Linoleic biosynthesis

Biosynthesis of triene pheromone components with a triene double bond system that is n-3 (3,6,9-) are probably produced from linolenic acid [49]. Moths in the families Geometridae, Arctiidae, and Noctuidae apparently utilize linoleic and linolenic acid as precursors for their pheromones that must be obtained in the diet,since moths can not synthesize these fatty acids [50]. Most of the Type II pheromones are produced by chain elongation and decarboxylation to form hydrocarbons [51]. Oxygen is added to one of the double bonds in the polyunsaturated hydrocarbon to produce an epoxide [49]. 

Macrolide aggregation pheromones produced by male cucujid beetles are derived from fatty acids. Feeding experiments with labeled oleic, linoleic, and palmitic acids indicate incorporation into the macrolide pheromone component [ 117 ]. The biosynthesis of another group of beetle pheromones, the lactones, involves fatty acid biosynthetic pathways. Japonilure and buibuilactone biosynthesized by the female scarab, Anomalajaponica, involves A9 desaturation of 16 and 18 carbon fatty acids to produce Z9-16 CoA and Z9-18 CoA,hydroxylation at carbon 8 followed by two rounds of limited chain shortening and cyclization to the lactone [118]. The hydroxylation step appears to be stereospecific [118]. 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

The common fatty acids have a linear chain containing an even number of carbon atoms, which reflects that the fatty acid chain is built up two carbon atoms at a time during biosynthesis. The structures and common names for several common fatty acids are provided in table 18.1. Fatty acids such as palmitic and stearic acids contain only carbon-carbon single bonds and are termed saturated. Other fatty acids such as oleic acid contain a single carbon-carbon double bond and are termed monounsaturated. Note that the geometry around this bond is cis, not trans. Oleic acid is found in high concentration in olive oil, which is low in saturated fatty acids. In fact, about 83% of all fatty acids in olive oil is oleic acid. Another 7% is linoleic acid. The remainder, only 10%, is saturated fatty acids. Butter, in contrast, contains about 25% oleic acid and more than 35% saturated fatty acids. 

In human being, arachidonic acid is the most important precursor for the biosynthesis of eicosanoids. Arachidonic acid is formed from linoleic acid in most mammalians by desaturation and carbon elongation to dihomog-linolenic acid and subsequent desaturation. 

Studies on the biosynthesis of lactones have shown that epoxidation of unsaturated fatty acids like, e.g., linoleic and linolenic acid may represent a common pathway to oxygenated derivatives of fatty acids. Epoxy fatty acid hydrolases were identified as key enzymes that exhibit high regioselectivity and enantiose-lectivity [25, 26]. 

Li, Y. and Watkins, B.A. 1998. Conjugated linoleic acids alter bone fatty acid composition and reduce ex vivo prostaglandin E2 biosynthesis in rats fed n-6orn-3 fatty acids. Lipids 33 417-425. 

Enzyme complexes occur in the endoplasmic reticulum of animal cells that desaturate at A5 if there is a double bond at the A8 position, or at A6 if there is a double bond at the A9 position. These enzymes are different from each other and from the A9-desaturase discussed in the previous section, but the A5 and A6 desaturases do appear to utilize the same cytochrome b5 reductase and cytochrome b5 mentioned previously. Also present in the endoplasmic reticulum are enzymes that elongate saturated and unsaturated fatty acids by two carbons. As in the biosynthesis of palmitic acid, the fatty acid elongation system uses malonyl-CoA as a donor of the two-carbon unit. A combination of the desaturation and elongation enzymes allows for the biosynthesis of arachidonic acid and docosahexaenoic acid in the mammalian liver. As an example, the pathway by which linoleic acid is converted to arachidonic acid is shown in figure 18.17. Interestingly, cats are unable to synthesize arachidonic acid from linoleic acid. This may be why cats are carnivores and depend on other animals to make arachidonic acid for them. Also note that the elongation system in the endoplasmic reticulum is important for the conversion of palmitoyl-CoA to stearoyl-CoA. 

A6 9-octadecadienoate rather than linoleate. However, animals need linoleate for the biosynthesis of dihomo-y-linolenate (A81114-eicosatrienoate) and arachidonate (A5 81114-eicosatetraenoate), C20 polyunsaturated fatty acid precursors of... 

A considerable amount of knowledge has accumulated about how pheromone components are produced in female moths since the first pathway was identified some 20 years ago. It appears that most female moths produce their pheromone through modifications of fatty acid biosynthesis pathways. For moths that utilize aldehydes, alcohols, or esters biosynthesis occurs in the pheromone gland. The exceptions are those that utilize linoleic or linolenic acids, which must be obtained from the diet. However, modifications of these fatty acids occur in the gland. For moths that utilize hydrocarbons or epoxides of hydrocarbons, the hydrocarbon is produced in oenocyte cells and then transported to the pheromone gland where the epoxidation step takes place. 

J. (1987) Biosynthesis of linoleic acid in insects. Trends Biochem. Science 12, 364— 366. 

Guiet et al. (2003) demonstrated that deuterium (2H) distribution in fatty acids was non-statistical and could be related to isotopic discrimination during chain extension and desaturation. Petroselinic acid (C18 1A6) (Fig. 21.4), a fatty acid characteristic of the seeds of the Apiaceae, has been shown to be biosynthesized from palmitoyl-ACP (C16 0) by two steps, catalysed by a dedicated A4-desaturase and an elongase. The isotopic profile resulting from this pathway is similar to the classical plant fatty acid pathway, but the isotopic fingerprint from both the desaturase and elongase steps shows important differences relative to oleic and linoleic acid biosynthesis. 

The mammalian organism is unable to introduce double bonds at fatty acids, and this is probably why these families must be present in the diet. These fatty acids can be desaturated and elongated (see Chapter 19) to form derived essential fatty acids, dihomo-T-linoleic acid (20 3o>6), arachidonic acid (20 4ft)6), and eicosapentaenoic acid (20 5ft>3), the three direct precursor acids of PGs. Dihomo-r-linoleic acid, an intermediate in the biosynthesis of arachidonic acid from linoleic acid, is the precursor of PGs of the 1 series. Arachidonic acid and eicosapentaenoic acid are precursors of PGs of the 2 series and 3 series, respectively. 

In human adipose tissue, palmitoyl-CoA is usually used in the first glycerol-3-phosphate acylation reaction. The next two acyl residues are normally unsaturated fatty acids oleic acid and, less commonly, linoleic acid. Triglyceride biosynthesis is stimulated by insulin, most likely via its activation of lipoprotein lipase and its activity in moving glucose into the cells. 

Conjugated Linoleic Acid Biosynthesis and Nutritional Significance... 

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