Structure, Function, and Regulation of Leukotriene A4 Hydrolase

Leukotrienes are important chemical mediators in a variety of inflammatory and allergic conditions, including those affecting the respiratory system. These signaling molecules can be divided into two groups: the proinflammatory leukotriene B 4 (LTB 4 ) and the spasmogenic leukotrienes C 4 . D 4 , and E 4 , also termed cysteinyl-leukotrienes (1). LTB 4 is one of the most powerful chemotactic agents known to date and acts via specific seven-transmembrane, G protein-coupled surface receptors on the target cells (2). The profile of the biological properties of LTB 4 makes it a key component in the complex network of soluble and cell-bound factors that govern the development and maintenance of inflammation. Hence, LTB 4 has been proposed to play a role in a variety of acute and chronic inflammatory diseases such as arthritis, dermatoses, inflammatory bowel disease (IBD), and chronic obstructive pulmonary disease (COPD). In particular, LTB 4 seems to play a role in the recruitment of inflammatory cells to the site of tissue injury. This article gives a brief overview of the biochemistry and molecular biology of LTA 4 hydrolase, the enzyme catalyzing the final step in the biosynthesis of LTB 4 .