title: Major urinary metabolites of 6-keto-prostaglandin F2α in mice.
abstract: 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.
authors: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Dmitry V
authors: DV
authors: Kuklev
authors: Joseph A
authors: JA
authors: Hankin
authors: Charis L
authors: CL
authors: Uhlson
authors: Yu H
authors: YH
authors: Hong
authors: Robert C
authors: RC
authors: Murphy
authors: William L
authors: WL
authors: Smith
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D003903:Deuterium / Q000737:chemistry; D015237:Dinoprost / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D053719:Tandem Mass Spectrometry; D014316:Tritium / Q000737:chemistry
chemical_list: C078129:6-keto-prostaglandin F2alpha; D014316:Tritium; D003903:Deuterium; D015237:Dinoprost
keywords: cyclooxygenase; eicosapentaenoic acid; fish oil; prostacyclin
references: Curr Atheroscler Rep. 2008 Dec;10(6):503-9
references: 18937898
references: Anal Biochem. 1986 May 15;155(1):198-205
references: 3087234
references: J Biol Chem. 1983 Mar 10;258(5):3285-93
references: 6338016
references: FASEB J. 2006 Jun;20(8):1097-108
references: 16770009
references: J Biol Chem. 2007 Jan 12;282(2):1498-506
references: 17110378
references: Biochim Biophys Acta. 1989 Jun 8;1003(2):161-6
references: 2659082
references: J Pharmacol Exp Ther. 2007 Aug;322(2):453-60
references: 17473175
references: Adv Exp Med Biol. 1997;400A:183-7
references: 9547556
references: Blood. 2006 May 1;107(9):3572-4
references: 16397127
references: J Biochem. 2004 Apr;135(4):455-63
references: 15115769
references: Anal Biochem. 1981 Aug;115(2):359-67
references: 7030131
references: Am J Clin Nutr. 2008 Jun;87(6):1997S-2002S
references: 18541601
references: Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):272-7
references: 9874808
references: J Biol Chem. 1964 Nov;239:PC4006-8
references: 14257636
references: Chem Rev. 2011 Oct 12;111(10):5821-65
references: 21942677
references: Circulation. 2012 Mar 6;125(9):1084-93
references: 22282329
references: J Biol Chem. 2008 Jun 6;283(23):15533-7
references: 18285331
references: Circulation. 2009 Feb 17;119(6):902-7
references: 19171857
references: Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86
references: 15591226
references: Cancer Res. 2007 Oct 1;67(19):9380-8
references: 17909047
references: Prostaglandins. 1989 Nov;38(5):509-21
references: 2557651
references: Br J Pharmacol. 1991 Jul;103(3):1663-8
references: 1933130
references: Bioorg Khim. 1993 Nov;19(11):1122-7
references: 8285925
references: J Biol Chem. 1995 Oct 13;270(41):24019-23
references: 7592599
references: Biochim Biophys Acta. 1988 Feb 4;958(2):289-99
references: 2827784
references: J Biol Chem. 2009 Apr 10;284(15):10046-55
references: 19218248
references: Biochim Biophys Acta. 1986 Oct 3;878(3):387-93
references: 3756200
references: Anal Biochem. 2004 Nov 15;334(2):266-75
references: 15494133
references: Circ Res. 2010 Feb 5;106(2):337-45
references: 19940265
references: J Biol Chem. 2007 Aug 3;282(31):22254-66
references: 17519235
references: J Clin Invest. 1981 Nov;68(5):1272-6
references: 7028786
references: J Biol Chem. 1994 Feb 25;269(8):5527-36
references: 8119886
references: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:483-93
references: 12432938
references: Biochim Biophys Acta. 1980 Aug 11;619(2):207-13
references: 6996737
references: Nature. 1984 Jan 12-18;307(5947):165-8
references: 6318123
references: J Lipid Res. 2009 Apr;50 Suppl:S219-23
references: 18957694
references: Br J Nutr. 2010 Dec;104(11):1586-600
references: 21118617
references: Mol Pharmacol. 2010 Jun;77(6):979-86
references: 20194532
references: Cancer Metastasis Rev. 2011 Dec;30(3-4):409-17
references: 22020925