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

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 d...

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Bibliographic Details
Published inProstaglandins Vol. 33; no. 4; pp. 603 - 614
Main Authors Laposata, Michael, Kaiser, Susan L., Reich, Elizabeth L., Majerus, Philip W.
Format Journal Article
LanguageEnglish
Published Stoneham, MA Elsevier Inc 01.04.1987
Butterworth-Heinemann
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Summary: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 HSDM 1C 1 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.
ISSN:0090-6980
DOI:10.1016/0090-6980(87)90284-X