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 20:2 delta 8a, 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 delta 5 desaturase inhibitor. Finally, EDYA (50 microM) 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 microM, 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.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors; D004537:Eicosanoic Acids / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D003066:Coenzyme A Ligases