Polyenoic acids arachidonic acid

The biosynthesis of prostaglandins of the 2 series begfns with a C20 polyenoic acid, arachidonic acid, an omega-6 fatty add. (Synthesis of prostaglandins of the 1 series begins with a fatty acid with one fewer double bond.) The first step requires two molecules of oxygen and is catalyzed by an enzyme called cyclooxygenase-. 

Schnurr et al. [22] showed that rabbit 15-LOX oxidized beef heart submitochondrial particles to form phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids and induced the oxidative modification of membrane proteins. It was also found that the total oxygen uptake significantly exceeded the formation of oxygenated polyenoic acids supposedly due to the formation of hydroxyl radicals by the reaction of ubiquinone with lipid 15-LOX-derived hydroperoxides. However, it is impossible to agree with this proposal because it is known for a long time [23] that quinones cannot catalyze the formation of hydroxyl radicals by the Fenton reaction. Oxidation of intracellular unsaturated acids (for example, linoleic and arachidonic acids) by lipoxygenases can be suppressed by fatty acid binding proteins [24]. 

There are about 200 minor monoenoic, dienoic and polyenoic fatty acids in milk fat ranging in chain length from C10 to C24, and consisting of both positional and cisltrans isomers. A number have considerable nutritional significance for example, eicosapentaenoic acid (20 5,0.09%) and docosahex-aenoic acid (22 6,0.01%) are present in the metabolic pathway of the n-3 fatty acids, while arachidonic acid (20 4, 0.14%) is part of the n-6 pathway. 

Rao GHR, KidmeNP, Peiler JD, White JG. Influence of polyenoic acids on arachidonic arid metdx>lism and platdd function. In Cardiovascular Disease, Gallo L ed. New York Plenum PuUicatioits 1988. 

Biosynthesis The endoperoxides PGG2 and PGH2 are formed in the so-called arachidonic acid cascade from eicosatetraenoic acid (arachidonic acid) liberated from membrane phospholipids by phospholipase A2 (EC 3.1.1.4) (see figure under thromboxanes) under the action of cyclooxygenase. All other PG are then formed by further enzymatic reactions. In contrast to other hormones, PG are not stored in the cell but are always newly synthesized when required. The close relatives of the PG, the thromboxanes, prostacyclins, leuko-trienes, and lipoxins are also generated from eicosa-polyenoic acids in the lipoxygenase pathway. For synthesis, see Ut.. ... 

The enrichment of die C20- and C22-polyenoic acids of this type should be achieved by feeding appreciable amounts of the aII-cis-A i-Ci8-die-noic acid, a positional isomer of linoleic acid with the double bonds shifted one carbon atom toward the carboxy group. This acid, obtained by total synthesis and C -labeled at carbon atom 13, has been administered to animals (13a). In this experiment we expected the enrichment of the arachidonic acid isomer, A - -C2o-tetraenoic acid. The results. 

Arachidonic acid will not be substituted by the isomeric C2o-tetraenoic acid of the palmitoleic acid type. The C2o-polyenoic fatty acid fractions... 

Fig. 1 shows the specific activities of the different fatty acids. In fact, linoleic acid is not only converted to arachidonic acid and higher o)6 polyenoic acids but is also degraded to acetate which is incorporated into the common fatty acids. 

Early attempts at description of the changes in lipid composition included a diminished degree of unsaturation in deficient animals, indicated by a decrease of the iodine value of tissue lipids. When alkaline isomerization technique became available for measurement of polyenoic acids, the deficient animal was found to have a diminished content of dienoic acid and tetraenoic acid but an enhanced content of trienoic acid (Rieckehoff et al., 1949). Through supplementation with single fatty acids, it was discovered that 1in-oleic acid induced increases in tetraenoic acid (arachidonic acid) but that linolenic acid induced increases in pentaene and hexaene acids (Widmer Holman, 1950). These experiments prompted more elegant ones in the laboratories of Mead and Klenk in which the metabolism of linoleic acid to arachidonic acid, linolenic acid to penta-enoic and hexaenoic acids, and oleic to eicosatrienoic acid were described in detail (Mead, 1971). 

The processes reponsible of the different levels of polyenoic fatty acids in brain phosphoglycerides, and their possible differential roles in the various lipid classes are largely unknown. The selectively high levels of arachidonic acid in IPG, in the light of the special metabolic properties of this phospholipid in stimulated tissues, appear of possible significance. IPG has been shown to incorporate very actively intracerebrally injected labelled arachidonic acid (Yau Sun, 1974). The incorporation of the radioactivity in all lipid classes was constant by 40 minutes after the injection. 

Another factor which may affect polyenoic fatty acids in testes is the use of compounds which may inhibit or be competitive in metabolic reactions. Recently, it was reported by Coniglio et al. (1976) that the acetylenic analog of arachidonic acid, eicosa-5,8,11,14-tetraynoic acid (TYA), administered to rats maintained on a fat-free diet, had significant effects on the fatty acid composition of testicular lipids. The amount of arachidonic acid, of 22 5n-6 and of... 

Wood, R. Lee, T. High-performance liquid chromatography of fatty acids quantitative ansilysis of saturated, monoenoic, polyenoic and geometrical isomers, J.Chromatogr., 1983, 254, 237-246. [bulk derivatization gradient LOQ 10 ng lauric acid myristoleic acid tridecanoic acid linolenic acid myristic add arachidonic acid linoleic acid pentadecanoic acid palmitic acid oleic acid elaidic acid stearic acid heptadecanoic acid]... 

While it is sometimes convenient to categorize the polyenoic fatty acids which predominate in the phospholipids of animals and heterotropic protists as belonging to the co 6 group this can be misleading. The association of function with the structure of these fatty acids originates with the 6,9 term hypothesis of Thomasson (1953) applied to animals. The 6,9 term structure occurs in all the so-called essential fatty acids these include 18 2(9,12), 18 3(6,9,12), 20 3(8,11,14), and 20 4(5,8,11,14). Conversion of the first three to arachidonic acid has been demonstrated (Klenk and Pfluger, 1963 Stoffel, 1963), and it is thought that in mammals such as rat, the essential fatty acids other than arachidonic acid are important only inasmuch as they are arachidonic precursors the arachidonic acid is specifically required for functional phospholipids (Howard, 1964). It appears that mammals are incapable of carboxyl-directed desaturation (Wakil, 1964). It is presumably because of this that all the essential fatty acids have the 6,9 term structure in common. 

Although mammalian systems are able to desaturate fatty acids in this way, and also at the /3-carbon atom in the course of their oxidation, no mechanism exists by which double bonds can be introduced between C-9 and the CHg-terminus of the chain. This explains why the polyunsaturated (polyenoic) fatty acids, linoleic (18 2) and arachidonic (20 4), must be supplied in the diet (page 123). 

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