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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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