Biosynthesis of Lipoxins (LX)

Summary
Organism
Homo sapiens (human)
Reactome
R-HSA-2142700
PubChem
R-HSA-2142700
Description
  • 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).
Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.
Displaying all 2 entries
UniProt ID Protein Name Gene Symbol Pathway Viewer
P18054 Polyunsaturated fatty acid lipoxygenase ALOX12
  • 12LO
  • ALOX12
  • LOG12
view
P20292 Arachidonate 5-lipoxygenase-activating protein
  • ALOX5AP
  • FLAP
view

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Acknowledgements

Supported by JST NBDC Grant Number JPMJND2204

Partly supported by NIH Common Fund Grant #1U01GM125267-01


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