Major urinary metabolites of 6-keto-prostaglandin F2α in mice

  • Posted on: 5 November 2014
  • By: fcoldren
TitleMajor urinary metabolites of 6-keto-prostaglandin F2α in mice
Publication TypeJournal Article
Year of Publication2013
AuthorsKuklev DV, Hankin JA, Uhlson CL, Hong YH, Murphy RC, Smith WL
JournalJ Lipid Res
Date Published2013 Jul
KeywordsAnimals, Chromatography, Liquid, Deuterium, Dinoprost, Humans, Isotope Labeling, Male, Mice, Mice, Inbred C57BL, Molecular Structure, Tandem Mass Spectrometry, Tritium

Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF2α urinary metabolites included dinor-6-keto-PGF2α (~10%) and dinor-13,14-dihydro-6,15-diketo-PGF1α (~10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI3 by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases.

Alternate JournalJ. Lipid Res.
PubMed ID23644380
PubMed Central IDPMC3679392
Grant ListAT-002782 / AT / NCCAM NIH HHS / United States
CA-130810 / CA / NCI NIH HHS / United States
GM-68848 / GM / NIGMS NIH HHS / United States
HL-117798 / HL / NHLBI NIH HHS / United States
P50 CA130810 / CA / NCI NIH HHS / United States
R01 GM068848 / GM / NIGMS NIH HHS / United States