Cytochrome P450 and the Metabolism of Arachidonic Acid and Oxygenated Eicosanoids

  • Jorge H. Capdevila
  • Darryl Zeldin
  • Keiko Makita
  • Armando Karara
  • John R. Falck


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.


Arachidonic Acid Allene Oxide Microsomal Cytochrome Epoxyeicosatrienoic Acid Kidney Microsome 
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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Jorge H. Capdevila
    • 1
  • Darryl Zeldin
    • 2
  • Keiko Makita
    • 2
  • Armando Karara
    • 2
  • John R. Falck
    • 3
  1. 1.Departments of Medicine and BiochemistryVanderbilt University Medical SchoolNashvilleUSA
  2. 2.Department of MedicineVanderbilt University Medical SchoolNashvilleUSA
  3. 3.Department of Molecular GeneticsSouthwestern Medical CenterDallasUSA

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