Formation of cyclic products from the diepoxide of long-chain fatty esters by cytosolic epoxide hydrolase

Premjit P. Halarnkar, Jaffar Nourooz-Zadeh, Eichii Kuwano, A. Daniel Jones, Bruce D. Hammock

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Since diepoxides are known metabolites of polyunsaturated fatty acids, the action of the cytosolic epoxide hydrolase purified from liver tissue was examined on these diepoxides. Diepoxymethylstearate was metabolized to the corresponding tetraol by high concentrations of affinity-purified cytosolic epoxide hydrolase. When the enzyme was diluted (1000- to 2000-fold), disappearance of the tetraol metabolite occurred simultaneously with formation of other hydration products with GC retention times and chromatographic mobilities different from those of the tetraol. The hydration products were identified as tetrahydrofuran diols based on comparison of chromatographic properties and mass spectral information with the properties and spectra of chemically generated products. Also, a mixture of diepoxymethylarachidonates was hydrated to tetraols using concentrated enzyme. As the enzyme was diluted (1000- to 2000-fold), a decrease in tetraol formation occurred along with the elevation of other hydration products whose mass spectra were consistent with tetrahydrofuran diol structures. These data are consistent with the epoxide hydrolase at low concentrations acting to open one epoxide followed by nonenzymatic cyclization to the tetrahydrofuran diols. The data also suggest that oxygenated lipids may be endogenous substrates for the cytosolic epoxide hydrolase. Since some oxylipins are known chemical mediators, the in vivo presence and role of these novel diols and tetrahydrofuran diols should be examined.

Original languageEnglish (US)
Pages (from-to)586-593
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume294
Issue number2
DOIs
StatePublished - May 1 1992

Fingerprint

Epoxide Hydrolases
Esters
Hydration
Metabolites
Enzymes
Oxylipins
Cyclization
Epoxy Compounds
Unsaturated Fatty Acids
Liver
Tissue
Lipids
tetrahydrofuran
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Formation of cyclic products from the diepoxide of long-chain fatty esters by cytosolic epoxide hydrolase. / Halarnkar, Premjit P.; Nourooz-Zadeh, Jaffar; Kuwano, Eichii; Jones, A. Daniel; Hammock, Bruce D.

In: Archives of Biochemistry and Biophysics, Vol. 294, No. 2, 01.05.1992, p. 586-593.

Research output: Contribution to journalArticle

Halarnkar, Premjit P. ; Nourooz-Zadeh, Jaffar ; Kuwano, Eichii ; Jones, A. Daniel ; Hammock, Bruce D. / Formation of cyclic products from the diepoxide of long-chain fatty esters by cytosolic epoxide hydrolase. In: Archives of Biochemistry and Biophysics. 1992 ; Vol. 294, No. 2. pp. 586-593.
@article{2dc70c041e5a408eb332505788f0922e,
title = "Formation of cyclic products from the diepoxide of long-chain fatty esters by cytosolic epoxide hydrolase",
abstract = "Since diepoxides are known metabolites of polyunsaturated fatty acids, the action of the cytosolic epoxide hydrolase purified from liver tissue was examined on these diepoxides. Diepoxymethylstearate was metabolized to the corresponding tetraol by high concentrations of affinity-purified cytosolic epoxide hydrolase. When the enzyme was diluted (1000- to 2000-fold), disappearance of the tetraol metabolite occurred simultaneously with formation of other hydration products with GC retention times and chromatographic mobilities different from those of the tetraol. The hydration products were identified as tetrahydrofuran diols based on comparison of chromatographic properties and mass spectral information with the properties and spectra of chemically generated products. Also, a mixture of diepoxymethylarachidonates was hydrated to tetraols using concentrated enzyme. As the enzyme was diluted (1000- to 2000-fold), a decrease in tetraol formation occurred along with the elevation of other hydration products whose mass spectra were consistent with tetrahydrofuran diol structures. These data are consistent with the epoxide hydrolase at low concentrations acting to open one epoxide followed by nonenzymatic cyclization to the tetrahydrofuran diols. The data also suggest that oxygenated lipids may be endogenous substrates for the cytosolic epoxide hydrolase. Since some oxylipins are known chemical mediators, the in vivo presence and role of these novel diols and tetrahydrofuran diols should be examined.",
author = "Halarnkar, {Premjit P.} and Jaffar Nourooz-Zadeh and Eichii Kuwano and Jones, {A. Daniel} and Hammock, {Bruce D.}",
year = "1992",
month = "5",
day = "1",
doi = "10.1016/0003-9861(92)90729-G",
language = "English (US)",
volume = "294",
pages = "586--593",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Formation of cyclic products from the diepoxide of long-chain fatty esters by cytosolic epoxide hydrolase

