Document Detail

Cytochrome P450-dependent metabolism of eicosapentaenoic acid in the nematode Caenorhabditis elegans.
MedLine Citation:
PMID:  18282462     Owner:  NLM     Status:  MEDLINE    
The genome of Caenorhabditis elegans contains 75 full length cytochrome P450 (CYP) genes whose individual functions are largely unknown yet. We tested the hypothesis that some of them may be involved in the metabolism of eicosapentaenoic acid (EPA), the predominant polyunsaturated fatty acid of this nematode. Microsomes isolated from adult worms contained spectrally active CYP proteins and showed NADPH-CYP reductase (CPR) activities. They metabolized EPA and with lower activity also arachidonic acid (AA) to specific sets of regioisomeric epoxy- and omega-/(omega-1)-hydroxy-derivatives. 17(R),18(S)-epoxyeicosatetraenoic acid was produced as the main EPA metabolite with an enantiomeric purity of 72%. The epoxygenase and hydroxylase reactions were NADPH-dependent, required the functional expression of the CPR-encoding emb-8 gene, and were inhibited by 17-ODYA and PPOH, two compounds known to inactivate mammalian AA-metabolizing CYP isoforms. Multiple followed by single RNAi gene silencing experiments identified CYP-29A3 and CYP-33E2 as the major isoforms contributing to EPA metabolism in C. elegans. Liquid chromatography/mass spectrometry revealed that regioisomeric epoxy- and hydroxy-derivatives of EPA and AA are endogenous constituents of C. elegans. The endogenous EPA metabolite levels were increased by treating the worms with fenofibrate, which also induced the microsomal epoxygenase and hydroxylase activities. These results demonstrate for the first time that C. elegans shares with mammals the capacity to produce CYP-dependent eicosanoids and may thus facilitate future studies on the mechanisms of action of this important class of signaling molecules.
Jana Kulas; Cosima Schmidt; Michael Rothe; Wolf-Hagen Schunck; Ralph Menzel
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-02-08
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  472     ISSN:  1096-0384     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-04-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  65-75     Citation Subset:  IM    
Humboldt University at Berlin, Department of Biology, Freshwater and Stress Ecology, Spaethstr. 80/81, 12437 Berlin, Germany.
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MeSH Terms
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / metabolism*
Cytochrome P-450 Enzyme System / metabolism*
Eicosapentaenoic Acid / metabolism*
Tissue Distribution
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 1553-41-9/Eicosapentaenoic Acid; 9035-51-2/Cytochrome P-450 Enzyme System

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