Evidence for a leukotriene A4 hydrolase in Xenopus laevis skin exudate

Leukotriene A4 hydrolase is a cytosolic metalloenzyme of the arachidonic acid biosynthetic pathway responsible for leukotriene A4 conversion into leukotriene B4. In addition to its epoxide hydrolase properties, this enzyme exhibits an aminopeptidase activity which was used as an assay to monitor the purification of a novel form of leukotriene A4 hydrolase from Xenopus laevis skin exudate. This 70 kDa, secreted, form of leukotriene A4 hydrolase was identified by immunochemical cross-reactivity with anti-human leukotriene A4 hydrolase antibodies and by its capacity to convert leukotriene A4 into leukotriene B4. Moreover this enzyme produced a second metabolite which could be the leukotriene B4 isomer 5S,12R-dihydroxy-6,10-trans-8,14-4-cis-eicosatetraenoic acid, previously shown by Strömberg et al. (Eur.J. Biochem. 238 (1996) 599-605) to be formed by incubation of the leukotriene A4 with amphibian tissue extracts. Partial amino acid sequencing of peptides generated by endolysin C fragmentation of the purified enzyme confirmed the presence, in X. laevis skin secretions, of a related but distinct form of leukotriene A4 hydrolase which is likely to be responsible for the production of these eicosanoid metabolites of leukotriene A4.