Evidence for a novel pathway of leukotriene formation in human platelets.
The metabolism of arachidonic acid via lipoxygenase-catalyzed reactions in washed human platelets was investigated. In addition to the previously discovered lipoxygenase metabolites, 12-hydroxyeicosatetraenoic acid, 15-hydroxyeicosatetraenoic acid, 8,15-dihydroxyeicosatetraenoic acid and 14,15-dihydroxyeicosatetraenoic acid, several other products were formed. The compounds were all dihydroxylated metabolites of arachidonic acid, containing a conjugated triene structure, and identified as 11,12-dihydroxyeicosatetraenoic acid (two isomers) and 5,12-dihydroxyeicosatetraenoic acid (four isomers). The identification was based on ultraviolet spectroscopy and gas chromatography-mass spectrometry of native and hydrogenated compounds. Stereochemical analysis of the hydroxyl groups of the 5,12-dihydroxyeicosatetraenoic acids and experiments with 18O2 indicated that the compounds were formed by the 12-lipoxygenase pathway, probably via an unstable epoxide.
Westlund
P
P
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Edenius
C
C
Lindgren
J A
JA
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis* / Q000097:blood / Q000302:isolation & purification; D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis* / Q000097:blood / Q000302:isolation & purification; D007975:Leukotriene B4 / Q000097:blood; D015289:Leukotrienes; D008084:Lipoxygenase / Q000097:blood; D008968:Molecular Conformation; D010103:Oxygen Isotopes; D013237:Stereoisomerism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D010103:Oxygen Isotopes; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C021201:12-HPETE; D008084:Lipoxygenase