(5S,6Z,8E,10E,14Z)-5-hydroxy-12-oxoicosa-6,8,10,14-tetraenoic acid

Description

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. 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. 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. 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.

Uses

12-oxo Leukotriene B4 in acetonitrile is a potent eicosanoid lipid mediators.

Definition

ChEBI: A long-chain fatty acid consisting of leukotriene B4 having a 12-keto group in place of the 12-hydroxy group.

References

[1] T. YOKOMIZO. Enzymatic inactivation of leukotriene B4 by a novel enzyme found in the porcine kidney. Purification and properties of leukotriene B4 12-hydroxydehydrogenase.[J]. The Journal of Biological Chemistry, 1993, 292 1: 18128-18135. DOI: 10.1016/s0021-9258(17)46820-7
[2] S. WAINWRIGHT W P. 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]. The Journal of Biological Chemistry, 1991, 43 1: 20899-20906. DOI: 10.1016/s0021-9258(18)54795-5
[3] P WHEELAN. Metabolism of leukotriene B4 by cultured human keratinocytes. Formation of glutathione conjugates and dihydro metabolites.[J]. The Journal of Biological Chemistry, 1993, 268 34: 25439-25448.
[4] W S POWELL. Effects of metabolites of leukotriene B4 on human neutrophil migration and cytosolic calcium levels.[J]. Journal of Pharmacology and Experimental Therapeutics, 1996, 276 2: 728-736.