Eicosadiynoic acid: A non-toxic inhibitor of multiple enzymatic steps in the production of icosanoids from arachidonic acid

Michael Laposata, Susan L. Kaiser, Elizabeth L. Reich, Philip W. Majerus

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We have studied the acetylenic fatty acid 20:2Δ8a, 11a (eicosadiynoic acid, EDYA). It was found that this compound acts as an inhibitor of several steps in the production of icosanoids from arachidonic acid. First, the compound was shown to inhibit arachidonate uptake by platelets. Second, using a detergent solubilized preparation from calf brain, EDYA was found to inhibit both the arachidonoyl and the non-specific long chain acyl-CoA synthetase, which convert arachidonate to its CoA ester. Third, the compound decreased the conversion of dihomo gamma linolenic acid to arachidonate in the mouse fibrosarcoma HSDM1C1 cell line, acting as an apparent Δ5 desaturase inhibitor. Finally, EDYA (50 uM) inhibited cyclooxygenase activity. The compound was not toxic to cultured cells. Cells were grown for months in tissue culture medium at concentrations as high as 50 uM, with no morphologic changes by light microscopy and no prolongation of the doubling time over untreated cells. Our findings with this compound indicate that it limits icosanoid production by inhibiting cyclooxygenase and also by limiting arachidonate uptake, activation, and production from precursor fatty acids.

Original languageEnglish (US)
Pages (from-to)603-614
Number of pages12
JournalProstaglandins
Volume33
Issue number4
DOIs
StatePublished - Apr 1987
Externally publishedYes

Keywords

  • Arachidonic Acid/Icosanoids/Fatty Acids/ Prostaglandin Inhibitors/Acyl-CoA Synthetase

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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