Hematin-Assisted Intramolecular Oxygen Transfer Mechanism Is Involved in the Formation of 8-Hydroxy-11,12-epoxyeicosa-5,9,14-trienoic Acid (8H-11, 12-EPETE) from 12-HPETE

  • C. R. Pace-Asciak
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


We recently described the isolation and structure of two hydroxyepoxides formed from 12-HPETE by an enzyme system present in rat lung (Pace-Asciak et al.,1983a). These were shown to be 8-hydroxy-ll,12-epoxy (8H-11,12-EPETE) and 10-hydroxy-ll,12-epoxy (1 OH-11,12-EPETE) eicosatrienoic acid. Evidence was presented to show that both oxygen atoms in the hydroxyepoxides were derived from molecular oxygen (Pace-Asciak et al., 1983a). Also, when [18O]oxygenated 12-HPETE was incubated with this enzyme preparation, 18O atoms were found in both the hydroxyl and the epoxide groups, suggesting that the hydroxyl group at carbon 8 and carbon 10 was derived from the hydroperoxide of 12-HPETE (Pace-Asciak et al., 1983a). However, whether the terminal hydroxyl group of the hydroperoxide of 12-HPETE was transferred via an inter- or intramolecular mechanism was not determined. The present chapter reports evidence with a mixture of [16O]- and [18O]-labeled 12-HPETE to show a unique intramolecular rearrangement of 12-HPETE into the hydroxyepoxides catalyzed by bovine hematin in a protein-free environment as well as by a rat lung cytosol fraction.


Electron Paramagnetic Resonance Octadecadienoic Acid Ammonium Sulfate Fraction Eicosatrienoic Acid Epoxy Alcohol 
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  1. Dix, T.A., and Marnett, L.J., 1983, Hematin-catalyzed rearrangement of hydroperoxylinoleic acid to epoxy alcohols via an oxygen rebound, J. Am. Chem. Soc. 105:7001–7002.CrossRefGoogle Scholar
  2. Garssen, G.J., Veldink, G.A., Vliegenthart, J.F.G., and Boldingh, J., 1976, The formation of threo-ll-hydroxy-trans-12:13-epoxy-9-cis-octadecenoic acid by enzymic isomerisation of 13-L-hydro-peroxy-9-cis-ll-trans-octadecadienoic acid by soybean lipoxygenase-1, Eur. J. Biochem. 62:33–36.PubMedCrossRefGoogle Scholar
  3. Hamberg, M., 1975, Decomposition of unsaturated fatty acid hydroperoxides by hemoglobin: Structures of major products of 13L-hydroperoxy-9,ll-octadecadienoic acid, Lipids 10:87–92.PubMedCrossRefGoogle Scholar
  4. Hill, H. A. O., Salder, P. J., and Williams, R. J. P., 1973, The effect of 1,3,5-trinitrobenzene on 1H nuclear magnetic resonance and electron paramagnetic resonance spectra of some cobalt (II) por-phyrins, J. Chem. Soc. Dalton Trans. 1663-1667.Google Scholar
  5. Konishi, S., Hoshino, M., and Imamura, M., 1980, Formation of the charge-transfer and constrained complexes of cobalt (II) tetraphenylporphyrin in rigid solution, J. Phys. Chem. 84:3437–3440.CrossRefGoogle Scholar
  6. Pace-Asciak, C.R., 1984a, Arachidonic acid epoxides: Demonstration through 18oxygen studies of an intramolecular transfer of the terminal hydroxyl group of 12(S)-hydroperoxyeicosa-5,8,10,14-tetraenoic acid to form hydroxy epoxides, J. Biol. Chem. 259:8332–8337.PubMedGoogle Scholar
  7. Pace-Asciak, C.R., 1984b, Hemoglobin-and hemin-catalyzed transformation of 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid, Biochim. Biophys. Ada 793:485–488.CrossRefGoogle Scholar
  8. Pace-Asciak, C. R., and Martin, J., 1984a, 8-Hydroxy-ll,12-epoxyeicosatrienoic acid (8H-11,12-EPETE) enhances insulin secretion by isolated perfused pancreatic islets, in: Proceedings of the IVth International Washington Spring Symposium on Prostaglandins and Leukotrienes, Academic Press, Orlando, FL, Abstr. 88.Google Scholar
  9. Pace-Asciak, C.R., and Martin, J., 1984b, Hepoxilin, a new family of insulin secretagogues formed by intact rat pancreatic islets, J. Prostagl. Leuk. Med. 16:173–180.CrossRefGoogle Scholar
  10. Pace-Asciak, C.R., Mizuno, K., and Yamamoto, S., 1982, The enzymatic conversion of arachidonic acid into 8,11,12-trihydroxyeicosatrienoic acid: Resolution of rat lung enzyme into two active fractions, Biochim. Biophys. Acta 712:142–145.PubMedCrossRefGoogle Scholar
  11. Pace-Asciak, C.R., Granström, E., and Samuelsson, B., 1983a, Arachidonic acid epoxides: Isolation and structure of two hydroxy epoxide intermediates in the formation of 8,11,12-and 10,11,12-trihydroxyeicosatrienoic acids, J. Biol. Chem. 258:6835–6840.PubMedGoogle Scholar
  12. Pace-Asciak, C.R., Mizuno, K., and Yamamoto, S., 1983b, Resolution by DEAE-cellulose chro-matography of the enzymatic steps in the transformation of arachidonic acid into 8,11,12-and 10,11,12-trihydroxyeicosatrienoic acid by the rat lung, Prostaglandins 25:79–84.PubMedCrossRefGoogle Scholar
  13. Sok, D. E., Chung, T., and Sih, C. J., 1983, Mechanisms of leukotriene formation: Hemoglobin-catalyzed transformation of 15-HPETE into 8,15-diHETE and 14,15-diHETE isomers, Biochem.Biophys. Res. Commun. 110:273–279.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • C. R. Pace-Asciak
    • 1
    • 2
  1. 1.The Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of PharmacologyUniversity of TorontoTorontoCanada

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