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Leukotriene B4 (LTB4) is a dihydroxy fatty acid derived from arachidonic acid through the 5-LO pathway. It promotes a number of leukocyte functions including aggregation, stimulation of ion fluxes, enhancement of lysosomal enzyme release, superoxide anion production, chemotaxis, and chemokinesis. 12-oxo LTB4 is an initial metabolite of LTB4 formed via the LTB4 12-hydroxydehydrogenase pathway.1,2,3 It is rapidly converted to 10,11-dihydro-12-oxo-LTB4, followed by reduction of the 12-oxo group to give 10,11-dihydro-LTB4.2 12-oxo-LTB4 (EC50 = 33 nM) is about 70-fold less potent than LTB4 (EC50 = 0.46 nM) at stimulating Ca2+ mobilization in human neutrophils.4 It is also significantly less potent than LTB4 at stimulating neutrophil migration with EC50 values of 170 and 2.7 nM for 12-oxo-LTB4 and LTB4, respectively.4
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1
Yokomizo, T., Izumi, T., Takahashi, T., et al. Enzymatic inactivation of leukotriene B4 by a novel enzyme found in the porcine kidney. Purification and properties of leukotriene B4 12-hydroxydehydrogenase. J Biol Chem 268 18128-18135 (1993).
2
Wainwright, S.L., Powell, W.S. Mechanism for the formation of dihydro metabolites of 12-hydroxyeicosanoids conversion of leukotriene B4 and 12-hydroxy-5,8,10,14-eicosatetraenoic acid to 12-oxo intermediates. J Biol Chem 266(31) 20899-20906 (1991).
3
Wheelan, P., Zirrolli, J.A., Morelli, J.G., et al. Metabolism of leukotriene B4 by cultural human keratinocytes. Formation of glutathione conjugates and dihydro metabolites. J Biol Chem 268 25439-25448 (1993).
4
Powell, W.S., Rokach, J., Khanapure, S.P., et al. Effects of metabolites of leukotriene B4 on human neutrophil migration and cytosolic calcium levels. J Pharmacol Exp Ther 276(2) 728-736 (1996).
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