Linoleic dietary

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). 

Vulcain, E. et al. (2005). Inhibition of the metmyoglobin-induced peroxidation of linoleic acid by dietary antioxidants Action in the aqueous vs. lipid phase. Free Rad. Res. 39(5) 547-563. 

Unsaturated fatty acids are probably the most abundant oxidizable endogenous substrates. In the past it was erroneously believed that unsaturated fatty acids are just products of lipid peroxidation. Now, it has been shown that they have dietary origin. Family of unsaturated fatty acids includes linoleic (Ci8), arachidonic (C2o), docosahexaenoic (C22), and other fatty acids containing two, three, four, five, or six double bonds. Some acids can be in vivo converted into others for example, linoleic acid can be metabolized to linolenic and eicosa-trienoic acids [78]. 

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. 

Polyunsaturated fatty acids are characterized by a large number of C = C double bonds in their hydrocarbon chain. Stearic acid has no C = C double bonds and therefore is not unsaturated, let alone polyunsaturated. But eleostearic acid has three C = C double bonds and thus is polyunsaturated. Polyunsaturated fatty acids are recommended in dietary programs since saturated fats are linked to a high incidence of heart disease. Of the lipids listed in Table 28-2, safflower oil has the highest percentage of unsaturated fatty acids, predominately linoleic acid, an unsaturated fatty acid with two C=C bonds. 

Dietary polyunsaturated fatty acids (PUFAs), especially the n-3 series that are found in marine fish oils, modulate a variety of normal and disease processes, and consequently affect human health. PUFAs are classified based on the position of double bonds in their lipid structure and include the n-3 and n-6 series. Dietary n-3 PUFAs include a-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) whereas the most common n-6 PUFAs are linoleic acid, y-linolenic acid, and arachidonic acid (AA). AA is the primary precursor of eicosanoids, which includes the prostaglandins, leukotrienes, and thromboxanes. Collectively, these AA-derived mediators can exert profound effects on immune and inflammatory processes. Mammals can neither synthesize n-3 and n-6 PUFAs nor convert one variety to the other as they do not possess the appropriate enzymes. PUFAs are required for membrane formation and function... 

The last essential dietary components to which we will refer and which were also discovered through feeding experiments with rats, are certain unsaturated fatty acids identified as linoleic, linolenic, and arachidonic acids by Burr and Burr in 1930. The acids are required for the formation of complex lipids which are essential in membranes for the maintenance of their fluidity (Chapter 9). Deficiencies lead to a dermatitis which does not respond to additional B vitamin supplements or to oleic acid. 

Although these are termed essential fatty acids, they are, in fact, precursors for the major polyunsaturated fatty acids that have essential roles in the body but are present only in small amounts in the diet. Linoleic acid is converted, via elongation and desaturation reactions, to dihomo-y-linolenic (20 3n-6) and then to arachidonic (20 4n-6) acid. a-Linolenic is converted to eicosapentaenoic (20 5n-3) and then docosahexae-noic (22 6n-3). The pathways for formation of these latter fatty acids, from their dietary precursors, are presented in Figures 11.11 and 11.12. Full details of one pathway are provided, as an example, in Appendix 11.4. For comparison of the two pathways, they are presented side by side in Figure 11.13. 

Wan, J. M., and R. F. Grimble. Effect of dietary linoleate content on the metabolic response of rats to EscherC chia coli endotoxin. Clin Sci (Lond) 1987 72(3) 383-385. 

The relationship between diet and cancer risk is extremely complex (7). Factors that appear to enhance carcinogenesis under one set of conditions may have no effect or even inhibit carcinogenesis under different conditions (2). The link between dietary fat and cancer is complicated by many factors, in particular total calorie intake and fatty acid composition (2). Among the fatty acids that comprise lipid, only linoleic acid is clearly linked to the enhancement of carcinogenesis in rat manunary gland (5), pancreas (4) and colon (5). 

