Biosynthesis of leukotriene B4 |
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| Affiliation: | 1. Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil;2. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil;3. Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil;1. Department of Medical Biochemistry and Biophysics, Scheeles väg 2, Karolinska Institutet, 17177 Stockholm, Sweden;2. Centre of Molecular Protein Science Lund University, Box 124, S-22100 Lund, Sweden |
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| Abstract: | Leukotriene B4 (LTB4) is a lipid mediator derived from arachidonic acid (AA) by the sequential action of 5-lipoxygenase (5-LOX), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H). It was initially recognized for its involvement in the recruitment of neutrophils and is one of the most potent chemotactic agents known to date. A large body of data has indicated that LTB4 plays a significant role in many chronic inflammatory diseases, such as arthritis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, cancer and more recently, metabolic disorder. In this review, we focus on the biosynthesis of LTB4 and its biological effects. In particular, we will describe a basic biochemical understanding integrated with recent developments in the field of structural biology of the three key enzymes (5-LOX, FLAP and LTA4H) in LTB4 biosynthesis, and also summarize the most outstanding work on in vivo biological and pathogenic roles of these enzymes and the development of enzyme inhibitors. |
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| Keywords: | Arachidonic acid (AA) 5-Lipoxygenase (5-LOX) 5-Lipoxygenase-activating protein (FLAP) |
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