Čes. slov. farm. 2012, 61(3):101-106

Modulation of leukotriene pathway - potential targets

Peter Hoffman^*, Lýdia Bezáková

Univerzita Komenského v Bratislave, Farmaceutická fakulta, Katedra bunkovej a molekulárnej biológie liečiv

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.

Keywords: leukotrienes; 5-lipoxygenase; modulation; leukotriene pathway

Received: April 4, 2012; Accepted: May 9, 2012; Published: March 1, 2012  Show citation