Therapeutic Aspects of Leukotriene Antagonists and Inhibitors

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


The metabolism of arachidonic acid by the 5-lipoxygenase enzyme system results in the production of leukotrienes (Ford-Hutchinson, 1990a). 5-lipoxygenase is only present in cells of the myeloid lineage, including inflammatory cells such as polymorphonuclear leukocytes, eosinophils, mast cells and macrophages. Cellular activation induces a rise in intracellular calcium leading to an activation and translocation from the cytosol to the membrane fraction of both phospholipase A2 and 5-lipoxygenase (Rouzer and Kargman, 1988; Clark et al., 1991). Activation of 5-lipoxygenase is associated with the presence of a novel membrane protein, 5-lipoxygenase activating protein (FLAP) (Dixon et al., 1990; Miller et al., 1990). The end product of metabolism of arachidonic acid by the 5-lipoxygenase enzyme is leukotriene A4, an unstable epoxide intermediate. Further metabolism of leukotriene A4 can occur through, first, leukotriene A4 hydrolase, to produce the dihydroxy fatty acid, leukotriene B4, and, secondly, through leukotriene C4 synthase, to produce the glutathione conjugate, leukotriene C4 (Ford-Hutchinson, 1990a). Leukotriene C4 can then be converted to leukotriene D4 through loss of L-glutamic acid by the action of γ-glutamyl transferase. Leukotriene D4 in turn can be further metabolized by peptidases through loss of glycine to produce leukotriene E4.


Allergic Conjunctivitis Human Bronchial Asthma Dihydroxy Fatty Acid Nonnal Volunteer Dimethylpropanoic Acid 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • A. W. Ford-Hutchinson
    • 1
  1. 1.Merck Frosst Centre for Therapeutic ResearchQuebecCanada

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