Mechanisms of leukotriene formation: hemoglobin-catalyzed transformation of 15-HPETE into 8,15-DiHETE and 14,15-DiHETE isomers.
Four isomers of 8,15-diHETE as well as 14,15-diHETEs are isolated and characterized after exposure of 15-HPETE to hemoglobin. It is found that 83% of the C-8 oxygen atoms in 8(R), 15(S)-diHETE and 8(S), 15(S)-diHETE, and 41% of the C-8 oxygen atoms in 8(R), 15(S)-11Z-diHETE and 8(S), 15(S)-11Z-diHETE are derived from H2(18)O. These results suggest that hemoglobin catalyzes the transformation of 15-HPETE into these products via a free radical process, possibly involving the intermediacy of 14,15-LTA. Intact human leukocytes contain a distinct enzyme system for catalyzing the conversion of 15-HPETE into 14,15-LTA. This enzyme activity is inhibited by ETYA and is rapidly denatured upon homogenization of the intact leukocytes.
D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis* / Q000378:metabolism*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D006454:Hemoglobins / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism*; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D006454:Hemoglobins; D015289:Leukotrienes; D008054:Lipid Peroxides; D007975:Leukotriene B4; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid