Regulation of the production of Lipoxygenasf Products and the Role of Eicosanoids in Signal Transduction

  • Anthony Ford-Hutchinson
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

The leukotrienes are products of the metabolism of arachidonic acid through the 5-lipoxygenase enzyme pathway (Samuelsson, 1983; Ford-Hutchinson, 1985). This enzyme catalyses, first, the insertion of oxygen at carbon 5 to produce the intermediate, 5-hydroperoxy-6,8,11,14 eicosatetraenoic acid (5-HPETE) and, secondly, a dehydrase step which converts 5-HPETE to the unstable epoxide intermediate, 5,6-oxido- 7,9,11,14-eicosatetraenoic acid (leukotriene A4). Leukotriene A4 may then be converted either to 5S, 12R dihydroxy-6,8,10,14(Z,E,E,Z) eicosatetraenoic acid (leukotriene B4) by a specific enzyme, leukotriene A4 hydrolase (Radmark et al., 1984) or to 5-S-hydroxy-6R,S-glutathionyl-7,9,11,14-(E,E,Z,Z)-eicostetraenoic acid (leukotriene C4) by another specific enzyme, leukotriene C4 synthase (Bach et al., 1984). Subsequent metabolism of leukotriene C4 by membrane-bound γ-glutamyl transferase results in the formation of leukotriene D4 through cleavage of L-glutamic acid (Orning and Hammarstrom, 1980). Leukotriene D4 can then be converted to leukotriene E4 with loss of L-glycine by specific membrane-bound dipeptidases (Anderson et al., 1982).

Keywords

EDTA Leukemia Glutathione Catalysis Lipase 

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Anthony Ford-Hutchinson
    • 1
  1. 1.Department of PharmacologyMerck Frosst Centre for Therapeutic ResearchPointe Claire-DorvalCanada

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