Eicosapentaenoate

ALCOHOLS,HIGHERALIPHATIC - SURVEY AND NATURALALCOHOLS MANUFACTURE] (Vol 1) Eicosapentaenoic acid [10417-94-4]... 

Fig. 2. (a) The basis for prostaglandin nomenclature, where the letters A—F and J define principal families (b) defines the side chains for PG derived from dihomo-y-linolenic acid (c) PG2 derived from arachidonic acid and (d), PG derived from eicosapentaenoic acid. 

Detailed accounts of the biosynthesis of the prostanoids have been pubUshed (14—17). Under normal circumstances arachidonic acid (AA) is the most abundant C-20 fatty acid m vivo (18—21) which accounts for the predominance of the prostanoids containing two double bonds eg, PGE2 (see Fig. 1). Prostanoids of the one and three series are biosynthesized from dihomo-S-linolenic and eicosapentaenoic acids, respectively. Concentrations ia human tissue of the one-series precursor, dihomo-S-linolenic acid, are about one-fourth those of AA (22) and the presence of PGE has been noted ia a variety of tissues (23). The biosynthesis of the two-series prostaglandins from AA is shown ia Eigure 1. These reactions make up a portion of what is known as the arachidonic acid cascade. Other Hpid products of the cascade iaclude the leukotrienes, lipoxins, and the hydroxyeicosatetraenoic acids (HETEs). Collectively, these substances are termed eicosanoids. 

The third family of prostaglandins, based on the marine fatty acid precursor eicosapentaenoic acid, was synthesized with the help of a number of new methods designed for the introduction of the doubly unsaturated omega chain. 

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). 

Leukotriene B5 can be biosynthesized in the body from eicosapentaenoic acid, which is ingested in the form of dietary fish lipid. Synthetic LTB5 was synthesized as outlined below and found to have only 20% of the neutrophil chemotactic activity of LTB4, a fact which may be relevant to the antiinflammatory effect of dietary marine lipid. 

Cold-water frsh like salmon are rich in omega-3 fatty acids, which have a double bond three carbons in from the noncarboxyl end of the chain and have been shown to lower blood cholesterol levels. Draw the structure of 5,8,11,14,17-eicosapentaenoic acid, a common example. (Eicosane = C20H42)... 

There are three groups of eicosanoids that are synthesized from C20 eicosanoic acids derived from the essential fatty acids linoleate and a-linolenate, or directly from dietary arachidonate and eicosapentaenoate (Figure 23-5). Arachidonate, usually derived from the 2 position of phospholipids in the plasma membrane by the action of phospholipase Aj (Figure 24-6)—but also from the diet—is the substrate for the synthesis of the PG2, 1X2 series (prostanoids) by the cyclooxygenase pathway, or the LT4 and LX4 series by the lipoxygenase pathway, with the two pathways competing for the arachidonate substrate (Figure 23-5). 

Figure 9.5 Prostaglandins (PG) and leukotrienes (LT) derived from arachidonic (n - 6) and eicosapentaenoic acid...

EPA Eicosapentaenoic acid EpDIF Epithelial-derived inhibitory factor also known as epithelium/derived relaxant fector EPO Eosinophil peroxidase EPOR Erythropoietin receptor EPR Effector cell protease EPX Eosinophil protein X ER Endoplasmic reticulum ERCP Endoscopic retrograde cholangiopancreatography E-selectin Endothelial selectin formerly known as endothelial leucocyte adhesion molecule-1 (ELAM-1)... 

Omega-3 fatty acids (eicosapentaenoic acid and docosa-hexaenoic acid), the predominant fatty acids in the oil of cold-water fish, lower triglycerides by as much as 35% when taken in large amounts. Fish oil supplements may be useful for patients with high triglycerides despite diet, alcohol restriction, and fibrate therapy. This effect may be modulated thru PPAR-a and a reduction in apolipoprotein B-100 secretion. Omega-3 fatty acids reduce platelet aggregation and have... 

Selvaraj, RK and Klasing, KC, 2006. Lutein and eicosapentaenoic acid interact to modify iNOS mRNA levels through the PPAR gamma/RXR pathway in chickens and HD11 cell lines. J Nutr 136,1610-1616. 

Figure 11.1 Representative secondary metabolites produced by Streptomyces ceolicolor and other microorganisms, including aromatic polyketides actinorhodin and tetrohydroxynaphthalene (a), side-rophore desferrioxamines (b), polyunsaturated fatty acid eicosapentaenoic acid (c) and terpenoids beta-...

Peet M and Horrobin DF (2000). Eicosapentaenoic acid in the management of treatment-unresponsive schizophrenia. Journal of Psychopharmacology, 14(Suppl. 3), A63. 

Palakurthi, S. S., Fluckiger, R., Aktas, H., Changolkar, A. K., Shahsafaei, A., Hameit, S., Kilic, E., and Halperin, J. A. (2000). Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Res. 60, 2919-2925. 

Scheme 3. Biogenesis of halicholactones (25, 26) from arachidonic acid and eicosapentaenoic acid, as proposed by Niwa and coworkers [38]...

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 polyunsaturated fatty acids that are most abundant in fatty fish such as sardines, salmon, and mackerel. A diet high in EPA plus DHA or supplementation with these fish oils reduces the risk of cardiovascular mortality, reinfarction, and stroke in patients who have experienced an MI. 

Diets high in omega-3 polyunsaturated fatty acids (from fish oil), most commonly eicosapentaenoic acid (EPA), reduce cholesterol, triglycerides, LDL, and VLDL and may elevate HDL cholesterol. 

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... 

Prickett, J.D., Robinson, D.R., and Bloch, K.J., Enhanced production of IgE and IgG antibodies associated with a diet enriched in eicosapentaenoic acid, Immunology, 46, 819,1982. 

Eicosapentaenoic EPA C20 5 (n = 3) Abundant in fish oils and marine algae, present in animals... 

Lipids can be oxidized by some ROS such as hydroxyl ( OH). but not by H202, NO, or 02 - (Halliwell and Gutteridge 1999). However, both enzymatic and nonenzymatic cellular mechanisms can oxidize fatty acids. Challenging L. digitata sporophytes with lipopolysaccharides from various sources resulted in a rapid release of free fatty acids (FFAs) with a concomitant accumulation of oxidized derivatives of linolenic (08 2) and eicosapentaenoic acid (C20 5) (Kiipper et al. 2006). Other strong inducers of the oxidative burst, such as oligoguluronates, in Laminaria could induce neither the release of FFAs nor the oxylipin production. These results... 

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. 

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