Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts
| Autor: | Arthur A. Spector, Xiang Fang, Mike VanRollins, Terry L. Kaduce, Neal L. Weintraub |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Stereochemistry
Metabolite Cell peroxisomes Human skin QD415-436 Cell Biology Peroxisome Biochemistry eicosanoids Acyl-CoA chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Eicosanoid cytochrome P450 epoxygenase arachidonic acid cardiovascular system medicine β-oxidation lipids (amino acids peptides and proteins) Arachidonic acid |
| Zdroj: | Journal of Lipid Research, Vol 41, Iss 1, Pp 66-74 (2000) |
| ISSN: | 0022-2275 |
| DOI: | 10.1016/s0022-2275(20)32075-7 |
| Popis: | Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cyto- chrome 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- 3 H)11,12-EET (( 3 H)11,12-EET) and (1- 14 C)11,12-EET demonstrated that chain-shortened metabo- lites 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-epoxyocta- decadienoic acid (9,10-epoxy-18:2) and 5,6-epoxytetrade- caenoic 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). ( 3 H)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 iden- tify 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 Zell- weger syndrome and acyl CoA oxidase-deficient fibro- blasts. We conclude that the chain-shortened epoxy-fatty acids are produced primarily by peroxisomal b -oxidation. This may serve as an alternate mechanism for EET inactiva- tion 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 b -oxidation pathway is to generate these products. —Fang, X., T. L. Ka- duce, M. VanRollins, N. L. Weintraub, and A. A. Spector. Conversion of epoxyeicosatrienoic acids (EETS) to chain- shorted epoxy fatty acids by human skin fibroblasts. J. Lipid Res. 2000. 41: 66-74. |
| Databáze: | OpenAIRE |
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