| Arachidonic acid is also converted into other inflammatory and vasoactive mediators, called leukotrienes, by the action of a variety of structurally related lipoxygenases (see Fig. 38.13). For example, 5-lipoxygenase comprises both a dioxygenase activity that converts arachidonate to 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and a dehydrase activity that transforms 5-HPETE to leukotriene A4 (LTA4). Natural deficiencies in lipoxygenases have been associated with human disease: for example, in one study, 40% of patients with myeloproliferative disorders were found to have reduced platelet lipoxygenase activity and increased synthesis of thromboxane. In addition, mice deficient in 5-lipoxygenase exhibit defects in the responses of their neutrophils to immune complexes and platelet-activating factor, supporting the idea that leukotrienes have important roles in inflammatory responses.
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