REGULATION OF LEUKOTRIENE BIOSYNTHESIS

Leukotrienes are products of arachidonic acid metabolism derived through the action of the 5-lipoxygenase enzyme pathway. Leukotriene B-4 has been implicated as a mediator of inflammation through induction of leukocyte and lymphocyte activation. The cysteinyl leukotrienes are important mediators of immediate hypersensitivity reactions and initiate smooth muscle contraction. Regulation of the production of leukotrienes can be achieved either through the action of direct 5-lipoxygenase inhibitors or indirect leukotriene biosynthesis inhibitors which bind to 5-lipoxygenase activating protein. Leukotriene C-4 synthase and leukotriene A(4) hydrolase represent alternative enzymic targets within the biosynthetic cascade. Leukotriene receptor antagonists also have important therapeutic possibilities and in particular, leukotriene D-4 receptor antagonists have shown utility in the treatment of human bronchial asthma.