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Journal of Lipid Research, Vol. 41, 163-181, February 2000
Copyright © 2000 by Lipid Research, Inc.
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 -hydroxylation established the cytochrome P450 epoxygenase and / ;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 / 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: 163181.
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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K. M. Gauthier, C. Deeter, U. M. Krishna, Y. K. Reddy, M. Bondlela, J.R. Falck, and W. B. Campbell
14,15-Epoxyeicosa-5(Z)-enoic Acid: A Selective Epoxyeicosatrienoic Acid Antagonist That Inhibits Endothelium-Dependent Hyperpolarization and Relaxation in Coronary Arteries
Circ. Res.,
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[Abstract]
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Q. Xie, Y. Zhang, C. Zhai, and J. A. Bonanno
Calcium Influx Factor from Cytochrome P-450 Metabolism and Secretion-like Coupling Mechanisms for Capacitative Calcium Entry in Corneal Endothelial Cells
J. Biol. Chem.,
May 3, 2002;
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L. M. King, J. Ma, S. Srettabunjong, J. Graves, J. A. Bradbury, L. Li, M. Spiecker, J. K. Liao, H. Mohrenweiser, and D. C. Zeldin
Cloning of CYP2J2 Gene and Identification of Functional Polymorphisms
Mol. Pharmacol.,
April 1, 2002;
61(4):
840 - 852.
[Abstract]
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D. B. Jump
The Biochemistry of n-3 Polyunsaturated Fatty Acids
J. Biol. Chem.,
March 8, 2002;
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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):
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[Abstract]
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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;
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5211 - 5216.
[Abstract]
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F. Coceani
Carbon Monoxide in Vasoregulation : The Promise and the Challenge
Circ. Res.,
June 23, 2000;
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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
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August 25, 2000;
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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;
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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
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April 27, 2001;
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[Abstract]
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D. C. Zeldin
Epoxygenase Pathways of Arachidonic Acid Metabolism
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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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