Transformations of 5-HETE by activated keratinocyte 15-lipoxygenase and the activation mechanism.
There is convincing evidence that normal cultured human keratinocytes possess a 15-lipoxygenase activity which, however, does not appear to manifest itself without cell membrane damage. When "activated", this enzyme transforms arachidonic acid into 15-hydroxyeicosatetraenoic acid (15-HETE), and linoleic acid into 13-hydroxyoctadecadienoic acid, presumably by peroxidase action on their respective hydroperoxy intermediates. Normal but not membrane-damaged keratinocytes metabolize exogenous 5-HETE, principally by esterifying the eicosanoid intact, primarily in the triacylglycerol fraction. In the present study, membrane-damaged keratinocytes were found to transform 5-HETE to 5,15-diHETE and also to a lipoxin-like group of tetraenes. Similar, if not identical, tetraenes were produced by action of the keratinocyte enzyme on 5(S),15(S)-diHETE, which points to the role of the latter as an intermediate between 5-HETE and the tetraenes. A direction for further study of the mechanism of the "activation" step is presented.
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Department of Medicine, State University of New York, Buffalo.
D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D004951:Esterification; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D015603:Keratinocytes / Q000201:enzymology*; D007700:Kinetics; D008041:Linoleic Acids / Q000378:metabolism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; C034922:5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase