Fatty acids, Polyunsaturated

Chemically, PUFAs are fatty acids containing two or more methylene-interrupted double bonds in their structure. The configuration of the double bonds in many naturally occurring unsaturated fatty acids is Z. These compounds are also referred to as cw-fatty acids or all-cA fatty acids. PUFAs containing E-configured double bonds also occur naturally. These so-called trans-fmy acids have been isolated from bovine fat and the milk of cow, goat, and ewe [15], There are four families of PUFAs, namely, the (0-9, (0-7, (0-6, and (0-3 PUFAs. Oleic acid (2) is the precursor for the (0-9 family, and palmitoleic acid (3) is the precursor 

There are several biosynthetic pathways that unsaturated fatty acids can arise from. In most organisms, the common mechanism is by desaturation of the corresponding saturated fatty acid. Desaturation of fatty acids involves a pr(x ess that requires molecular oxygen, NADH, and cyttKhrome bj. The reaction, which occurs in the endoplasmic reticulum, results in the oxidation of both the fatty acid and NADH. 

The stereospecific introduction of a Z-double bond (Kcurs by the abstraction of two vicinal pro-/ hydrogens atoms at C-9 and C-10 in a thioester (Fig. 3.3). In plants, R = ACP, while in animals and fungi, the thioester is activated as CoA. This reaction is catalyzed by stearoyl-ACP A -desaturase in plants and stearoyl-CoA A -desaturase in animals and fungi [1]. Oxygen and either NADPH or NADH as cofactors are required for both types of desaturases. 

The A -desaturase acts on fatty acyl-CoA, and C-14 to C-18 saturated fatty acyl chains are good substrates, with stearoyl-CoA being most active. A reduced pyridine nucleotide is required. The A -desaturase is dependent on the presence of molecular oxygen, which acts as an electron acceptor for two pairs of hydrogens, one from NADH and the other from the fatty acyl-CoA. 

The A -desaturase system consists of three major proteins (1) NADH-cytochrome b reductase, (2) cytochrome bj, and (3) a terminal desaturase component (Fig. 3.3). Under most circumstances, electron transport greatly exceeds the activity of the rate-limiting desaturase component. The A -desaturase contains one atom of a nonheme. 

Interconversions of the Polyunsaturated Fatty Acids 1. Interccmversions of Linoleic Add 

One type of evidence of the interconversion of the polyunsaturated acids is based upon the fact that one acid may prevent the deficiency caused by the exclusion of other essential fatty acids from the diet. Thus, Turpeinen (1938) and Smedley-MacLean and Nunn (1940) are of the opinion that linoleic acid is the precursor of arachidonic acid. The higher biopotency of arachidonic acid as compared with linoleic acid (see Section IV, 5) is explained as due to the fact that linoleate is only partially converted to arachidonic acid the comparative biopotency of linoleate is a reflection of the amount of arachidonate formed from given amounts of linoleate. 

The most convincing proof of the linoleate — arachidonate conversion is based upon balance experiments involving the content of arachidonate in the tissues when linoleate is fed, as compared with the values in control experiments. The supplementation of fat-deficient rats with corn oil (which contains linoleate but no arachidonate) was found to increase markedly the tetraenoic acid content of liver, kidney, heart, and brain (Rieckehoff et cd., 1949). Even before the availability of the spectrophoto-metric method of analysis for the polysaturated acids, Ellis and Isbell (1926a, 1926b) found evidence of the appearance of arachidonic acid in the pig upon the ingestion of linoleic acid. Nunn and Smedley-MacLean (1938), and also Smedley-MacLean and Hume (1941) both presented additional evidence of the appearance of arachidonate in fat-deficient rats following the administration of linoleate. Widmer and Holman (1950), in a study of the effects of fatty acids in the diet on the synthesis of the EFA, confirmed the transformation of linoleate to arachidonate in the rat. 

Evidence for the synthesis of arachidonic acid from linoleic acid has likewise been adduced from experiments on chickens. Thus, Reiser and 

However, it now appears that the deposition of linolenic acid in the tissues is dependent upon the species of animal. On the one hand, Ellis and Isbell (1926a,b) reported that only small amounts of trienoic acids were to be found in the case of pigs, even when they were fed large amounts of soybeans. However, Beadle et al. (1948) did find as much as 11.4% of this acid in the yellow fat of swine. Rats which had received a linseed oil diet were found to have as much as 25.6% of linolenate in their fat depots (Beadle et al., 1948) Brooker and Shorland (1950) reported that linolenate comprises as much as 17 % of the fat of pasture-fed horses. In most species, however, linolenate is absent from the depot fat. 

Whilst PUFAs can be oxidised enzymatically within cells by the above mentioned reactions involving free radicals to yield prostaglandins and leukotrienes, it is important to stress that they can also be oxidised non-enzymatically to yield a variety of carbonyls. This latter mechanism involves the formation of acyclic fatty-acyl hydroperoxides through a radical-mediated peroxidative pathway. 

