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The Biology of 5-Lipoxygenase: Function, Structure, and Regulatory Mechanisms

Authors

  • Eric S. Silverman,

    1. Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
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  • Jeffrey M. Drazen

    1. Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
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Address correspondence and reprint requests to: Jeffrey M. Drazen, M.D., Chief, Respiratory Disease Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.

Abstract

5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid to leukotriene A 4 (LTA 4). The first step consists of the oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and the second step is the dehydration of 5-HPETE to form LTA 4. These events are the first committed reactions leading to the synthesis of all leukotrienes and play a critical role in controlling leukotriene production. 5-LO has evolved many complex structural features and regulatory mechanisms to allow it to fulfill this highly specialized role. The biology of 5-LO is reviewed here with an emphasis on enzymatic function, protein and gene structure, essential cofactors, and the many regulatory mechanisms controlling its expression.

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