Catabolism of leukotriene A4 into B4, C4, and D4 by rat liver subcellular fractions

3H]Leukotriene A4 was incubated with various subcellular fractions of rat liver homogenates. After solvent extraction and purification on C18 Sep-Pak cartridges, tritiated products migrating on reversed-phase HPLC with authentic unlabelled leukotriene C4, D4 and B4 were observed. The identity of leukotriene C4 was confirmed through enzymatic conversion into D4 by gamma-glutamyl transpeptidase as well as by bioassay on the rat stomach fundus after HPLC purification. The contractile response to the extracted material was blocked by the SRS antagonist, FPL 55712. Leukotriene B4 synthesis was located in the 100 000 X g supernatant, while C4 synthesis was present in the corresponding pellet. Leukotriene C4 formation was enhanced when reduced glutathione was supplemented in the incubation medium. These results demonstrate the presence in rat liver of various enzymatic steps in leukotriene A4 catabolism.