Reactome | Biosynthesis of Lipoxins (LX)

Biosynthesis of Lipoxins (LX)

Stable Identifier

R-HSA-2142700

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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 Chiang, N, Serhan, CN, Dahlén, SE, Drazen, JM, Hay, DW, Rovati, GE, Shimizu, T, Yokomizo, T, Brink, C	Pharmacol Rev	2006
	Biochemistry of Lipids, Lipoproteins and Membranes, 5th Edition Vance, DE, Vance, JE		2008
28827365	Capturing LTAhydrolase in action: Insights to the chemistry and dynamics of chemotactic LTBsynthesis Stsiapanava, A, Samuelsson, B, Haeggström, JZ	Proc. Natl. Acad. Sci. U.S.A.	2017
19244215	Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology Buczynski, MW, Dumlao, DS, Dennis, EA	J Lipid Res	2009