Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts

Xiang Fang, Terry L. Kaduce, Mike VanRollins, Neal L. Weintraub, Arthur A. Spector

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs). However, we find that human skin fibroblasts convert EETs mostly to chain-shortened epoxy-fatty acids and produce only small amounts of DHETs. Comparative studies with [5,6,8,9,11,12,14,15-3H]11,12-EET ([3H]11,12-EET) and [114C]11,12-EET demonstrated that chain-shortened metabolites are formed by removal of carbons from the carboxyl end of the EET. These metabolites accumulated primarily in the medium, but small amounts also were incorporated into the cell lipids. The most abundant 11,12-EET product was 7,8-epoxyhexadecadienoic acid (7,8-epoxy-16:2), and two of the others that were identified are 9,10-epoxyoctadecadienoic acid (9,10-epoxy-18:2) and 5,6- epoxytetradecaenoic acid (5,6-epoxy-14:1). The main epoxy-fatty acid produced from 14,15-EET was 10,11-epoxyhexadecadienoic acid (10,11-epoxy-16:2). [3H]8,9-EET was converted to a single metabolite with the chromatographic properties of a 16-carbon epoxy-fatty acid, but we were not able to identify this compound. Large amounts of the chain-shortened 11,12-EET metabolites were produced by long-chain acyl CoA dehydrogenase-deficient fibroblasts but not by Zellweger syndrome and acyl CoA oxidase-deficient fibroblasts. We conclude that the chain-shortened epoxy-fatty acids are produced primarily by peroxisomal β-oxidation. This may serve as an alternate mechanism for EET inactivation and removal from the tissues. However, it is possible that the epoxy-fatty acid products may have metabolic or functional effects and that the purpose of the β-oxidation pathway is to generate these products.

Original languageEnglish (US)
Pages (from-to)66-74
Number of pages9
JournalJournal of Lipid Research
Volume41
Issue number1
StatePublished - Jan 2000
Externally publishedYes

Fingerprint

Fibroblasts
Skin
Fatty Acids
Metabolites
Acids
Long-Chain Acyl-CoA Dehydrogenase
Carbon
Zellweger Syndrome
Acyl-CoA Oxidase
Tissue
Oxidation
Eicosanoids
Arachidonic Acid
Cytochrome P-450 Enzyme System
11,12-epoxy-5,8,14-eicosatrienoic acid
Lipids

Keywords

  • β-oxidation
  • Arachidonic acid
  • Cytochrome 1'450 epoxygenase
  • Eicosanoids
  • Peroxisomes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts. / Fang, Xiang; Kaduce, Terry L.; VanRollins, Mike; Weintraub, Neal L.; Spector, Arthur A.

In: Journal of Lipid Research, Vol. 41, No. 1, 01.2000, p. 66-74.

Research output: Contribution to journalArticle

Fang, X, Kaduce, TL, VanRollins, M, Weintraub, NL & Spector, AA 2000, 'Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts', Journal of Lipid Research, vol. 41, no. 1, pp. 66-74.
Fang, Xiang ; Kaduce, Terry L. ; VanRollins, Mike ; Weintraub, Neal L. ; Spector, Arthur A. / Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts. In: Journal of Lipid Research. 2000 ; Vol. 41, No. 1. pp. 66-74.
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abstract = "Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs). However, we find that human skin fibroblasts convert EETs mostly to chain-shortened epoxy-fatty acids and produce only small amounts of DHETs. Comparative studies with [5,6,8,9,11,12,14,15-3H]11,12-EET ([3H]11,12-EET) and [114C]11,12-EET demonstrated that chain-shortened metabolites are formed by removal of carbons from the carboxyl end of the EET. These metabolites accumulated primarily in the medium, but small amounts also were incorporated into the cell lipids. The most abundant 11,12-EET product was 7,8-epoxyhexadecadienoic acid (7,8-epoxy-16:2), and two of the others that were identified are 9,10-epoxyoctadecadienoic acid (9,10-epoxy-18:2) and 5,6- epoxytetradecaenoic acid (5,6-epoxy-14:1). The main epoxy-fatty acid produced from 14,15-EET was 10,11-epoxyhexadecadienoic acid (10,11-epoxy-16:2). [3H]8,9-EET was converted to a single metabolite with the chromatographic properties of a 16-carbon epoxy-fatty acid, but we were not able to identify this compound. Large amounts of the chain-shortened 11,12-EET metabolites were produced by long-chain acyl CoA dehydrogenase-deficient fibroblasts but not by Zellweger syndrome and acyl CoA oxidase-deficient fibroblasts. We conclude that the chain-shortened epoxy-fatty acids are produced primarily by peroxisomal β-oxidation. This may serve as an alternate mechanism for EET inactivation and removal from the tissues. However, it is possible that the epoxy-fatty acid products may have metabolic or functional effects and that the purpose of the β-oxidation pathway is to generate these products.",
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AU - Spector, Arthur A.

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N2 - Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs). However, we find that human skin fibroblasts convert EETs mostly to chain-shortened epoxy-fatty acids and produce only small amounts of DHETs. Comparative studies with [5,6,8,9,11,12,14,15-3H]11,12-EET ([3H]11,12-EET) and [114C]11,12-EET demonstrated that chain-shortened metabolites are formed by removal of carbons from the carboxyl end of the EET. These metabolites accumulated primarily in the medium, but small amounts also were incorporated into the cell lipids. The most abundant 11,12-EET product was 7,8-epoxyhexadecadienoic acid (7,8-epoxy-16:2), and two of the others that were identified are 9,10-epoxyoctadecadienoic acid (9,10-epoxy-18:2) and 5,6- epoxytetradecaenoic acid (5,6-epoxy-14:1). The main epoxy-fatty acid produced from 14,15-EET was 10,11-epoxyhexadecadienoic acid (10,11-epoxy-16:2). [3H]8,9-EET was converted to a single metabolite with the chromatographic properties of a 16-carbon epoxy-fatty acid, but we were not able to identify this compound. Large amounts of the chain-shortened 11,12-EET metabolites were produced by long-chain acyl CoA dehydrogenase-deficient fibroblasts but not by Zellweger syndrome and acyl CoA oxidase-deficient fibroblasts. We conclude that the chain-shortened epoxy-fatty acids are produced primarily by peroxisomal β-oxidation. This may serve as an alternate mechanism for EET inactivation and removal from the tissues. However, it is possible that the epoxy-fatty acid products may have metabolic or functional effects and that the purpose of the β-oxidation pathway is to generate these products.

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