It is not certain that the presence of CLA in tissue lipids is due entirely to the production of cis-9, trans-11 as an intermediate during the biohydrogenation of linoleic acid in the rumen. However, the amount of CLA in milk (7 J) and butter (14) is positively correlated to the level of dietary linoleic acid. Some long chain fatty acid intermediates reach the small intestine and are normally absorbed and deposited into adipose tissue (75). There is seasonal variation in CLA content of milk, with the highest values occurring usually in summer (76). 

Dietary intake is of great importance. Linoleic acid (C18 2o)6) and a-linolenic acid (C18 3o)3) are the parent essential fatty acids for humans. Both fatty acids derive from vegetable oils. Higher fatty acids are then produced by chain elongation and desaturation. In addition, some of the prime essential fatty acids, AA (C20 4o)6), EPA (C20 5w3) and DHA (C22 6w3), can be obtained directly from the diet. Meat and eggs are rich in AA, whereas fish is a rich source of EPA and DHA [14]. 

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. 

Correct answer = E. Prostaglandins are synthesized from arachidonic acid. Arachidonic acid is synthesized from linoleic acid, an essential fatty acid obtained by humans from dietary lipids. The teenager would be able to synthesize all other compounds, but presumably in somewhat depressed amounts. 

The dietary precursor of the prostaglandins is the essential fatty acid, linoleic acid. It is elongated and desaturated to arachidonic acid, the immediate precursor of the predominant class of prostaglandins (those with two double bonds) in humans (Figure 17.22). [Note Arachidonic acid is released from membrane-bound phospholipids by phospholipase Ap in response to a variety of signals (Figure 17.23).]... 

Holman, R. T., Caster, W. O. and Wiese, H, F. 1964. The essential fatty acid requirement of infants and the assessment of their dietary intake of linoleate by serum fatty acid analysis. Am. J. Clin. Nutr. 14, 70-75. 

Certain polyunsaturated fatty acids are essential in the human diet (see Box 21-B). One of these, arachidonic acid (which may be formed from dietary linoleic acid), serves as a precursor for the formation of the hormones known as prostaglandins and a series of related prostanoids. Lipids of animal origin also... 

The conversion of oleoyl-CoA to linoleoyl-CoA is accomplished by some insects118 but does not take place in most animals. As a result of this biosynthetic deficiency, polyunsaturated fatty acids such as linoleic, linolenic, and the C20 arachidonic acid are necessary in the diet (Box 21-B). One essential function of linoleic acid is to serve as a precursor of prostaglandins and related prostanoids (Section D). Dietary linoleate is converted to its Co A derivative and then by sequential A6 desaturation,119 elongation, and then A5 desaturation, to the 20 4 (A5 8 11 14) arachidonoyl-CoA (Fig. 21-2, lower right). These acids are referred to as 0)6 because of the position of the last double bond. Linolenic acid can be converted in an analogous fashion to the CoA derivative of the 20 5 (A5 8 11 14 17 co6) eicosapentaenoic acid (EPA). The 22 6 docasahexaenoic acid (DHA Fig. 21-2) is apparently formed by elongation of the 22 5 acyl-CoA to 24 5, desaturation, transfer to a peroxisome or mitochondrion, and p oxidation to shorten the chain.953... 

Another important dietary source of trans fat is conjugated linoleic acid, a class of compounds collectively known as CLA. Many CLA isomers contain conjugated cis/trans and trans/trans double bonds. Interest in CLA research has increased significantly in the past few years because several cis/trans CLA isomers have been reported to exhibit different beneficial physiological effects in animal studies (Yurawecz et al., 1999). The reader is referred to a collection of analytical papers published in a dossier (Mossoba, 2001, and references therein) that details several chromatographic and spectroscopic techniques and procedures that have been successfully applied to CLA analysis. 

Riserus, U., Amer, P., Brismar, K., and Vessby, B. (2002). Treatment with dietary transl0cisl2 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 25,1516-1521. 

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