15-HETE

Lipoxygenation is the major pathway of dioxygenation of arachidonic acid in blood platelets and leads to the 12-5-hydroperoxy acid 12-HPETE and the corresponding 12-hydroxy acid 12-HETE. Several pathways for the synthesis of 12-HETE have been developed. However, despite the availability of this substance, its biological role remains undetermined. 

HETE was also obtained together with ( )-ll-HETE via the epoxide opening reaction of 11,12-epoxyarachidonic acid (Ref. 4). 

Scheme 19. The Sonogashira coupling in Nicolaou s synthesis of (12S)-HETE (78).

We have already stressed the potential importance of lipid-rich membranes in the skin as potential targets for ROS-induced damage and ageing of human skin is morphologically identical to changes found by peroxidative processes (Serri et al., 1977). The involvement of AA metabolites in skin disease, and in particular psoriasis, has been the subject of much recent interest. Studies have included topical and intradermal administrations of AA metabolites, and assay of such products in clinical specimens. Results show that concentration of AA, 12-hydroxy-eicosatetraenoic acid (12-HETE), PG and leu-kotrienes are increased in psoriatic lesions (Hammarstrom etal., 1975 Camp etal., 1983 Brain etal., 1984 Duell et al., 1988) and also that full-thickness epidermis from normal and diseased skin has the enzymatic capacity to convert AA to some of the same metabolites (Hammarstrom etal., 1975, 1979 Camp etal., 1983 Brain etal., 1984 Ziboh et al., 1984 DueU et al., 1988). The biological effect of both 12-HETE and leukotrienes was confirmed by both topical application and intradermal injection, which caused epidermal inflammation and... 

HETE, 12-hydroxyeicosatetraenoic acid HL60, human promyelocytic leukemia cells... 

Eicosanoid synthesis. Arachidonic acid is converted by cyclooxygenases into prostaglandins, and thromboxanes. Lipoxygenases convert arachidonic acid into HPETEs, which are then converted to lipoxins, leukotrienes, and 12-HETE (hydroxyeicosatetraenoic acid). Epoxygenases convert arachidonic acid into epoxides. 

Additional lipoxygenases are known which oxygenate different positions on the arachidonic acid chain. 12-LO, resulting in the formation of 12-HETE (7), is best known in platelets, while the 15-LO from soybean has been studied in detail for many years [8]. 15-HETE (8) is also produced by mammalian cells the enzymes from neutrophils and particularly rabbit reticulocytes are the best characterized. 

Timegadine (168) is an atypical basic NSAID which has shown efficacy in arthritis clinical trials [426,427]. It is a potent CO inhibitor in a variety of tissues, and also inhibited the production of 12-HETE from platelet ho-... 

Figure 4.35 Synthesis of 20,20,20-trifluoroarachidonic acid and its transformation into 20,20,20-trifluoroleukotriene 64 (LTB4) and trifluoro-12-HETE.

Previously, we reported the effects of Morus flavonoids on arachidonate metabolism in rat platelet homogenates, such as inhibition of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), thromboxane B2, and 12-hydroxy -5,8,10,14-eicosatetraenoic acid (12-HETE) [79,80]. As described in the... 

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