Arachidonic acid metabolism in isolated pancreatic islets. V. The enantiomeric composition of 12-hydroxy-5,8,10,14-eicosatetraenoic acid indicates synthesis by a 12-lipoxygenase rather than a monooxygenase

John Turk, Bryan A. Wolf, Richard A. Easom, Jonathan H. Hughes, Michael L. McDaniel

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Recent evidence indicates that the arachidonate metabolite 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) or its precursor may act as a second messenger in stimulus-response coupling in a variety of cells including Aplysia neurons, adrenal glomerulosa cells, and pancreatic islets. The compound 12(S)-HETE is generated from the precursor 12(S)-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12(S)-HPETE), which is a product of the 12-lipoxygenase enzyme. Some cells have recently been found to produce the enantiomer 12(R)-HETE, apparently via a cytochrome P-450 monooxygenase, and the biologic actions of 12(R)-HETE and 12(S)-HETE differ. We have examined the stereochemistry of 12-HETE from isolated pancreatic islets both radiochemically and by a new mass spectrometric method capable of quantitating subnanogram amounts of 12-HETE stereoisomers. Endogenous 12-HETE from islets was found to be exclusively the S-isomer. d-Glucose stimulated both insulin secretion and islet accumulation of 12(S)-HETE but not of 12(R)-HETE. Pharmacologic inhibition of islet 12-HETE biosynthesis also suppressed glucose-induced insulin secretion. These findings suggest that islet 12-HETE is a product of a 12-;ipoxygenase rather than of a cytochrome P-450 monooxygenase and further implicate 12-lipoxygenase products in stimulus-secretion coupling.

Original languageEnglish
Pages (from-to)16-24
Number of pages9
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume1001
Issue number1
DOIs
StatePublished - Jan 23 1989

Keywords

  • 12-Lipoxygenase
  • Enantiomer
  • Hydroxyicosatetraenoic acid
  • Stimulus-response coupling

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