P. Voorhees, C.R. Darley, and E.J. Goetzl, Leukotriene B5 derived from eicosapentaenoic acid does not stimulate DNA synthesis of cultured human keratinocytes but inhibits the stimulation induced by leukotriene B4. J. Invest. Dermatol., 1985, 84. 

Haraldsson, G. G, Gudmundsson, B. O., and Almarsson, O. 1995. The synthesis of homogeneous triglycerides of eicosapentaenoic acid and docosahexaenoic acid by lipase. Tetrahedron, 51, 941-952. 

Fish is the most important source of the n-3-PUFAs Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and populations consuming fish have lower heart rates. Other important parameters reported were lower blood pressure and higher HDL cholesterol. The strongest evidence for an effect of n-3-fatty acids on disease is the inverse relationship between diet, blood, and tissue levels and coronary heart disease. n-3-PUFAs prevent heart disease by preventing arrhythmias, generating prostanoids and leukotrienes with anti-inflammatory actions, and inhibiting synthesis of cytokines and mitogens that provoke inflammation and promote plaque formation. ... 

Supercritical fluid carbon dioxide (SC-CO2) fractionation of fish oil ethyl esters (EE) was employed to prepare EE of two omega-3 fatty acids, all cis-5,8,11,14, 17-eicosapentaenoic acid (EPA) and all cis-4,7,10,13, 16,19-docosahexaenoic acid (DHA) in 90% purity and to separate the synthetic triacylglycerols (TG), trieicosapentaenoylglycerol (tri-EPA), and tridocosahexaenoyl-glycerol (tri-DHA) in > 92% purity from other reaction mixture components. In the synthesis, glycerine reacted with EE and sodium glyceroxide catalyst to form TG. 

Sayanova, O.V. Napier, J.A. Eicosapentaenoic acid biosynthetic routes and the potential for synthesis in transgenic plants. Phytochemistry 2004, 65 (2), 147-158. 

One important group of nutrients, rarely included in the Western diet, is the essential fatty acids. These compounds are precursors to prostaglandins, which inhibit testosterone binding in the prostate. They also act as anti-inflammatory agents and restrain protein synthesis and cell growth in the prostate. The omega-3 marine lipids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to inhibit the growth of prostatic tumors. Flax seed, a rich source of essential fatty acids, has been shown to inhibit cancer metastasis in studies done with mice. 

A diet supplemented with GLA and eicosapentaenoic acids improved oxygen delivery by decreasing vascular resistance and increasing cardiac index in endotoxin-induced lung injury in pigs. This mechanism is thought to involve attenuation of endotoxin-induced thromboxane B2 synthesis (Murray et al., 1995). A study (Mancuso et al., 1997) in endotoxic rats demonstrated that in addition to attenuation of thromboxane B2 production, production of leukotriene B4, leukotriene C/D4, and PGFla,... 

Although most hpids required for cell structure, fuel storage, or hormone synthesis can be synthesized from carbohydrates or proteins, we need a minimal level of certain dietary hpids for optimal health. These hpids, known as essential fatty acids, are required in our diet because we cannot synthesize fatty acids with these particular arrangements of double bonds. The essential fatty acids a-linoleic and a-linolenic acid are supphed by dietary plant oils, and eicosapentaenoic acid (ERA) and docosa-hexaenoic acid (DHA) are supplied in fish oils. They are the precursors of the eicosanoids (a set of hormone-like molecules that are secreted by cells in small quantities and have numerous important effects on neighboring cells). The eicosanoids include the prostaglandins, thromboxanes, leukotrienes, and other related compounds. 

According to Sim et al. (1972), there is a marked increase of oleic acid content in the egg yolk after supplements of sunflower oil in the feed. The increase of oleic acid is higher than in other feed mixtures with rape oil, soybean oil, or beef tallow. It is remarkable that with other diets low in linoleic acid, a reduction in linoleic acid content in the egg yolk does not conform to the decrease in linoleic acid in the feed. The living organism can produce linoleic acid from certain precursors (e.g., cis-2-octenoic acid), where the synthesis required for chain augmentation must be repeated five times for the production of a double bond. Although linoleic acid and linolenic acid are precursors for the production of arachidonic acid ( 20 4), docosapentaenoic acid ( 22 5), eicosapentaenoic acid ( 20 5) (EPA), and docosahexaenoic acid ( 22 5) (DHA). According to Reiser (1950), hens can produce eicosatrienoic acid ( 20 3). 

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.

Rustan, A.C., Nossen, J.O, Christiansen, E.N. Drevon, C.A. 1988. J. LipidRes. 29 1417-1426. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A 1,2-diacylglycerol acyltransferase. 

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