Tetraenoic acid

Fig. 2. Aiachidonic acid cascade, HPETE = hydroperoxyeicosa-tetraenoic acids.

The absolute stereochemistries for both compounds were determined by CD analysis of the p-bromobenzoate derivatives. Two other eicosanoids were also isolated from whole animals [198], The trihydroxylated oxylipin 8jR,11S,12R-trihydroxyeicosa-5Z,9 ,14Z,17Z-tetraenoic acid (trioxilin A4,150) was detected in, or isolated from, five starfish species P. miniata, Dermasterias imbricata, Pycnopodia helianthoides, Culcita novaeguinea, and Nardoa tubercolata. Its structure was determined by H and 13C NMR and FAB-MS analyses of the natural product and of an acetonide derivative. The co6 analog of this compound (151) was isolated only from P. helianthoides. The relative stereochemistry in these metabolites (150, 151) was established from a comparison of NMR shifts with malyngic acid, a trihydroxylated C18 compound isolated from Lyngbya majuscula, while the absolute stereochemistry was proposed on the basis of the earlier isolation of 8R-HETE from P. miniata. 

Figure 6.17. Leukotriene formation in neutrophils. Arachidonic acid, which is released from membrane phospholipids by the action of either phospholipase A2 or diacylglycerol lipase (see Fig. 6.13), is oxygenated by 5-lipoxygenase to yield 5 hydroperoxy-6,8,11,14 eicosa-tetraenoic acid (5-HPETE). This is then converted into 5 hydroxy-6,8,11,14 eicosatetra-enoic acid (5-HETE) and leukotriene (LT) A4. LTA4 may then be enzymically converted into LTC4 and LTB4. LTB4 is the major product in activated neutrophils.

Isolation of 9-oxadeca-2,4,5,7-tetraenoic acid from Streptomyces kitasatoensis S. Omura,... 

Bilirubin, estradiol (3-OH), 2-OH-estrone, 2-OH-estradiol trans-retinoic acid, Catechol estrogens (2-OH 4-OH)15-OH-eicosa-tetraenoic acid, 20-OH-eicosa-tetraenoic acid, arachidonic acid, prostaglandin B1... 

Bauer and Remiger (1989) reported that the tetraenoic alkamides content was 0.04-0.39 mg/g root of E. purpurea and 0.09-1.51 mg/g root of E. angustifolia. The aerial parts had less than 0.01-0.3 mg/g of these alkamides in samples obtained from the United States and Europe. Rogers et al. (1998) found similar levels of tetraenoic alkamides in Australian-grown E. purpurea and E. angustifolia. Perry et al. (1997) observed that the tetraenoic alkamides accounted for 27% of the alkamides in the roots, 71% in the rhizome and 74% in the vegetative stem. These three parts are often harvested as a root and thus collectively the root system accounted for 84% of the total tetraenoic alkamides in the E. purpurea plant tissue. In the aerial parts of the plant, 64% of tetraenoic alkamides were found in the flower, and 31 and 5% were found in the reproductive stem and leaves, respectively. In E. purpurea, the tetraenoic alkamides accounted for 45 and 76% of the alkamides from the roots and aerial parts, respectively (Wills and Stuart, 1999). Additional research showed that the tetraenoic alkamides dodeca-2 , 4E, 8Z, lOZ-tetraenoic acid isobutylamide and... 

Echinacea has been used for centuries as a medicinal plant and has been promoted recently as an immunostimulant. Research from the last two decades has shown that Echinacea can enhance the immune system using in vitro and in vivo indicators. Jager et al. (2002) reported that dodeca-2E,4 , 8Z,10 yZ-tetraenoic acid isobutylamides could cross biological barriers via passive diffusion, suggesting that the alkamides may contribute to the in vivo effects noted by researchers. In contrast, conflicting results have... 

Fig. (13). The chemical structure of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide...

Mammals can insert a cts-alkene into the chain, providing that it is no further away from the carbonyl group than C9. We cannot synthesize linoleic or linolenic acids (see chart a few pages back) directly as they have alkenes at Cl 2 and Cl 5. These acids must be present in our diet. And why are we so keen to have them They are needed for the synthesis of arachidonic acid, a C20 tetraenoic acid that is the precursor for some very interesting and important compounds. Here is the biosynthesis of arachidonic acid. 

Eicosanoids, also referred to as icosanoids, are so named because of the 20-carbon constituency that identifies this class of oxygenated lipid molecules. A primary synthetic pathway for these molecules involves the phospholipase-mediated cleavage of a membrane phospholipid to produce arachidonic acid [(all-Z)-ik osa-5,8,ll,14-tetraenoic acid]. From this biologically essential intermediate fatty acid, two major subclasses of eicosanoids can be produced 1) leukotrienes, via the action of lipooxygenases, and 2) prostanoids, via the action of cyclooxygenases (COX-1 and COX-2). Examples of chemical structures for a leukotriene (Fig. la) and three types of prostanoids (Fig. Ib-d) underscore their shared arachidonate origin. 

Bushby and Whitham carried out a thorough study of the isomerization of 2,4-heptadiynoic acid (266) to 3,5-heptadiynoic acid (268), and from kinetic and spectroscopic data were able to show that the principal pathway for the isomerization involves the intermediate tetraenoic acid 267 . ... 

Lipoxygenase metabolites of arachidonic acid such as 12-hydroxyeicosa-tetraenoic acid (12-HETE) have been shown to be involved in the release of neurotiansmitters and other cellular functions (92-94). Basal generation of 12-HETE has been reported to be about 3.7-fold greater in SHR than in WKY platelets (95,96). Arachidonic acid has been shown to stimulate platelets by activating protein kinase C, by a prostaglandin-independent mechanism (97). It is possible that the lipoxygenase metabolites of arachidonic acid may also be involved in altered reactivity in hypertension. 

To date, only one study has evaluated the pharmacokinetics of the alkamides contained in the Echinacea products administered to humans (27). Subjects (n - 11) received a single oral 2.5-mL dose of the 60% ethanolic extract from E. angustifolia roots or placebo (60% ethanol). Six different alkamides were analyzed (1) Undeca-2D/Z-ene-8,10-diynoic acid isobutylamides (2) Dodeca-2D,4Z-diene-8,10-diynoic acidisobutylamide (3) Dodeca-2E-ene-8,10-diynoic acid isobutylamide (4) Dodeca-2E,4E,8Z,10E/ Z-tetraenoic acid isobutylamides (5) Dodeca-2E,4E,8Z-trienoic acid isobutylamide and (6) Dodeca-2E,4E-dienoic acid isobutylamide. The extract contained approx 2.5 mg of (4), and approx 0.5 mg of all other components. The Cmax and area under the curve (AUC) for (4) were approx 10-fold that achieved with each of the other components. Thus, despite a fivefold higher amount per dose, the 10-fold greater Cmax and AUC achieved with (4) suggest it exhibits a greater bioavailability than the other components. 

Dodeca-2 ,4E,8Z,10 ,-tetraenoic acid isobutylamide Undeca-2.E,4Z-diene-8,10-diynoic acid isobutylamide... 

Fig. 2. Biosynthetic pathways of polyunsaturated fatty acid and eicosanoid synthesis. The terminology used indicates first the number of carbons in the acyl chain, then the number of double bonds, and then the number of carbons from the methyl terminus at which the most distal double bond is located (e.g., 20 4n-3). HPETEs hydroperoxyeicosatetraenoic acids HETEs hydroxyeicosa-tetraenoic acids.

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