Over the years it has been found that a number of PUFAs can promote the growth of many cell lines when added to cultures at low concentrations [42], Above 20-30 iM however inhibitory effects are often observed [43]. In terms of the modulation of cell growth and differentiation there have been a number 

Damage to polyunsaturated fatty acids tends to reduce membrane fluidity, which is known to be essential for the proper functioning of membranes [19]. However the precise role of such damage in contributing to reduced cell proliferation and/or cell death is still the subject of current investigation. Most of the proteins that play key roles in proliferative signal transduction actually function in a membrane environment, or in close association with membranes, and it is well established that the activity of integral membrane proteins is modulated by the lipids of the bilayer [51]. Moreover protein kinase C importantly has 

As already mentioned (see section 3.1) lipid peroxides can also break down non-enzymically to yield a variety of carbonyls, such as the hydroxyalkenals [54]. These aldehydes, and in particular 4-hydroxynonenal (HNE), can react with thiol and amino groups of nearby proteins, affecting several enzymic activities [55], These effects however appear to occur at HNE concentrations greater than 10 [lM. At low non-toxic concentrations other effects have been observed which have considerable relevance to cell proliferation. These include the stimulation of adenyl-cyclase and phospholipase C activity in liver membranes [56,57] and an inhibition of ornithine-decarboxylase activity [58] and the expression of globin genes and the protooncogene c-myc in K562 murine leukaemia cells [59]. 

Some analyses have shown that lipid peroxidation and the concentration of its breakdown products are relatively low in undifferentiated highly proliferating tumour cells [60,61 ] and it has been hypothesised that the products of lipid peroxidation such as HNE may play a central role in the down-regulation of cell proliferation. Recently the physiological levels of HNE have been reported and were found to range from 0.2 to 2.8 pM [62], These levels represent a steady-state level of HNE because it is continuously produced and rapidly catabolised by normal cells [63]. 

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Prostaglandins arise from unsaturated C20 carboxylic acids such as arachidonic acid (see Table 26 1) Mammals cannot biosynthesize arachidonic acid directly They obtain Imoleic acid (Table 26 1) from vegetable oils m their diet and extend the car bon chain of Imoleic acid from 18 to 20 carbons while introducing two more double bonds Lmoleic acid is said to be an essential fatty acid, forming part of the dietary requirement of mammals Animals fed on diets that are deficient m Imoleic acid grow poorly and suffer a number of other disorders some of which are reversed on feed mg them vegetable oils rich m Imoleic acid and other polyunsaturated fatty acids One function of these substances is to provide the raw materials for prostaglandin biosynthesis... 

Com oil s flavor, color, stabiHty, retained clarity at refrigerator temperatures, polyunsaturated fatty acid composition, and vitamin E content make it a premium vegetable oil. The major uses are frying or salad appHcations (50%) and margarine formulations (35%). 

Unfortunately, excess consumption of fatty foods has been correlated with serious human disease conditions. Effects on cardiovascular disease (95), cancer (96), and function of the immune system (97) have been shown. Numerous studies have been conducted to determine the effects of saturated, monounsaturated, and polyunsaturated fatty acids on semm cholesterol and more recently high density Hpoprotein (HDL) and low density Hpoprotein... 

Fig. 9. Saturated, monounsaturated, and polyunsaturated fatty acids in common oils, where His saturate I, monounsaturate and polyunsaturate (100).

Light and photosynthetic electron transport convert DPEs into free radicals of undetermined stmcture. The radicals produced in the presence of the bipyridinium and DPE herbicides decrease leaf chlorophyll and carotenoid content and initiate general destmction of chloroplasts with concomitant formation of short-chain hydrocarbons from polyunsaturated fatty acids (37,97). 

Food. Lecithin is a widely used nutritional supplement rich ia polyunsaturated fatty acids, phosphatidylcholine, phosphatidylethanolamine, phosphatidjhnositol, and organically combiaed phosphoms, with emulsifying and antioxidant properties (38). 

Enriched polyunsaturated fatty acids from highly refined TOFA. 

AH the bis- and tri-unsaturated prostanoids display sensitivity to atmospheric oxygen similar to that of polyunsaturated fatty acids and Hpids. As a result, exposure to the air causes gradual decomposition although the crystalline prostanoids ate less prone to oxygenation reactions than PG oils or solutions. 

Polyunsaturated fatty acids in vegetable oils, particularly finolenic esters in soybean oil, are especially sensitive to oxidation. Even a slight degree of oxidation, commonly referred to as flavor reversion, results in undesirable flavors, eg, beany, grassy, painty, or fishy. Oxidation is controlled by the exclusion of metal contaminants, eg, iron and copper addition of metal inactivators such as citric acid minimum exposure to air, protection from light, and selective hydrogenation to decrease the finolenate content to ca 3% (74). Careful quality control is essential for the production of acceptable edible soybean oil products (75). 

