Biosynthesis of Leukotriene B4 in Human Leukocytes
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).
KeywordsHuman Leukocyte Epoxide Hydrolase Microsomal Epoxide Hydrolase Arachidonate Metabolism Synthetic LTB4
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