5,8,11,14-Eicosatetraenoic acid, inhibition

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... 

Flynn, D.L., and Rafferty, M.F. (1986) Inhibition of 5-Hy-droxy-eicosatetraenoic acid (5-HETE) Formation in Intact Human Neutrophils by Naturally Occurring DiaryUiep-tanoids Inhibitory Activities of Curcuminoids and Yakuchi-nones. Prostaglandins Leukot. Med. 22,357-360. 

Temowitz, T., Fogh, K., and Kragballe, K. (1988) Specific Inhibition of Leukotriene B -Induced Neutrophil Chemotaxis by 15-Hydroxy-eicosatetraenoic Acid (15-HETE), Skin Pharmacol. 1, 93-99. 

Nugteren, D.H. (1970) Inhibition of Prostaglandin Bios5mthe-sis by %cis, lltrans, 14cw-Eicosatrienoic Acid and Scis, 8cis, lltrans, 14cw-Eicosatetraenoic Acid, Biochim. Biophys. Acta 210,171-176. 

The biosynthesis required NADPH and was inhibited by carbon monoxide. Experiments using strongly indicated that the 1,2-diols were formed by hydrolysis of the w6- and arachidonic acid, respectively [396], and these epoxides could later be isolated [397]. Other identified metabolites were formed by wl- and 2-oxidation [395]. Formation of several monohydroxy-eicosatetraenoic acids has also been reported [398]. 

The mechanisms of enzyme secretion and chemotaxis have obvious similarities. Thus, many chemotactic factors are also secretagogues for lysosomal enzyme secretion, e.g. fMLP [283,284]. Compounds causing secretion [285] and/or phagocytosis [286] increase the liberation of arachidonic acid from the phospholipids in a Ca -dependent manner [287]. Arachidonic acid in the presence of cytochalasin B causes enzyme release from rabbit peritoneal PMNL but not from human PMNL [152,288,290]. The acetylenic analog of arachidonic acid (5,8,11,14-eicosatetraenoic acid, ETYA) and nordihydroguiaiaretic acid (NDGA), both inhibitors of lipoxygenase, inhibit enzyme secretion induced by arachidonic acid [291,292] or chemotactic peptides and the complement factor C5a [289],... 

A unique lipoxygenase was isolated and purified from rabbit reticulocytes [212], The purified enzyme with a molecular weight of 78000 contains two moles of iron per enzyme molecule. The enzyme is identical with the previously known protein factors which inhibit the respiratory chain. The purified lipoxygenase causes a loss of acid-labile sulfur from mitochondrial electron transfer particles and acts preferably on the mitochondrial membrane. The enzyme is considered to work in the lysis of mitochondria during the maturation of erythrocytes. The major product from arachidonic acid is 15S-hydroperoxy-5,8,l 1,13-eicosatetraenoic acid, although the 12S-hydroperoxy derivative is produced as a minor product [213]. 

Siegel MI, McConnel RT, Cuatrecasas P (1979) Aspirin-like drugs interfere with arachidon-ate metabolism by inhibition of the 12-hydroxy-5,8,10,14-eicosatetraenoic acid peroxidase activity of the lipoxygenase pathway. Proc Natl Acad Sci USA 76 3774-3778 Slapke J, lager L (1979) Untersuchungen zum Analgetika-Asthma. Gesellschaft Inn Med DDR 34 78-80... 

Rabbit alveolar macrophages exhibited an apparent discrepancy between the abundance of immu-nospecific cP450 4A protein and no 20-hydroxy-eicosatetraenoic acid production (Zhu et al. 1998). NO generated by alveolar macrophages may auto-inhibit the P450 4A enzymes and production of 20-HETE in these cells. 

PGI, a metabolite of arachidonic acid (eicosatetraenoic acid) formed by enzymic oxidation and cyclisation. Prostacyclin acts as a muscle relaxant and inhibits blood platelet aggregation. See also prostaglandins, leukotrienes, eicosanoid cascade. 

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