Synthesis of Lipoxins (LX)

Stable Identifier
Homo sapiens
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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, Stsiapanava et al. 2017).
Literature References
PubMed ID Title Journal Year
16968948 The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo

Drazen, JM, Serhan, CN, Chiang, N, Yokomizo, T, Dahlén, SE, Rovati, GE, Hay, DW, Shimizu, T, Brink, C

Pharmacol Rev 2006
  Biochemistry of Lipids, Lipoproteins and Membranes, 5th Edition

Vance, JE, Vance, DE

28827365 Capturing LTAhydrolase in action: Insights to the chemistry and dynamics of chemotactic LTBsynthesis

Haeggström, JZ, Stsiapanava, A, Samuelsson, B

Proc. Natl. Acad. Sci. U.S.A. 2017
19244215 Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology

Dumlao, DS, Buczynski, MW, Dennis, EA

J Lipid Res 2009
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