Oxygenation of ω-3 fatty acids by human cytochrome P450 4F3B: Effect on 20-hydroxyeicosatetraenoic acid production

Shawn D. Harmon, Xiang Fang, Terry L. Kaduce, Shanming Hu, V. Raj Gopal, J R Falck, Arthur A. Spector

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume75
Issue number3
DOIs
StatePublished - Sep 2006

Fingerprint

Eicosapentaenoic Acid
Oxygenation
Cytochrome P-450 Enzyme System
Fatty Acids
Docosahexaenoic Acids
Arachidonic Acid
COS Cells
Lipids
Peroxisome Proliferator-Activated Receptors
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Radioactivity
Electron Transport Complex IV
Metabolites
Luciferases
Blood Vessels
Oxidoreductases
Carbon
hydroxide ion

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Oxygenation of ω-3 fatty acids by human cytochrome P450 4F3B : Effect on 20-hydroxyeicosatetraenoic acid production. / Harmon, Shawn D.; Fang, Xiang; Kaduce, Terry L.; Hu, Shanming; Raj Gopal, V.; Falck, J R; Spector, Arthur A.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 75, No. 3, 09.2006, p. 169-177.

Research output: Contribution to journalArticle

Harmon, Shawn D. ; Fang, Xiang ; Kaduce, Terry L. ; Hu, Shanming ; Raj Gopal, V. ; Falck, J R ; Spector, Arthur A. / Oxygenation of ω-3 fatty acids by human cytochrome P450 4F3B : Effect on 20-hydroxyeicosatetraenoic acid production. In: Prostaglandins Leukotrienes and Essential Fatty Acids. 2006 ; Vol. 75, No. 3. pp. 169-177.
@article{caf787c759d84ad5a9f6085f15eb1bb8,
title = "Oxygenation of ω-3 fatty acids by human cytochrome P450 4F3B: Effect on 20-hydroxyeicosatetraenoic acid production",
abstract = "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.",
author = "Harmon, {Shawn D.} and Xiang Fang and Kaduce, {Terry L.} and Shanming Hu and {Raj Gopal}, V. and Falck, {J R} and Spector, {Arthur A.}",
year = "2006",
month = "9",
doi = "10.1016/j.plefa.2006.05.005",
language = "English (US)",
volume = "75",
pages = "169--177",
journal = "Prostaglandins Leukotrienes and Essential Fatty Acids",
issn = "0952-3278",
publisher = "Churchill Livingstone",
number = "3",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=33747874459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747874459&partnerID=8YFLogxK

U2 - 10.1016/j.plefa.2006.05.005

DO - 10.1016/j.plefa.2006.05.005

M3 - Article

C2 - 16820285

AN - SCOPUS:33747874459

VL - 75

SP - 169

EP - 177

JO - Prostaglandins Leukotrienes and Essential Fatty Acids

JF - Prostaglandins Leukotrienes and Essential Fatty Acids

SN - 0952-3278

IS - 3

ER -