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Substrate and regulatory functions of eicosapentaenoic and docosahexaenoic acids for the 5-lipoxygenase pathway

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IUPHAR 9th International Congress of Pharmacology London 1984

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Abstract

Arachidonic acid (AA) released from membrane phospholipids by phospholipases during cell activation may be oxidatively metabolized by the enzymes of the cyclo-oxygenase or the 5-lipoxygenase pathway. The 5-lipoxygenase pathway, which exhibits a more limited cellular distribution than the cyclooxygenase pathway (Samuelsson et al., 1978; Lewis & Austen, 1984), generates 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HPETE) from AA. 5-HPETE is reduced to 5(S)-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE) (Borgeat & Samuelsson, 1979a) or is converted to an epoxide, 5,6-oxido-7,9-trans-11,14-cis-eicosatetraenoic acid (leukotriene A4, LTA4) (Borgeat & Samuelsson, 1979b; Rådmark et al., 1980; Hammarstrom & Samuelsson, 1980). LTA4 is processed by an epoxide hydrolase to 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4) Borgeat & Samuelsson, 1979c) or by a glutathione-S-transferase to 5(S)-hydroxy-6R-(S)-glutathionyl-7,9-trans-11,14,-cis-eicosatetraenoic acid (LTC4) (Murphy et al., 1979; Bach et al., 1980).

Presented in part at the Symposium on n-3 Fatty Acids, Reading, England, July, 1984. Correspondence: Dr. Lee, The Seeley G. Mudd Bldg., Room 610, 250 Longwood Ave., Boston, MA 02115.

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Authors and Affiliations

  1. Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA

    T. H. Lee, J. M. Drazen, R. A. Lewis & K. F. Austen

  2. Departments of Rheumatology and Immunology, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    T. H. Lee, R. A. Lewis & K. F. Austen

  3. Departments of Rheumatology and Immunology and of Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    J. M. Drazen

  4. Department of Physiology, Harvard School of Public Health, Boston, MA, 02115, USA

    J. M. Drazen

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William Paton James Mitchell Paul Turner Cheryl Padgham Eileen Ashcroft

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Lee, T.H., Drazen, J.M., Lewis, R.A., Austen, K.F. (1984). Substrate and regulatory functions of eicosapentaenoic and docosahexaenoic acids for the 5-lipoxygenase pathway. In: Paton, W., Mitchell, J., Turner, P., Padgham, C., Ashcroft, E. (eds) IUPHAR 9th International Congress of Pharmacology London 1984. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-17615-1_9

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