AU - Halarnkar, Premjit P.

AU - Nourooz-Zadeh, Jaffar

AU - Kuwano, Eichii

AU - Jones, A. Daniel

AU - Hammock, Bruce D.

PY - 1992/5/1

Y1 - 1992/5/1

N2 - Since diepoxides are known metabolites of polyunsaturated fatty acids, the action of the cytosolic epoxide hydrolase purified from liver tissue was examined on these diepoxides. Diepoxymethylstearate was metabolized to the corresponding tetraol by high concentrations of affinity-purified cytosolic epoxide hydrolase. When the enzyme was diluted (1000- to 2000-fold), disappearance of the tetraol metabolite occurred simultaneously with formation of other hydration products with GC retention times and chromatographic mobilities different from those of the tetraol. The hydration products were identified as tetrahydrofuran diols based on comparison of chromatographic properties and mass spectral information with the properties and spectra of chemically generated products. Also, a mixture of diepoxymethylarachidonates was hydrated to tetraols using concentrated enzyme. As the enzyme was diluted (1000- to 2000-fold), a decrease in tetraol formation occurred along with the elevation of other hydration products whose mass spectra were consistent with tetrahydrofuran diol structures. These data are consistent with the epoxide hydrolase at low concentrations acting to open one epoxide followed by nonenzymatic cyclization to the tetrahydrofuran diols. The data also suggest that oxygenated lipids may be endogenous substrates for the cytosolic epoxide hydrolase. Since some oxylipins are known chemical mediators, the in vivo presence and role of these novel diols and tetrahydrofuran diols should be examined.

AB - Since diepoxides are known metabolites of polyunsaturated fatty acids, the action of the cytosolic epoxide hydrolase purified from liver tissue was examined on these diepoxides. Diepoxymethylstearate was metabolized to the corresponding tetraol by high concentrations of affinity-purified cytosolic epoxide hydrolase. When the enzyme was diluted (1000- to 2000-fold), disappearance of the tetraol metabolite occurred simultaneously with formation of other hydration products with GC retention times and chromatographic mobilities different from those of the tetraol. The hydration products were identified as tetrahydrofuran diols based on comparison of chromatographic properties and mass spectral information with the properties and spectra of chemically generated products. Also, a mixture of diepoxymethylarachidonates was hydrated to tetraols using concentrated enzyme. As the enzyme was diluted (1000- to 2000-fold), a decrease in tetraol formation occurred along with the elevation of other hydration products whose mass spectra were consistent with tetrahydrofuran diol structures. These data are consistent with the epoxide hydrolase at low concentrations acting to open one epoxide followed by nonenzymatic cyclization to the tetrahydrofuran diols. The data also suggest that oxygenated lipids may be endogenous substrates for the cytosolic epoxide hydrolase. Since some oxylipins are known chemical mediators, the in vivo presence and role of these novel diols and tetrahydrofuran diols should be examined.

UR - http://www.scopus.com/inward/record.url?scp=0026697278&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026697278&partnerID=8YFLogxK

U2 - 10.1016/0003-9861(92)90729-G

DO - 10.1016/0003-9861(92)90729-G

M3 - Article

C2 - 1567214

AN - SCOPUS:0026697278

VL - 294

SP - 586

EP - 593

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -