Cell biology of the 5-lipoxygenase pathway.
The initial enzymatic steps in leukotriene synthesis occur at the nuclear envelope. Cytosolic phospholipase A2 translocates from the cytoplasm to selectively hydrolyze nuclear envelope phospholipids, releasing free arachidonate. 5-Lipoxygenase-activating protein, an arachidonate transfer protein, then binds arachidonate and presents it to 5-lipoxygenase (5-LO), which catalyzes a two-step reaction to produce leukotriene A4. In resting human and rat peripheral blood neutrophils, 5-LO is localized to the cytoplasm; in rat basophilic leukemia cells and human alveolar macrophages, however, it is found predominantly in the nucleus. Immunofluorescence microscopy studies demonstrate that both cytoplasmic and nuclear 5-LO move to the nuclear envelope following cell activation. Many questions remain unanswered regarding the significance of nuclear 5-LO, potential autocrine actions of leukotrienes, and intracellular trafficking of these enzymes and their products.
Peters-Golden
M
M
University of Michigan Medical Center, Ann Arbor 48109-0642, USA.
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D006801:Humans; D017572:Leukotriene A4 / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism
D017572:Leukotriene A4; D015289:Leukotrienes; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017997:Leukotriene C4; D001094:Arachidonate 5-Lipoxygenase