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Journal of Lipid Research, Vol. 41, 163-181, February 2000
Copyright © 2000 by Lipid Research, Inc.

Review

Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase

Jorge H. Capdevilaa,b, John R. Falckc, and Raymond C. Harrisa
a Departments of Medicine, Vanderbilt University Medical School, Nashville, TN 372323
b Biochemistry, Vanderbilt University Medical School, Nashville, TN 372323
c Department of Biochemistry, University of Texas Southwestern Medical School, Dallas, TX 75235

Correspondence to: Jorge H. Capdevila

The demonstration of in vivo arachidonic acid epoxidation and {omega}-hydroxylation established the cytochrome P450 epoxygenase and {omega}/{omega};–1 hydroxylase as formal metabolic pathways and as members of the arachidonate metabolic cascade. The characterization of the potent biological activities associated with several of the cytochrome P450-derived eicosanoids suggested new and important functional roles for these enzymes in cellular, organ, and body physiology, including the control of vascular reactivity and systemic blood pressures. Past and current advances in cytochrome P450 biochemistry and molecular biology facilitate the characterization of cytochrome P450 isoforms responsible for tissue/organ specific arachidonic acid epoxidation and {omega}/{omega}– 1 hydroxylation, and thus, the analysis of cDNA and/or gene specific functional phenotypes. The combined application of physiological, biochemical, molecular, and genetic approaches is beginning to provide new insights into the physiological and/or pathophysiological significance of these enzymes, their endogenous substrates, and products.—Capdevila, J. H., J. R. Falck, and R. C. Harris. Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase. J. Lipid Res. 2000. 41: 163–181.

Supplementary key words: cytochrome P450, fatty acid hydroxylase, arachidonic acid, eicosanoids, arachidonic acid monooxygenase, arachidonic acid epoxygenase, EET, HETE, salt sensitivity, hypertension, hyperpolarizing factor, EDHF


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Mol. Pharmacol., April 1, 2002; 61(4): 840 - 852.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. B. Jump
The Biochemistry of n-3 Polyunsaturated Fatty Acids
J. Biol. Chem., March 8, 2002; 277(11): 8755 - 8758.
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 HypertensionHome page
B. Lauterbach, E. Barbosa-Sicard, M.-H. Wang, H. Honeck, E. Kargel, J. Theuer, M. L. Schwartzman, H. Haller, F. C. Luft, M. Gollasch, et al.
Cytochrome P450-Dependent Eicosapentaenoic Acid Metabolites Are Novel BK Channel Activators
Hypertension, February 1, 2002; 39(2): 609 - 613.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
I. Fleming
Cytochrome P450 and Vascular Homeostasis
Circ. Res., October 26, 2001; 89(9): 753 - 762.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
V. R. Holla, F. Adas, J. D. Imig, X. Zhao, E. Price Jr., N. Olsen, W. J. Kovacs, M. A. Magnuson, D. S. Keeney, M. D. Breyer, et al.
Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension
PNAS, April 24, 2001; 98(9): 5211 - 5216.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
F. Coceani
Carbon Monoxide in Vasoregulation : The Promise and the Challenge
Circ. Res., June 23, 2000; 86(12): 1184 - 1186.
[Full Text] [PDF]

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 J. Biol. Chem.Home page
U. Hoch, J. R. Falck, and P. R. O. de Montellano
Molecular Basis for the omega -Regiospecificity of the CYP4A2 and CYP4A3 Fatty Acid Hydroxylases
J. Biol. Chem., August 25, 2000; 275(35): 26952 - 26958.
[Abstract] [Full Text] [PDF]

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C. J. Sinal, M. Miyata, M. Tohkin, K. Nagata, J. R. Bend, and F. J. Gonzalez
Targeted Disruption of Soluble Epoxide Hydrolase Reveals a Role in Blood Pressure Regulation
J. Biol. Chem., December 15, 2000; 275(51): 40504 - 40510.
[Abstract] [Full Text] [PDF]

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X. Fang, T. L. Kaduce, N. L. Weintraub, S. Harmon, L. M. Teesch, C. Morisseau, D. A. Thompson, B. D. Hammock, and A. A. Spector
Pathways of Epoxyeicosatrienoic Acid Metabolism in Endothelial Cells. IMPLICATIONS FOR THE VASCULAR EFFECTS OF SOLUBLE EPOXIDE HYDROLASE INHIBITION
J. Biol. Chem., April 27, 2001; 276(18): 14867 - 14874.
[Abstract] [Full Text] [PDF]

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D. C. Zeldin
Epoxygenase Pathways of Arachidonic Acid Metabolism
J. Biol. Chem., September 21, 2001; 276(39): 36059 - 36062.
[Full Text] [PDF]


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