5-Lipoxygenase: enzyme expression and regulation of activity

Pharm Acta Helv. 1994 Jul;69(1):3-14. doi: 10.1016/0031-6865(94)90024-8.

Abstract

5-Lipoxygenase catalyzes the transformation of arachidonic acid to leukotriene A4. This unstable intermediate can be converted to leukotriene B4 by LTA4-hydrolase or to leukotriene C4 by LTC4-synthase. Leukotrienes are involved in host defense reactions and play an important role in inflammatory diseases like asthma, inflammatory bowel disease and arthritis. The capability to release leukotrienes is restricted to a few cell types. Under pathophysiological conditions, leukotrienes are released from granulocytes, mast cells or macrophages. During hematopoiesis the competence of these cells for leukotriene biosynthesis is supposed to be upregulated. In mature cells, 5-lipoxygenase activity is tightly regulated and seems to be under the control of additional cellular components. One cellular component, a membrane-bound peptide termed FLAP, which is necessary for 5-LO activity in intact cells has been recently identified. Inhibitors of FLAP function prevent translocation of 5-lipoxygenase from cytosol to the membrane and inhibit 5-LO activation. Thus, the understanding of the regulatory mechanisms of cellular leukotriene biosynthesis provides new concepts for the development of antiinflammatory drugs. This review focuses on the regulation of gene expression and activity of 5-lipoxygenase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / biosynthesis
  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Humans
  • Leukotrienes / metabolism
  • Lipoxygenase Inhibitors / pharmacology

Substances

  • Leukotrienes
  • Lipoxygenase Inhibitors
  • Arachidonate 5-Lipoxygenase