Fatty acid monounsaturated, synthesis

FIGURE 21-12 Routes of synthesis of other fatty acids. Palmitate is the precursor of stearate and ionger-chain saturated fatty acids, as well as the monounsaturated acids palmitoleate and oleate. Mammals cannot convert oleate to linoleate or a-linolenate (shaded pink), which are therefore required in the diet as essential fatty acids. Conversion of linoleate to other polyunsaturated fatty acids and eicosanoids is outlined. Unsaturated fatty acids are symbolized by indicating the number of carbons and the number and position of the double bonds, as in Table 10-1. 

Anaerobic pathway for biosynthesis of monounsaturated fatty acids in E. coli. Synthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate j8-hydroxydecanoyl-ACP is reached. At this point an apparent competition arises between the enzymes involved in saturated and unsaturated fatty acid synthesis. 

As the name anaerobic implies, the double bond of the fatty acid is inserted in the absence of oxygen. Biosynthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate /3-hydroxydecanoyl-ACP is reached (fig. 18.15). At this point, a new enzyme, /3-hydroxydecanoyl-ACP dehydrase, becomes involved. This dehydrase can form the a-j8 trans double bond, and saturated fatty acid synthesis can occur as previously discussed. In addition, this dehydrase is capable of isomerization of the double bond to a cis /3-y double bond as shown in figure 18.15. The /3-y unsaturated fatty acyl-ACP is subsequently elongated by the normal enzymes of fatty acid synthesis to yield pal-mitoleoyl-ACP (16 1A9). The conversion of this compound to the major unsaturated fatty acid of E. coli, cA-vacccnic acid (18 1A11), requires a condensing enzyme that we have not previously discussed, /3-ketoacyl-ACP synthase II, which shows a preference for palmitoleoyl-ACP as a substrate. The subsequent conversion to vaccenyl-ACP is cata-... 

By this method (Z)-monounsaturated fatty acids and esters could be obtained with an ( )-isomer content of less than 10% this stereoselectivity being however inferior to that of the commonly used acetylenic approach 55,56). However, the salt-free techniques used today in Wittig reactions allow (Z)-alkenoic acids to be synthesized with less than 2% of the ( )-isomers. Thus, Bestmann et al. prepared methyl and ethyl esters of (Z)-4,5,6,7,8,9,ll- and 13-alkenoic acids of different chain lengths 35,57 62), which served as intermediates in the synthesis of insect pheromones, both by reaction of co-alkoxycarbonyl-substituted alkyl-triphenyl-phosphonium salts with simple alkanals and of co-formylalkanoic esters with alkylidenephosphoranes. As the starting material for the synthesis of -substituted alkyl-phosphonium salts co-chloro- and -bromocarboxylic esters were used. The corresponding -substituted aldehydes can usually be obtained by ozone cleavage of suitable olefin derivatives or by oxidation of alkohols 57,58). 

Considerable recent research has defined conditions for successful use of lipases and other enzymes in numerous lipid modification reactions, including a variety of types of interesterifications (69, 71, 76). For edible applications to date, they have been employed at industrial scales for the production of (1) cocoa butter substitutes, for which disaturated, monounsaturated acylglycerols with the unsaturated fatty acid in the sn-2 position are desired (77) (2) to produce human milkfat analogues, where 2-palmitoyl acylglycerols are desired (77) (3) in the synthesis of 1,3- di-acylglycerols (78) and in the production of diacylglycerols for edible applications. These reactions employ vegetable oils as feedstocks. 

Early studies by Overath and Stumpf (P. Overath, 1964) established not only that the constituents of the avocado fatty acid synthesis system could be dissociated and reconstituted, but also that the heat stable fraction from E. coli known as acyl carrier protein (ACP) could replace the corresponding fraction from avocado. Plant ACPs share both extensive sequence homology and significant elements of three-dimensional structure with their bacterial counterparts. In plants, this small, acidic protein not only holds the growing acyl chain during fatty acid synthesis, but also is required for synthesis of monounsaturated fatty acids and plastidial glycerolipids. 

Dimerisation of monounsaturated fatty acids has been exploited to prepare monomers bearing two carboxylic functions and, after reduction, the corresponding diols [2], i.e., potential monomers for the synthesis of polyesters, polyamides, polyethers and polyurethanes incorporating long aliphatic motifs. Scheme 2.7 shows two possible mechanisms associated with this reaction (i.e., ene- or carbonation coupling), which is inevitably accompanied by further additions to give trimers and oligomers, if not carried out under finely controlled conditions. 

The increase in the saturated fatty acids (myristic and palmitic) found in lean and myristic acid in subcutaneous fat are very likely due to the inhibition of stearoyl-CoA desaturase activity, a key enzyme involved in the synthesis of monounsaturated fatty acids (MUFA) by CLA. Studies by Lee el al. (22) and Bretillon el al. (23) demonstrated that CLA isomers inhibited A9 desaturase activity, and thus this inhibition caused an inaease in the saturated fatty add content. Changes in the unsaturated fatty acid profile of subcutaneous fat could result from the increase of 18 1 and 18 2 due to the contribution of CLA 60 in the diet. CLA 60 was substituted for com in the study by Thiel-Cooper el al. (3) therefore, because CLA 60 contains high concentrations of unsaturated fatty acids, the diet would be higher in unsaturated fatty acids than a com diet alone, hi earlier work, Banni el al. (24) and Sdbedio el al. (25) suggested that... 

Apparently, the capacity of the desaturation enzyme system to convert saturated Into monounsaturated fatty acids depends on the amount of the terminal protein component and Its control Is mediated by protein synthesis and degradation (Oshlno and Sato, 1972). This fact could account for the liver s adaptability to different physiological conditions In which a definite microsomal desaturation activity Is required. Probably one of the best examples of this Is the response of the A9 desaturase enzyme to fasting and refeedlng. 

Microsomal (0-6 desaturases use cytochrome b5 as electron donor to introduce a double bond into the co-6 position of monounsaturated oleic acid to produce polyunsaturated linoleic acid. Thus microsomal -6 desaturases play a vital role in the polyunsaturated fatty acid synthesis in angiosperms. It has been estimated that these enzymes are responsible for more than 90% of the polyunsaturated fatty acid synthesis in non-photosynthetic tissues and developing seeds of oil crops (1). 

The very long chain monounsaturated fatty acids synthesized from radioactive oleoyl-CoA or malonyl-CoA were readily incorporated into the major intermediates of the Kennedypathway, i.e. phosphatidic acids and diacylglycerols. Concomitantly the synthesis of triacylglycerols containing very long chain acyl moieties occurred, which is consistent with the operation of the Kennedy pathway. 

Marinari LA, Goldfine H, Panos C. Specificity of cyclopropane fatty acid synthesis in Escherichia coli. Utilization of isomers of monounsaturated fatty acids. Biochemistry 1974 13 1978-1983... 

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