Linoleic acid/linoleate synthesis

In summary, the site of oleate is most likely the endoplasmic reticulum. This organelle contains, in addition, all the enzymes involved in phospholipid biosynthesis. Whether or not a specific polar lipid or an acyl-CoA or an acyl-ACP is directly or indirectly involved for linoleic synthesis remains for further investigations to clarify. There is indirect evidence suggesting that the monogalactosyldiglyceride in the outer envelope of the chloroplast may be involved in the conversion of linoleic acid to linolenic acid. Once linoleic acid and linolenate are formed, these acyl moieties must be transported to their specific sites. In the leaf cell, the principal site of these acids is the chloroplast lamellar membrane. At present, there is no direct evidence for the occurrence of polyunsaturation in these specific membranes or even in chloroplasts themselves (see Table II). Thus these acyl moieties must be presumably transferred directly or indirectly to their final site from their synthesizing site (see Section III for a discussion of transport mechanisms). 

Figure 13.13. Effect of dietary linoleic acid on synthesis of active eicosanoids and metabolism. Pathophysiological actions result from faster eicosanoid formation by increased hydroperoxide levels. From Lands etal. (1986).

Some fatty acids are not synthesized by mammals and yet are necessary for normal growth and life. These essential fatty aeids include llnoleic and y-linolenic acids. These must be obtained by mammals in their diet (specifically from plant sources). Arachidonic acid, which is not found in plants, can only be synthesized by mammals from linoleic acid. At least one function of the essential fatty acids is to serve as a precursor for the synthesis of eicosanoids, such as... 

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. 

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). 

Fatty acids have also been converted to difunctional monomers for polyanhydride synthesis by dimerizing the unsaturated erucic or oleic acid to form branched monomers. These monomers are collectively referred to as fatty acid dimers and the polymers are referred to as poly(fatty acid dimer) (PFAD). PFAD (erucic acid dimer) was synthesized by Domb and Maniar (1993) via melt polycondensation and was a liquid at room temperature. Desiring to increase the hydrophobicity of aliphatic polyanhydrides such as PSA without adding aromaticity to the monomers (and thereby increasing the melting point), Teomim and Domb (1999) and Krasko et al. (2002) have synthesized fatty acid terminated PSA. Octanoic, lauric, myristic, stearic, ricinoleic, oleic, linoleic, and lithocholic acid acetate anhydrides were added to the melt polycondensation reactions to obtain the desired terminations. As desired, a dramatic reduction in the erosion rate was obtained (Krasko et al., 2002 Teomim and Domb, 1999). 

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. 

Lie and coworkers31 reported the synthesis and NMR properties of all geometrical isomers of conjugated linoleic acids. Pure geometric isomers of conjugated linoleic acid (CLA) were prepared from castor oil as the primary starting material. Methyl octadeca-9Z, 11 /i-dienoate (36) and methyl octadeca-9Z,llZ-dienoate (38) were obtained by zinc reduction of methyl santalbate (35, methyl octadec-11 -en-9-ynoatc) and methyl... 

Figure 20.3 Essential fatty acids in the diet, production of physiological essential acids and their roles in the cell cycle. Essential fatty adds in the diet are mainly linoleic and a-linolenic but they are converted by desaturation and elongation reactions to the essential acids that are used in phospholipid formation and synthesis of eicosanoids. (For details of the elongation and desaturation reactions and eicosanoid formation, see Chapter 11.).

Ester synthesis of cholesterol linoleate. Cholesterol fatty acid ester is an important cell membrane lipids and has many applications in cosmetics, pharmaceutical and other industries. Akehoshi et aL(7) reported the ester synthesis of the cholesterol fatty acid ester with native lipase. Synthesis of the cholesterol fatty acid ester was also carried out in water-saturated n-hexane by palmitic acid-modified lipase. As shown in Table III, this system made it possible for the synthesis of the cholesterol fatty acid ester in organic solvents using the modified lipase. 

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. 

Because they are necessary precursors for the synthesis of other products, linoleate and linolenate are essential fatty acids for mammals they must be obtained from dietary plant material. Once ingested, linoleate may be converted to certain other polyunsaturated acids, particularly y-linolenate, eicosatrienoate, and arachidonate (eicosatetraenoate), all of which can... 

Two fatty acids are dietary essentials in humans (see p. 361) linoleic acid, which is the precursor of arachidonic acid, the sub strate for prostaglandin synthesis (see p. 211), and linolenic acid, the precursor of other co-3 fatty acids important for growth and development. [Note A deficiency of linolenic acid results in decreased vision and altered learning behaviors.] Arachidonic add becomes essential if linoleic acid is deficient in the diet. 

Figure 21-3 Major pathways of synthesis of fatty acids and glycerolipids in the green plant Arabidopsis. The major site of fatty acid synthesis is chloroplasts. Most is exported to the cytosol as oleic acid (18 1). After conversion to its coenzyme A derivative it is converted to phosphatidic acid (PA), diacylglycerol (DAG), and the phospholipids phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). Desaturation also occurs, and some linoleic and linolenic acids are returned to the chloroplasts. See text also. From Sommerville and Browse.106 See also Figs. 21-4 and 21-5. Other abbreviations monogalactosyldiacylglycerol (MGD), digalactosyldiacylglycerol (DGD), sulfolipid (SL), glycerol 3-phosphate (G3P), lysophosphatidic acid (LPA), acyl carrier protein (ACP), cytidine diphosphate-DAG (CDP-DAG).

Synthesis in mammalian tissues of arachidonic acid from linoleic acid. The A5 and A6 desaturases are separate enzymes and are also different from the A9 desaturase (fig. 18.16). The mechanisms, however, seem to be the same, involving cytochrome b5 and cytochrome reductase. The enzymes for elongation of unsaturated fatty acid such as 18 3 to 20 3 occur on the endoplasmic reticulum. 

The composition of the free fatty acids is also unique. In both human and pig stratum cornea, the free fatty acid fraction consists mainly of long and saturated hydrocarbon chains [44,45], Oleic and linoleic acid are the only unsaturated free fatty acids detected in the stratum corneum. There are various sterols present in human stratum corneum, of which cholesterol predominates. Cholesterol is the only major lipid class that is present in both plasma membranes and the intercellular lipid lamellae. Cholesterol is synthesized in the epidermis and this synthesis is independent of the hepatic one. A minor fraction is sulfated to... 

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