The prostaglandins (qv) constitute another class of fatty acids with aUcycHc structures. These are of great biological importance and are formed by i vivo oxidation of 20-carbon polyunsaturated fatty acids, particularly arachidonic acid [27400-91-5]. Several prostaglandins, eg, PGE [745-65-3] have different degrees of unsaturation and oxidation when compared to the parent compound, prostanoic acid [25151 -18-9]. 

Lipoxygenase-Catalyzed Oxidations. Lipoxygenase-1 catalyzes the incorporation of dioxygen into polyunsaturated fatty acids possessing a l(Z),4(Z)-pentadienyi moiety to yield ( ),(Z)-conjugated hydroperoxides. A highly active preparation of the enzyme from soybean is commercially available in purified form. From a practical standpoint it is important to mention that the substrate does not need to be in solution to undergo the oxidation. Indeed, the treatment of 28 g/L of linoleic acid [60-33-3] with 2 mg of the enzyme results in (135)-hydroperoxide of linoleic acid in 80% yield... 

Prostaglandin biosynthesis from C20 polyunsaturated fatty acids occurs by way of the endoperoxides PGG2 and PGH2. 

Although vegetable oils usually contain a higher proportion of nnsatnrated fatty acids than do animal oils and fats, several plant oils are actually high in saturated fats. Palm oil is low in polyunsaturated fatty acids and particularly high in (saturated) palmitic acid (whence the name palmitic). Coconut oil is particularly high in lanric and myristic acids (both saturated) and contains very few nnsatnrated fatty acids. 

Degradation of Polyunsaturated Fatty Acids Requires 2,4-Dienoyl-CoA Reductase... 

Polyunsaturated fatty acids pose a slightly more complicated situation for the cell. Consider, for example, the case of linoleic acid shown in Figure 24.24. As with oleic acid, /3-oxidation proceeds through three cycles, and enoyl-CoA isomerase converts the cA-A double bond to a trans-b double bond to permit one more round of /3-oxidation. What results this time, however, is a cA-A enoyl-CoA, which is converted normally by acyl-CoA dehydrogenase to a trans-b, cis-b species. This, however, is a poor substrate for the enoyl-CoA hydratase. This problem is solved by 2,4-dienoyl-CoA reductase, the product of which depends on the organism. The mammalian form of this enzyme produces a trans-b enoyl product, as shown in Figure 24.24, which can be converted by an enoyl-CoA isomerase to the trans-b enoyl-CoA, which can then proceed normally through the /3-oxidation pathway. Escherichia coli possesses a... 

Organisms differ with respect to formation, processing, and utilization of polyunsaturated fatty acids. E. coli, for example, does not have any polyunsaturated fatty acids. Eukaryotes do synthesize a variety of polyunsaturated fatty acids, certain organisms more than others. For example, plants manufacture double bonds between the A and the methyl end of the chain, but mammals cannot. Plants readily desaturate oleic acid at the 12-position (to give linoleic acid) or at both the 12- and 15-positions (producing linolenic acid). Mammals require polyunsaturated fatty acids, but must acquire them in their diet. As such, they are referred to as essential fatty acids. On the other hand, mammals can introduce double bonds between the double bond at the 8- or 9-posi-tion and the carboxyl group. Enzyme complexes in the endoplasmic reticulum desaturate the 5-position, provided a double bond exists at the 8-position, and form a double bond at the 6-position if one already exists at the 9-position. Thus, oleate can be unsaturated at the 6,7-position to give an 18 2 d5-A ,A fatty acid. 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

More than LOO different fatty acids are known, and about 40 occur widely. Palmitic acid (C ) and stearic acid (Cjy) are the most abundant saturated fatty adds oleic and linoleic acids (both Care the most abundant unsaturated ones. Oleic acid is monounsaturated since it has only one double bond, whereas linoleic, linolenic, and arachidonic acids are polyunsaturated fatty acids because they have more than one double bond. Linoleic and linolenic... 

CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH2CH2CH2CH2CH2CH2COH Linolenic acid, a polyunsaturated fatty acid... 

Polyunsaturated fatty acid (Section 27.1) A fatty acid that contains more than one double bond. 

Polysaccharide. 974, 1000-1001 synthesis of, 1001-1002 Polystyrene, uses of, 242 Polytetrafluoroethylene, uses of, 242 Polyunsaturated fatty acid, 1061... 

The composition of some common fets end oils. Fatty acids provide the R. R, and R" hydrocarbon residues in the general structure of a fat or oil shown in the text. Fats and oils all contain a mixture of saturated, monounsaturated. and polyunsaturated fatty acids. 

Potassium sorbate is a polyunsaturated fatty acid salt. It is used to inhibit molds, yeasts, and fungi in many foods, including cheese, wine, and baked goods. It is the potassium salt of sorbic acid. 

Osmundsen, H. Hovik, R. (1988). P-Oxidation of polyunsaturated fatty acids. Biochem. Soc. Trans. 16,420-422. 

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