Lipoxygenase catalyzed oxygenation of hydroxy fatty acids to lipoxins.
The pure lipoxygenases from rabbit reticulocytes and soybeans convert a variety of substrates (arachidonic acid, 15-HPETE, 15-HETE, 5-HETE, various DiHETE isomers) to trihydroxy eicosanoids containing a conjugated tetraene system (lipoxins). In general, the methyl esters are better substrates for lipoxin formation than are the free acids. Lipoxygenase inhibitors (5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid) strongly inhibit the lipoxin formation. The complete stereochemistry of the lipoxin B formed from 15S-HETE methyl ester has been established by co-chromatography with authentic standards on various types of HPLC columns, by GC/MS analysis, by gas liquid chromatography of the ozonolysis fragments of the menthoxy carbonyl derivatives and 1H-NMR studies. The molar absorption coefficient of the conjugated tetraenes was measured as epsilon 301 = 53,000. The lipoxins formed from 15-HETE and various DiHETE isomers are formed exclusively via the oxygenation pathway as shown by experiments under an 17O2 atmosphere and/or by anaerobic incubations. Our results indicate that lipoxins can be synthesized via lipoxygenase-catalyzed sequential oxygenation of polyenoic fatty acids and their hydro(pero)xy derivatives.
D000818:Animals; D004952:Esters / Q000378:metabolism; D006880:Hydroxy Acids / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis* / Q000378:metabolism; D044045:Lipoxins; D008084:Lipoxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology; D013025:Glycine max / Q000201:enzymology; D013056:Spectrophotometry, Ultraviolet; D013379:Substrate Specificity
D004952:Esters; D006880:Hydroxy Acids; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C057024:15-hydroxy-5,8,11,13 eicosatetraenoic acid methyl ester; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C042651:lipoxin B4; D008084:Lipoxygenase