Biosynthesis of leukotriene B4

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.

Keywords: 5-Lipoxygenase (5-LOX); 5-Lipoxygenase-activating protein (FLAP); Arachidonic acid (AA); LTA(4) hydrolase (LTA(4)H); Leukotriene B(4) (LTB(4)).