Animal Lipoxygenases – Structure, Positional Specificity of Lipoxygenase Isoenzymes and Their Importance
a Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University,b Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University
Keywords: structure of lipoxygenases, lipoxygenase isoenzymes, gene mutation, polyunsaturated fatty acids, lipoxygenase inhibitors
Lipoxygenases (LOX) constitute a heterogeneous family of lipid peroxidizing enzymes which catalyze the stereospecific insertion of molecular oxygen into polyunsaturated fatty acids. The primary products of LOX reaction are hydroperoxy fatty acids, which are rapidly reduced to the corresponding hydroxy derivatives. In mammalian organisms, there are 4 main LOX isoforms, 5-LOX, 8-LOX, 12-LOX, 15-LOX, constituting hydroperoxides with positional and stereo specificity. In the subsequent metabolic processes they provide significant cell signaling molecules and secondary messengers taking part in the development of inflammatory, tumorous and other diseases.
Recent studies clarified the role of lipoxygenases in various diseases. The study of the structure and the active site of enzyme, preparation of recombinant forms with the targeted gene mutations have shown possibilities for better understanding the lipoxygenase role in various pathological processes. Searching for selective inhibitors of LOX isoenzymes is an active area of investigation. They can represent an important research tool or become a promising targeted therapy of a wide range of human diseases.
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