Mammalian arachidonate 15-lipoxygenases structure, function, and biological implications

Abstract

Lipoxygenases (LOXs) constitute a heterogeneous family of lipid peroxidizing enzymes capable of oxygenating polyunsaturated fatty acids to their corresponding hydroperoxy derivatives. In mammals, LOXs are classified with respect to their positional specificity of arachidonic acid oxygenation into 5-, 8-, 12-, and 15-LOXs. Arachidonate 15-LOXs may be sub-classified into a reticulocyte-type (type-1) and an epidermis-type (type-2) enzyme. Since the leukocyte-type 12-LOXs are very similar to the reticulocyte-type 15-LOXs, these enzymes are designated 12/15-LOXs. Several LOX isoforms, in particular the reticulocyte-type 15-LOX and the human 5-LOX, are well characterized with respect to their structural and functional properties On the other hand, the biological role of most LOX-isozymes including the reticulocyte-type 15-LOC is far from clear. This review is intended to summarize the recent developments in 15-LOX research with particular emphasis to molecular enzymology and regulation of gene expression. In addition, the major hypotheses on the physiological and patho-physiological roles of 15-LOXs will be discussed briefly.