13-hydroxy-9-11-octadecadienoic-acid and 5-15-dihydroxy-6-8-11-13-eicosatetraenoic-acid

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.

Topics: Arachidonate 15-Lipoxygenase; Arachidonic Acid; Arachidonic Acids; Chromatography, High Pressure Liquid; Enzyme Activation; Esterification; Humans; Hydroxyeicosatetraenoic Acids; Keratinocytes; Kinetics; Linoleic Acids