PathwayStep1948 PathwayStep1949 PathwayStep1951 PathwayStep1950 PathwayStep1952 15S-HpETE is oxidised to LXA4/B4 by ALOX5 LTA4 is converted to LXA4/B4 by ALOX12 LXA4 is oxidised to 15k-LXA4 by HPGD 15R-HETE is converted to 15epi-LXA4/B4 by ALOX5 15k-LXA4 is reduced to dhk-LXA4 by PTGR1 Synthesis of Lipoxins (LX) Authored: Williams, MG, 2012-02-24 Edited: Williams, MG, 2012-02-24 GENE ONTOLOGYGO:2001300 ISBN978-0-444-53219-0 Lipoxins A4 (LXA4) and B4 (LXB4), structurally characterized from human neutrophils incubated with 15-hydroperoxy-eicosatetraenoic acid (15-HpETE), each contain three hydroxyl moieties and a conjugated tetraene. The third hydroxyl of LXA4 is positioned at C-6, and of LXB4 at C-14. The action of arachidonate 5-lipoxygenase (ALOX5), in concert with an arachidonate 12-lipoxygenase (ALOX12) or arachidonate 15-lipoxygenase (ALOX15) activity, has been shown to produce lipoxins by three distinct pathways. Neutrophil ALOX5 can produce and secrete leukotriene A4 (LTA4) that is taken up by platelets, where it is acted upon by ALOX12 to form lipoxins. Likewise, ALOX15s can generate either 15-hydroperoxy-eicosatetraenoic acid (15-HpETE) or 15-hydro-eicosatetraenoic acid (15-HETE) that can be taken up by monocytes and neutrophils, where highly expressed ALOX5 uses it to generate lipoxins. Finally, aspirin acetylated prostaglandin G/H synthase 2 (PTGS2), rendered unable to synthesize prostaglandins, can act as a 15-lipoxygenase. This leads to the formation of 15R-HETE and culminates in creation of epi-lipoxins, which have altered stereochemistry at the C-15 hydroxyl but similar biological potency (Chiang et al. 2006, Buczynski et al. 2009, Vance & Vance 2008). Pubmed16968948 Pubmed19244215 Reactome Database ID Release 432142700 Reactome, http://www.reactome.org ReactomeREACT_150320 Reviewed: Rush, MG, 2012-11-10