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

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

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).

Keywords

Cysteine Flare Histamine Prostaglandin Proteinuria 

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Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • T. H. Lee
    • 1
    • 2
  • J. M. Drazen
    • 1
    • 3
    • 4
  • R. A. Lewis
    • 1
    • 2
  • K. F. Austen
    • 1
    • 2
  1. 1.Department of MedicineHarvard Medical SchoolBostonUSA
  2. 2.Departments of Rheumatology and ImmunologyBrigham and Women’s HospitalBostonUSA
  3. 3.Departments of Rheumatology and Immunology and of MedicineBrigham and Women’s HospitalBostonUSA
  4. 4.Department of PhysiologyHarvard School of Public HealthBostonUSA

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