9- hydroxy-octadecadienoic acid

Arachidonic acid metabolites Leukotriene B4 (LTB4), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, and 13-hydroxy octadecadienoic acid (HODE)... 

HETE. The 15-lipoxygenase (15-LOX) has been the most extensively characterized pathway in the reticulocytes, leukocytes, and airway epidermal cells (24-27). An outline in Figure 5 shows that 15-LOX can, on the one hand, catalyze the abstraction of a proton from C-13 of 20-carbon AA to produce 155-hydroperoxyeicosatetraenoic acid (155-HPETE), whereas on the other hand, the 18-carbon linoleic acid is converted mainly to 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 9-hydroperoxy-10,12- , Z-octadecadienoic acid (9-HPODE) in the ratio of 10 1 (28). Both the 155-HPETE (intermediate) from AA and 13-HPODE (intermediate) from linoleic acid can be further metabolized by glutathione peroxidase to mainly monohydroxylated 15S-HETE and 13-hydroxy-octadecadienoic acid (HODE), respectively. 

In addition to 8-DOX products, G. graminis or its cell-free extracts can metabolize a variety of fatty acids into oxylipins. Of those substrates, the most interesting are linoleic and oleic acids, which are common in ascomycetes. Linoleic acid gives rise to 16-hydroxyoctadecadienoic acid and 17-hydroxyoctadecadienoic acid via cyt P-450 activity. 8,16-Dihydroxyoctadecadienoic acid and 8,17-hydroxy-octadecadienoic acid were also produced, apparently by a combination of 8-DOX and cyt P-450 activity [6,16]. 

Henry DY, Gueritte-Voegelein F, Insel PA, Ferry N, Bouguet J, Potier P, Hanoune J. Isolation and characterization of 9-hydroxy- 10-trans,12-cis-octadecadienoic acid, a novel regulator of platelet adenylate cyclase from Glechoma hederacea L. Labiatae. Eur J Biochem 1987 170 389-394. 

Hydroxy-10,12-octadecadienoic acid, which is formed by the reduction of 9-HPODE, was identified in the erythrocyte membrane phospholipid of diabetic patients [83]. It was suggested that this compound was formed as a result of glucose-induced oxidative stress in the reaction of hydroxyl radicals with linoleic acid. 

It follows from the above that MPO may catalyze the formation of chlorinated products in media containing chloride ions. Recently, Hazen et al. [172] have shown that the same enzyme catalyzes lipid peroxidation and protein nitration in media containing physiologically relevant levels of nitrite ions. It was found that the interaction of activated monocytes with LDL in the presence of nitrite ions resulted in the nitration of apolipoprotein B-100 tyrosine residues and the generation of lipid peroxidation products 9-hydroxy-10,12-octadecadienoate and 9-hydroxy-10,12-octadecadienoic acid. In this case there might be two mechanisms of MPO catalytic activity. At low rates of nitric oxide flux, the process was inhibited by catalase and MPO inhibitors but not SOD, suggesting the MPO initiation. 

Strain ALA2 converted y-linolenic acid (18 3 all ds-6,9,12) to several products including 12,17 13,17-diepoxy-6,9-octadecadienoic acid 12,13,17-trihydroxy-6(Z),9(Z)-octadecadienoic acid and 12-hydroxy-13,16-epoxy-6(Z),9(Z)-octadecadienoic acid as depicted in the top half of Figure 16.2 (Hosokawa et al, 2003a). Strain ALA2 also converted the substrate arachidonic acid (20 4 all civ-5,8,11,13) to cyclic and trihydroxyl fatty acids as reported previously (Hosokawa et al., 2003a). These reactions resulted in compounds 14,19 15,19-diepoxy-5(Z),8(Z),ll(Z)-eicosatrienoic acid 14-hydroxy-15,18-epoxy-5(Z),... 

