Linoleic acid metabolic conversion

FIGURE 26.2 Metabolic conversion of linoleic acid and a-linolenic acid to longer chain, more unsaturated fatty acids. 

According to the reports describing metabolic pathways involved in the conversion of linoleic acid to trihydroxy fatty acids, several intermediate reaction products, such as trihydroxy-, hydroperoxy-, dihydroxy-, and hydroxyepoxy-octadecenoate, were involved (Kato et al., 1984,1986). Those metabolites of linoleic acid showed distinct biological functions according to their intermediate structures, including mono-, di-, trihydroxy-octadecenoic acid, and hydroperoxy-, epoxy-forms (Kato et al., 1984 Blair, 2001 Gobel et al., 2002 Hou and Forman, 2000). In an effort to understand the overall mechanism involved in the varied biological functions of the complicated reaction metabolites of bio-converted polyunsaturated fatty acids, Kim et al. (2006) studied the oxidative activities on fish oil, of crude extracts produced by PR3 from... 

The first, important step in the bioconversion of linoleic acid into conjugated linoleic acid (CLA) is the preparation of an adequate amount of bacterial biomass with suitable physiological properties, such as the high activity of key enzymes reliable for the biotransformation. The second step is bioconversion of linoleic acid to CLA. LA conversion to CLA occurs in anaerobic conditions because the presence of oxygen promotes oxidative metabolism in some bacteria and results in lower CLA production (Ogawa et al, 2001). Many bacterial strains of Lactobacillus, Lactococcus, Streptococcus, Bifidobacteria, Propioni-bacterium, Butyrivibrio and bacterial isolated from various sources have been... 

Essential fatty acids (EFAs) are essential for the survival of humans and other mammals they cannot be synthesized in the body and, hence, have to be obtained in our diet and, thus, are essential (1-4). EFAs are an important constituent of cell membranes and confer on membranes properties of fluidity thus, they determine and influence the behavior of membrane-bound enzymes and receptors. Two types of naturally occurring EFAs exist in the body the oo-6 series derived from linoleic acid (LA, 18 2) and the oo-3 series derived from a-linolenic acid (ALA, 18 3). Both the 00-6 and the oo-3 series are metabolized by the same set of enzymes to their respective long-chain metabohtes. Although some functions of EFAs require their conversion to eicosanoids and other products, in most instances the fatty acids themselves are active. The longer-chain metabolites of LA and ALA regulate membrane function and are of major importance in the brain, retina, liver, kidney, adrenal glands, and gonads. 

Until recently, the commonly accepted pathway for the metabolic conversion of LNA (18 3n-3) to DHA (22 6n-3), and the corresponding conversion of dietary linoleic acid (18 2n-6) to 22 5n-6, involved the sequential utilization of delta 6-, 5-, and 4-desaturases along with elongation reactions (2-carbon additions) as depicted in Figure 10.2. The more recent and pioneering work of Dr. Howard... 

The metabolic pathways for synthesis of n-6 and n-3 families of polyunsaturated fatty acids from the essential fatty acids, linoleic acid (LA) (18 2 [n-6]) and a-linolenic acid (18 3 [n-3]), respectively, are showninFig. 2. Conversion of LA to arachidonic acid (AA) occurs via A6 desaturation to yield y-linolenic acid (GLA), then an elongation step to produce dihomo-y-linolenic acid (DHGL A) and A5 desaturation, to form AA. The A6 and A5 microsomal desaturases have been reported to utilize both NADH and NADPH as cofactors in vitro (Brenner 1977). Whether there is a more stringent pyridine nucleotide requirement in vivo is not known with certainty. Desaturase activities are especially abundant in the liver. 

Since AA is only a minor fatty acid in higher plants, eicosanoids are not of major importance for plant physiology. However, the oxygenation metabolites of linoleic acid and a-linolenic acid, called oxylipins [5,6], do play a role in plant defence reactions, in the formation of phytohormones and in the synthesis of cutin monomers [6,40-43]. Oxylipins constitute a family of lipids that are formed from free fatty acids by a cascade of reactions involving at least one step of dioxygen-dependent oxidation. The biosynthesis of oxylipins proceeds via a large number of metabolic pathways, most of which involve an unsaturated hydroperoxy fatty acid as intermediate (Scheme 10). Conversion of the hydroperoxide via the peroxide lyase pathway, the allene oxide pathway and the recently discovered peroxygenase pathway, leads to a complex pattern of oxidized lipid mediators. 

The administration of thyroxine to normal rats for several days produced an increase of A9 desaturation activity of liver microsomal preparations. Conversely, A6 desaturation activity decreased significantly under the hormone treatment. These results were attributed to an increase in glucose metabolism. The elongating enzyme system of linoleic acid seems to be insensitive to thyroxine. Neither the desaturation nor the elongation reactions were modified under propylthiouracil treatment of rats. 

The acids detected suggest the existence of two metabolic pathways in the conversion of linoleic acid to higher homologs. 

Fatty acid metabolism. It takes part in fat metabolism, although the exact mode of action is unknown for example, it is believed to be involved in the conversion of the essential unsaturated fatty acid, linoleic acid, to another fatty acid, arachidonic add. 

Under normal dietary conditions liver lipids contain high levels of linoleate and arachidonate but only trace or negligible amounts of other acids in this metabolic sequence. We have measured rates of both desaturation and chain elongation reactions in the linoleate sequence to determine what relationship exists between rates of conversion and the type of fatty acid found in liver lipids (Bernert Sprecher, 1975). Dietary linoleate is either incorporated into liver lipids, or as shown in Figure 1, it is desaturated to 6,9,12-18 3 at a rate of 1.0 nmole/min/mg microsomal protein. Liver lipids never contain measureable amounts of 6,9,12-18 3 even when this acid is added directly to the diet... 

In the rat the 22-carbon pentaenoic acid, derived from linoleic via arachidonic acid and 22 4, triples in concentration during sexual maturation and appears to be associated with the appearance and development of spermatids. Further testicular metabolism of the 22 5 include its oxidation to CO2, its conversion to 24-carbon polyenes and its retroconversion to arachidonic acid. 

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