Cytochrome P450-dependent metabolism of omega-6 and omega-3 long-chain polyunsaturated fatty acids

Pharmacol Rep. 2010 May-Jun;62(3):536-47. doi: 10.1016/s1734-1140(10)70311-x.


Dietary fish oil omega-3 fatty acids (n-3 PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against arrhythmia and sudden cardiac death using largely unknown mechanisms. EPA and DHA may serve as efficient alternative substrates of arachidonic acid (AA) metabolizing cytochrome P450 (CYP) enzymes. For many of the CYP isoforms, the n-3 PUFAs are the preferred substrates. Moreover, the CYP enzymes oxygenate EPA and DHA with largely different regioselectivities compared to AA. In particular, the omega-3 double bond that distinguishes EPA and DHA from AA is a preferred site of CYP-catalyzed epoxidation reactions. Given the pivotal role of CYP-dependent AA metabolites in the regulation of vascular, renal and cardiac functions, their replacement by unique sets of epoxy- and hydroxy-metabolites derived from EPA and DHA may have far-reaching physiological implications. The currently available data suggest that some of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA.

Publication types

  • Review

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Cardiotonic Agents / metabolism
  • Cardiovascular Diseases / prevention & control
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP2E1 / metabolism
  • Cytochrome P-450 CYP2J2
  • Cytochrome P-450 Enzyme System / metabolism*
  • Death, Sudden, Cardiac / prevention & control
  • Docosahexaenoic Acids / metabolism
  • Docosahexaenoic Acids / pharmacology
  • Eicosapentaenoic Acid / metabolism
  • Eicosapentaenoic Acid / pharmacology
  • Epoxide Hydrolases / metabolism
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-6 / administration & dosage
  • Fatty Acids, Omega-6 / metabolism*
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism
  • Hydroxyeicosatetraenoic Acids / pharmacology


  • Cardiotonic Agents
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Hydroxyeicosatetraenoic Acids
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Cytochrome P-450 Enzyme System
  • Eicosapentaenoic Acid
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2J2
  • Epoxide Hydrolases