I3-hydroperoxy-9-cis, I I-tmrw-octadecadienoic acid 9-hydroperoxy-I0-tmrw,I2 cis octadecadienoic acid 9-hydroxy-I0-fmn, I2,I3 cw-epoxyoctadecadienoic acid 9,10 -cis-epoxy-ll-trans-13 hydroxyoctadecadienoic acid... 

Synthesis of CLA by Dehydration of Ricinoleic Acid (12-Hydroxy-c/s-9-Octadecadienoic Acid)... 

Scheme 8 Generation of 13-oxo-9,ll-octadecadienoic acid and 13-oxo-9-hydroxy-10-octadecenoic acid.

When, however, 13(S)-HPOD was incubated with an ammonium sulphate precipitate of defatted com germ, the resulting 12-oxo-PDA was not optically pure but a mixture of enantiomers in a ratio of 82.18 [35]. The 12-oxo-PDA obtained by incubation of 13(S)-HPOT with flaxseed extracts was found to be a racemic mixture [36]. These results may be due to low or absent allene oxide cyclase activity in the preparations used [34]. The allene oxide cyclase, a novel enzyme in the metabolism of oxygenated fatty acids was partially characterised and found to be a soluble protein with an apparent molecular weight of about 45 kDa which catalysed specifically the conversion of allene oxide into 12-oxo-PDA [34]. The allene oxide was very unstable and was rapidly hydrolysed in aqueous media into stable 12-oxo-13-hydroxy-9(z),15(z)-octadecadienoic acid (a-ketols) [34]. 

Octadecadienoic acid, 18-hydroxy-, (Z,Z)-57-11-4 Octadecanoic acid stearic acid ... 

The production requires 2 fermentations. In the first fermentation, lipase enzymes liberate the unsaturated fatty acids of flaxseed oil. During the first feraientation, the hydrolyzed fatty acids, linolenic acid, linoleic acid and oleic acid, are converted to (respectively) 10-hydroxy-12(Z),15(Z)-octadecadienoic acid, 10-hydroxy-12(Z)-octadecenoic acid and 10-hydroxydecanoic acid by Pseudomonas sp. NRRL-2994. Pseudomonas sp. produced stereochemically pure d (R)-isomers of each of the hydroxy fatty acids (>95.8%) 23) at a concentration of >12 g/L in the fermentation broth. The resulting hydroxy fatty acids were recovered by phase separation technique, and used for the second fermentation. 

Hydroxy-13,16-epoxy-6(Z),9(Z)-octadecadienoic acid 14-Hydroxy-15,18-epoxy-5(Z),8(Z),11 (Z)-eicosatrienoic acid... 

The role of unsaturated fatty acids in inducing an inflammatory response of the endothelium has been explored and the results are contradictory (71-73). In one study, unsaturated fatty acids, by inducing an oxidative stress-like state, did promote an inflammatory response (71). However, this study could not have observed an anti-inflammatory effect because cells were not exposed to (proinflammatory) cytokines. Indeed, unsaturated fatty acids reduce the inflammatory response to cytokines in endothelial cells in vitro (72). 13-Oxo-octadecadienoic acid inhibits the cytokine-de-pendent expression of inducible cyclooxygenase in macrophages (74). As a result, the resolution of inflammation of the arterial wall would be impaired and this would favor atherosclerosis. By contrast, 13-hydroxy-octadecadienoic and 15-hydroxy-eicosatrienoic acids inhibit the cytokine-induced... 

Strain DS5 converted a-linolenic acid to 10-hydroxy-12,15-octadecadienoic acid and a minor product 10-keto-12,15-octadecadienoic acid (24). Strain DS5 also con-... 

More recently, Koritala and Bagby (28), using washed resting cells suspension of Nocardia cholestewlicum under anaerobic conditions, reported the hydration of linoleic and linolenic acids to 10-hydroxy-12(Z)-octadecenoic (5ueld 71%) and 10-hydroxy-12(Z),15(Z)-octadecadienoic acids (yield 77%), respectively. The production of 10-hydroxy fatty acids by hydratase from various microbes is summarized in Table 1. 

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