DISCOVERY OF A 2ND 15S-LIPOXYGENASE IN HUMANS

The lipoxygenase metabolism of arachidonic acid occurs in specific blo od cell types and epithelial tissues and is activated in inflammation and tissue injury, In the course of studying lipoxygenase expression i n human skin, we detected and characterized a previously unrecognized enzyme that at least partly accounts for the 15S-lipoxygenase metaboli sm of arachidonic acid in certain epithelial tissues, The cDNA was clo ned from human hair roots, and expression of the mRNA was detected als o in prostate, lung, and cornea; an additional 16 human tissues, inclu ding peripheral blood leukocytes, were negative for the mRNA. The cDNA encodes a protein of 676 amino acids with a calculated molecular mass of 76 kDa, The amino acid sequence has approximately 40% identity to the known human 55-, 12S-, acid 15S-lipoxygenases, When expressed in H EK 293 cells, the newly discovered enzyme converts arachidonic acid ex clusively to 15S-hydroperoxeicosatetraenoic acid, while linoleic acid is less well metabolized, These features contrast with the previously reported 15S-lipoxygenase, which oxygenates arachidonic acid mainly at C-15, but also partly at C-12, and for which linoleic acid is an exce llent substrate. The different catalytic activities and tissue distrib ution suggest a distinct function for the new enzyme compared with the previously reported human 15S-lipoxygenase.