TY - JOUR
T1 - Epoxidation of C18 unsaturated fatty acids by cytochromes P4502C2 and P4502CAA
AU - Laethem, Ronald M.
AU - Balazy, Michael
AU - Koop, Dennis R.
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 1996/6
Y1 - 1996/6
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8781783
AN - SCOPUS:0029659002
SN - 0090-9556
VL - 24
SP - 664
EP - 668
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 6
ER -