Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE2and 5-Hydroxy-PGD2

Fumie Nakashima, Takashi Suzuki, Odaine N. Gordon, Dominic Golding, Toshiaki Okuno, Juan A. Giménez-Bastida, Takehiko Yokomizo, Claus Schneider

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The biosynthetic crossover of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymatic activities is a productive pathway to convert arachidonic acid into unique eicosanoids. Here, we show that COX-2 catalysis with 5-LOX derived 5-hydroxy-eicosatetraenoic acid yields the endoperoxide 5-hydroxy-PGH2 that spontaneously rearranges to 5-OH-PGE2 and 5-OH-PGD2, the 5-hydroxy analogs of arachidonic acid derived PGE2 and PGD2. The endoperoxide was identified via its predicted degradation product, 5,12-dihydroxy-heptadecatri-6E,8E,10E-enoic acid, and by SnCl2-mediated reduction to 5-OH-PGF2α. Both 5-OH-PGE2 and 5-OH-PGD2 were unstable and degraded rapidly upon treatment with weak base. This instability hampered detection in biologic samples which was overcome by in situ reduction using NaBH4 to yield the corresponding stable 5-OH-PGF2 diastereomers and enabled detection of 5-OH-PGF2α in activated primary human leukocytes. 5-OH-PGE2 and 5-OH-PGD2 were unable to activate EP and DP prostanoid receptors, suggesting their bioactivity is distinct from PGE2 and PGD2.

Original languageEnglish (US)
Pages (from-to)1380-1388
Number of pages9
JournalJournal of the American Chemical Society
Issue number9
StatePublished - Sep 27 2021
Externally publishedYes


  • arachidonic acid
  • bioactive lipid
  • catalysis
  • eicosanoid
  • endoperoxide
  • leukocyte
  • prostaglandin

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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