20-Hydroxyeicosatetraenoic acid

The hydroperoxides obtained on thermal oxidation of cholesteryl acetate (191e) can be selectively separated by SPE and elution with a polar solvent. After reduction to the corresponding alcohols by NaBH4 and further derivatization to the trimethylsilyl ether, the products can be subjected to GLC with ion-trap MS detection. It can be thus demonstrated with the aid of standards that under the oxidation conditions (160 °C for 90 min) only the 7-position is attacked, leading to the la- and 7/3-hydroperoxy derivatives, while the plausible 4-position remains unscathed . Treatment of erythrocite ghosts with t-BuOOH causes a manyfold content increase of 5-hydroxyeicosatetraenoic acid (5-HETE), 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 5-oxoeicosatetraenoic acid (5-oxo-ETE) residues of phospholipids. These acids can be separated by HPLC, identified and quantitized by tandem MS . ... 

In addition to inflammation, another potential role for natural COX and LOX dual inhibitors is in the prevention and treatment of cancers [80], Over expression of COX-2 has been demonstrated in various different human malignancies. COX-2 inhibitors have also been shown to be efficacious in the treatment of animal models of skin, breast and bladder tumors. While the mechanism of action remains to be completely defined, the over expression of COX-2, in excess of production of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid (5-HETE) have been shown to inhibit apoptosis and increase the invasiveness of tumerogenic cell types [81,82]. It is probable that the enhanced production of PGE2 and 5-HETE promotes cellular proliferation, and consequently, increases angiogenesis [83]. 

Also extracted from native HZ were polar hydroxylated fatty acids derived presumably from cellular arachidonic and linoleic acids. Native HZ was purified from infected RBCs by a series of centrifugation steps followed by organic extraction of its lipid coat. Analysis of the lipid coat revealed the presence of hydroxylated polyunsaturated fatty acids. These polar lipids were separated using reverse phase-, normal phase-, and chiral phase high performance liquid chromatography and subsequently examined by GC-MS. Native FIZ lipid coat GC-MS analysis revealed the presence of 15-, 12-, 11-, 9-, 8-, and 5-hydroxyeicosatetraenoic acids (HETEs) as well as 13- and 9-hydroxyoctadecadienoic acids (HODEs) (35). 

Cyclopropanation of 1-oxy-1,3-dienes is not regioselective . However, certain homofuran derivatives can yield highly electrophilic dienes as demonstrated in equation 86 . This reaction has served as one of the basic steps in a synthesis of the arachidonic acid metabolite 5-HETE (5-hydroxyeicosatetraenoic acid) . 

Arachidonic acid lipoxygenases are involved in the synthesis of biomodulators which are strictly related to various diseases allergy, inflammation, atherosclerosis and cancer [77]. 5-Lipoxygenase catalyzes the first step of reactions leading to 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriens responsible for inflammatory and allergic responses. 12-Lipoxygenase catalyzes the formation of 12-HETE, involved in atherosclerosis and tumor metastasis [76]. 

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

Ogletree, M.L., Dates, J.A., Brigham, K.L. and Hubbard, W.C. (1982). Evidence for pulmonary release of 5-hydroxyeicosatetraenoic acid (5-HETE) during endotoxemia in unanesthetized sheep. Prostaglandins, 23, 459—468... 

Fig. 2. Pathways of 5-hydroxyeicosatetraenoic acid (HETE) and leukotriene (LT) generation. HPETE, hydroper-oxyoctadecadienoic acid LOX, lipoxygenase.

Koshihara, Y., Mizumura, M., and Murota, S. (1982) Predominant Synthesis of 5-Hydroxyeicosatetraenoic Acid by Cloned Mastocytoma P-815 Line, 2-E-6 Cells, Biochim. Biophys. Acta 772,42-47. 

LTC is still unclear). 5-Hydroxyeicosatetraenoic acid (5-HETE) is a further metabolite of 5-HPETE. 

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