9,11-Linoleic acid biological activity

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Why cis-9, trans-11 alone is found in phospholipids is unclear. However, the cis-9, trans-11 isomer exhibits a configuration that is most similar to linoleic acid (Figure 1). We have proposed that the cis-9, trans-11 isomer may be the biologically active anticarcinogenic CLA isomer. 

Pariza, M.W., Park, Y., and Cook, M.E. 2001. The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 40(4) 283-298. 

Pariza, M.W. 1999. The biological activities of conjugated linoleic acid. In Advances in Conjugated Linoleic Acid Research, Vol. 1 (M.P. Yurawecz, M.M. Mossoba, J.K.G. Kramer, M.W. Pariza, G. Nelson, eds.), pp. 12-20, AOCS Press, Champaign, IL. 

Conjugated linoleic acid (CLA) has attracted much interest recently, due its potential anti-cancer, anti-atherogenic and anti-inflammatory therapeutic properties (Weiss et al., 2004 see Chapter 3). CLA occurs as several positional and geometric isomers of Ci8 2 with a conjugated double bond. The cis-9, tram-11 CLA isomer occurs most often naturally. Commercial sources of CLA also contain the trans-10 and cis-12 isomer, which is also biologically active. Since various isomers of CLA differ in biological activity, methods of analysis for the various CLA isomers have become very... 

Since Wallen et al. (1962) reported the first bioconversion of oleic acid to 10-hydroxystearic acid by a Pseudomonad, microbial conversions of unsaturated fatty acids from different substrates by various microbial strains have been widely exploited to produce new, value-added products. Among the unsaturated fatty acids used for microbial production of hydroxy fatty acids, three (oleic, linoleic, and linolenic acids) were well studied as substrates to produce mono-, di-, and trihydroxy fatty acids. Recently, a bacterial strain Pseudomonas aeruginosa NRRL B-18602 (PR3) has been studied to produce hydroxy fatty acids from several fatty acid substrates. In this review, we introduce the production of hydroxy fatty acids from their corresponding fatty acid substrates by P. aeruginosa PR3 and their industrially valuable biological activities. 

According to the reports describing metabolic pathways involved in the conversion of linoleic acid to trihydroxy fatty acids, several intermediate reaction products, such as trihydroxy-, hydroperoxy-, dihydroxy-, and hydroxyepoxy-octadecenoate, were involved (Kato et al., 1984,1986). Those metabolites of linoleic acid showed distinct biological functions according to their intermediate structures, including mono-, di-, trihydroxy-octadecenoic acid, and hydroperoxy-, epoxy-forms (Kato et al., 1984 Blair, 2001 Gobel et al., 2002 Hou and Forman, 2000). In an effort to understand the overall mechanism involved in the varied biological functions of the complicated reaction metabolites of bio-converted polyunsaturated fatty acids, Kim et al. (2006) studied the oxidative activities on fish oil, of crude extracts produced by PR3 from... 

Figure 12.16. Omega-3 fatty acids and their relevance to prostaglandin metabolism, a Omega-3 nnsatnrated fatty acids are derived from linoleic acid by a special desatnrase fonnd in plants bnt not in mammals. They are particnlarly common in cold-waterfish. b The different nnmbers and positions of donble bonds persist in the eicosanoids derived from different fatty acid precnrsors, giving rise to different homologons derivatives. This is shown here for prostaglandin E. c Biological activity of the eicosanoids derived from eicosapentanoic acid (EPA).

Over the last two decades, the conjugated fats and, particularly, conjugated linoleic acid (CLA) have been intensively studied for their biological activity. As a result of the ease of synthesis, blends of two CLA isomers, namely 9,11-ct and 10,12-tc-CLA, have been the focus of most research into biological activity. Recent research, however, has been expanding to include pure or enriched isomer preparations. 

Conjugated linoleic acids (CLAs) have been reported to be antitumoral fatty acids [9,10]. Two types of biologically active CLAs are known the cis-9,trans-ll isomer and the trans-l0,cis-l2 isomer. The former is the principal dietary form of CLA and was used in our experiment as a reference. Comparisons of cytotoxicity to breast cancer cells revealed that the cytotoxicity of 13-MTD was almost equivalent to that of CLA. 

Palombo JD, Ganguly A, Bistrian BR, Menard MR (2002) The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells. Cancer Lett 111 163-172. 

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