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 Citations (Scopus)

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 - 1987
Externally publishedYes

Fingerprint

Eicosanoids
Arachidonic Acid
Prostaglandin-Endoperoxide Synthases
Acids
Fatty Acids
8,11,14-Eicosatrienoic Acid
Cells
Coenzyme A Ligases
Tissue culture
Acyl Coenzyme A
Fibrosarcoma
Poisons
Coenzyme A
Platelets
Detergents
Optical microscopy
Culture Media
Microscopy
Cultured Cells
Brain

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Eicosadiynoic acid : A non-toxic inhibitor of multiple enzymatic steps in the production of icosanoids from arachidonic acid. / Laposata, Michael; Kaiser, Susan L.; Reich, Elizabeth L.; Majerus, Philip W.

In: Prostaglandins, Vol. 33, No. 4, 1987, p. 603-614.

Research output: Contribution to journalArticle

Laposata, Michael ; Kaiser, Susan L. ; Reich, Elizabeth L. ; Majerus, Philip W. / Eicosadiynoic acid : A non-toxic inhibitor of multiple enzymatic steps in the production of icosanoids from arachidonic acid. In: Prostaglandins. 1987 ; Vol. 33, No. 4. pp. 603-614.
@article{efb64ba31d9f4c7785c03ef12f25a0ac,
title = "Eicosadiynoic acid: A non-toxic inhibitor of multiple enzymatic steps in the production of icosanoids from arachidonic acid",
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.",
keywords = "Arachidonic Acid/Icosanoids/Fatty Acids/ Prostaglandin Inhibitors/Acyl-CoA Synthetase",
author = "Michael Laposata and Kaiser, {Susan L.} and Reich, {Elizabeth L.} and Majerus, {Philip W.}",
year = "1987",
doi = "10.1016/0090-6980(87)90284-X",
language = "English (US)",
volume = "33",
pages = "603--614",
journal = "Prostaglandins and Other Lipid Mediators",
issn = "1098-8823",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Eicosadiynoic acid

T2 - A non-toxic inhibitor of multiple enzymatic steps in the production of icosanoids from arachidonic acid

AU - Laposata, Michael

AU - Kaiser, Susan L.

AU - Reich, Elizabeth L.

AU - Majerus, Philip W.

PY - 1987

Y1 - 1987

N2 - 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.

AB - 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.

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

UR - http://www.scopus.com/inward/record.url?scp=0023275834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023275834&partnerID=8YFLogxK

U2 - 10.1016/0090-6980(87)90284-X

DO - 10.1016/0090-6980(87)90284-X

M3 - Article

VL - 33

SP - 603

EP - 614

JO - Prostaglandins and Other Lipid Mediators

JF - Prostaglandins and Other Lipid Mediators

SN - 1098-8823

IS - 4

ER -