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Biosynthesis of Leukotriene B4 in Human Leukocytes

Demonstration of a Calcium-Dependent 5-Lipoxygenase
  • Rodger M. McMillan
  • David J. Masters
  • Wayne W. Sterling
  • Peter R. Bernstein
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Arachidonate metabolism via 5-lipoxygenase leads to formation of a family of biologically active molecules, the leukotrienes. The first step in leukotriene biosynthesis is catalyzed by the enzyme 5-lipoxygenase and results in formation of 5-hydroperoxy-6, 8, 11, 14-eicosatetraenoic acid (5-HPETE), which may be converted enzymatically (via the action of a peroxidase) or nonenzymically to the corresponding hydroxy acid, 5-hydroxy-6, 8, 11, 14-eicosatetraenoic acid (5-HETE). Alternatively, 5-HPETE may undergo enzymatic dehydration to form an unstable epoxide, 5, 6-epoxy-7, 9, 11, 14-eicosatetraenoic acid, which is termed leukotriene A4 (LTA4). Enzymatic hydrolysis of LTA4 yields 5S, 12R-dihydroxy-6, 14-cis-8, 10-trans-eicosatetraenoic acid (leukotriene B4, LTB4), which is a potent, stereospecific activator of a variety of human neutrophil responses, including chemokinesis, chemotaxis, and aggregation (Ford-Hutchinson et al., 1980; Goetzl and Pickett, 1981; Malmsten et al., 1980).

Keywords

Human Leukocyte Epoxide Hydrolase Microsomal Epoxide Hydrolase Arachidonate Metabolism Synthetic LTB4 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Rodger M. McMillan
    • 1
  • David J. Masters
    • 1
  • Wayne W. Sterling
    • 1
  • Peter R. Bernstein
    • 2
  1. 1.ICI Pharmaceuticals DivisionMeresideMacclesfield, CheshireUK
  2. 2.Medicinal Chemistry Department, Stuart PharmaceuticalsDivision of ICI Americas Inc.WilmingtonUSA

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