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Cytochrome P450 and the Metabolism of Arachidonic Acid and Oxygenated Eicosanoids

  • Chapter
Cytochrome P450

Abstract

Eukaryotic cells contain substantial amounts of arachidonic acid (AA; 5,8,11,14-eicosatetraenoic acid) esterified predominantly to the sn-2 position of cellular glycerophospholipids. As with many lipid-derived mediators, e.g., cholesterol, phosphoinositides, diglycerides, AA serves a structural role, as a component of cellular membranes, and an important functional role, as a participant in a variety of receptor/agonist-mediated signaling cascades.1–4 In the absence of stimuli, the intracellular levels of nonesterified AA are nearly undetectable. However, most organ cells possess an elaborate enzymatic machinery that, in response to a variety of stimuli, catalyzes: (1) the hydrolytic cleavage of the AA molecule form selected, hormonally sensitive phospholipid pools, (2) the transduction of chemical information into the fatty acid molecular template by means of regio- and stereospecific oxygenation reactions, and (3) the decoding of that chemical information either by receptor-mediated processes or, alternatively, by the direct effects of these oxygenated metabolites on metabolic pathways1–4 (Fig. 1). As a net result, these processes provide cells with a rapid and versatile on/off molecular switch for the intra- or intercellular transduction and/or amplification of functionally meaningful information.

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Authors and Affiliations

  1. Departments of Medicine and Biochemistry, Vanderbilt University Medical School, Nashville, Tennessee, 37232, USA

    Jorge H. Capdevila

  2. Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee, 37232, USA

    Darryl Zeldin, Keiko Makita & Armando Karara

  3. Department of Molecular Genetics, Southwestern Medical Center, Dallas, Texas, 75235, USA

    John R. Falck

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  1. Jorge H. Capdevila
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  2. Darryl Zeldin
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  3. Keiko Makita
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  4. Armando Karara
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  5. John R. Falck
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  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, 94143, San Francisco, California, USA

    Paul R. Ortiz de Montellano

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Capdevila, J.H., Zeldin, D., Makita, K., Karara, A., Falck, J.R. (1995). Cytochrome P450 and the Metabolism of Arachidonic Acid and Oxygenated Eicosanoids. In: de Montellano, P.R.O. (eds) Cytochrome P450. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2391-5_13

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  • DOI: https://doi.org/10.1007/978-1-4757-2391-5_13

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