[Modulation of leukotriene pathway - potential targets]

Abstract

Leukotrienes (LT), namely cysteinyl LT and LTB4, are potent lipid mediators taking part in the signal pathways of many inflammatory processes. The arachidonic acid transformation into leukotrienes can be signed as the leukotriene pathway. The key enzyme is 5-lipoxygenase, a dioxygenase containing a nonheme-bound ferric central ion, which in the catalytic complex with 5-lipoxygenase activating protein forms 5-hydroperoxyeicosatetraenoic acid. In the next steps this process involves leukotriene A4-hydrolase or leukotriene C4-synthase. According to the progress in recent years in the area of X-ray structural analysis and revealed 3D structure of these biocatalysts, especially their active sites, the development of new drugs markedly accelerated. This complicated enzymatically controlled process offers several possibilities of modulation and presents new approaches to the treatment of typical inflammatory diseases as well as in the therapy of atherosclerosis and cancer.