TY - JOUR
T1 - Oxygenation of ω-3 fatty acids by human cytochrome P450 4F3B
T2 - Effect on 20-hydroxyeicosatetraenoic acid production
AU - Harmon, Shawn D.
AU - Fang, Xiang
AU - Kaduce, Terry L.
AU - Hu, Shanming
AU - Raj Gopal, V.
AU - Falck, J R
AU - Spector, Arthur A.
N1 - Funding Information:
This work was supported by Research Grants HL072845 (to A.A.S) and GM31278 (to J.R.F.), National Institutes of Health, 0230096N (to X.F.) from the American Heart Association, and the Robert A. Welch Foundation (to J.R.F.).
PY - 2006/9
Y1 - 2006/9
N2 - Cytochrome P450 (CYP) ω-oxidases convert arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a lipid mediator that modulates vascular tone. We observed that a microsomal preparation containing recombinant human CYP4F3B, which converts AA to 20-HETE, converted eicosapentaenoic acid (EPA) to 20-OH-EPA. Likewise, docosahexaenoic acid (DHA) was converted to 22-OH-DHA, indicating that human CYP4F3B also can oxidize 22-carbon ω-3 fatty acids. Consistent with these findings, addition of 0.5-5 μM EPA, DHA or ω-3 docosapentaenoic acid (DPA) to incubations containing 0.5 μM [3H]AA inhibited [3H]20-HETE production by 15-65%. [3H]20-OH-EPA was rapidly taken up by COS-7 cells, and almost all of the incorporated radioactivity remained as unmodified 20-OH-EPA. The 20-OH-EPA stimulated luciferase activity in COS-7 cells that express peroxisome proliferator-activated receptor α, indicating that this EPA metabolite may function as a lipid mediator. These findings suggest that some functional effects of ω-3 fatty acid supplementation may be due to inhibition of 20-HETE formation or the conversion of EPA to the corresponding ω-oxidized product.
AB - Cytochrome P450 (CYP) ω-oxidases convert arachidonic acid (AA) to 20-hydroxyeicosatetraenoic acid (20-HETE), a lipid mediator that modulates vascular tone. We observed that a microsomal preparation containing recombinant human CYP4F3B, which converts AA to 20-HETE, converted eicosapentaenoic acid (EPA) to 20-OH-EPA. Likewise, docosahexaenoic acid (DHA) was converted to 22-OH-DHA, indicating that human CYP4F3B also can oxidize 22-carbon ω-3 fatty acids. Consistent with these findings, addition of 0.5-5 μM EPA, DHA or ω-3 docosapentaenoic acid (DPA) to incubations containing 0.5 μM [3H]AA inhibited [3H]20-HETE production by 15-65%. [3H]20-OH-EPA was rapidly taken up by COS-7 cells, and almost all of the incorporated radioactivity remained as unmodified 20-OH-EPA. The 20-OH-EPA stimulated luciferase activity in COS-7 cells that express peroxisome proliferator-activated receptor α, indicating that this EPA metabolite may function as a lipid mediator. These findings suggest that some functional effects of ω-3 fatty acid supplementation may be due to inhibition of 20-HETE formation or the conversion of EPA to the corresponding ω-oxidized product.
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U2 - 10.1016/j.plefa.2006.05.005
DO - 10.1016/j.plefa.2006.05.005
M3 - Article
C2 - 16820285
AN - SCOPUS:33747874459
SN - 0952-3278
VL - 75
SP - 169
EP - 177
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
IS - 3
ER -