Enzymes functional in the syntheses of leukotrienes and related compounds

1. Leukotrienes (LT) constitute a family of bioactive compounds mainly involved in inflammatory and immunological responses. 2. LTs are produced via an unstable intermediate, LTA4 which is synthesized by the action of arachidonate 5-lipoxygenase, a calcium-dependent enzyme. 3. LTA4 is converted to either LTB4 by cytosolic LTA4 hydrolase or to LTC4 by LTC4 synthase present in the microsomal fraction. 4. Three enzymes (5-lipoxygenase, LTA4 hydrolase and LTC4 synthase) were purified, and molecular and kinetic properties have been extensively investigated. 5. The cDNA of LTA4 hydrolase was recently isolated, and the primary structure was fully determined in our laboratory. 6. I report herein recent progress in studies on arachidonic acid metabolism, with the focus primarily on enzymes linked to the 5-lipoxygenase pathway.