Epoxidation of C18 unsaturated fatty acids by cytochromes P4502C2 and P4502CAA

Ronald M. Laethem, Michael Balazy, Dennis Koop

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The regioselective epoxidation of oleic, linoleic, α-linolenic, and γ-linolenic acid by cytochromes P4502CAA and P4502C2 was characterized. Epoxide metabolites for all fatty acids were resolved by normal phase HPLC and identified by gas chromatography and mass spectrometry. Both isoforms epoxidized the single double bond in oleic acid and both double bonds in linoleic acid. The ratio of the two epoxides produced with linoleic add (1.6:1 for the 12,13- and 9,10-epoxides) was similar for both enzymes. When α-linolenic acid was the substrate, all three epoxides were produced in about equal ratios with both enzymes. In contrast for the ω-6 fatty acid, γ-linolenic acid, both enzymes produced only the 9,10- and 12,13-epoxldes. Furthermore, the ratio of the metabolites produced by each enzyme was significantly different. The ratios of 12,13-epoxide to 9,10-epoxide for γ-linolenic were 11.0 ± 0.19 and 5.8 ± 1.2 for P4502CAA and P4502C2, respectively. These results suggest that there may be subtle differences in the structure of 2C2 and 2CAA and also Indicate that P450 may be important in the generation of potentially active epoxide metabolites of unsaturated fatty acids other than arachidonic acid.

Original languageEnglish (US)
Pages (from-to)664-668
Number of pages5
JournalDrug Metabolism and Disposition
Volume24
Issue number6
StatePublished - Jun 1996

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Epoxidation
Epoxy Compounds
Cytochromes
Unsaturated Fatty Acids
alpha-Linolenic Acid
Metabolites
Enzymes
Fatty Acids
Linoleic Acid
Oleic Acid
Arachidonic Acid
Gas chromatography
Gas Chromatography-Mass Spectrometry
Mass spectrometry
Protein Isoforms
High Pressure Liquid Chromatography
Substrates

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Epoxidation of C18 unsaturated fatty acids by cytochromes P4502C2 and P4502CAA. / Laethem, Ronald M.; Balazy, Michael; Koop, Dennis.

In: Drug Metabolism and Disposition, Vol. 24, No. 6, 06.1996, p. 664-668.

Research output: Contribution to journalArticle

Laethem, Ronald M. ; Balazy, Michael ; Koop, Dennis. / Epoxidation of C18 unsaturated fatty acids by cytochromes P4502C2 and P4502CAA. In: Drug Metabolism and Disposition. 1996 ; Vol. 24, No. 6. pp. 664-668.
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