ABSTRACT

Introduction/Historical Perspective Lipoxygenases (LOX) are a class of dioxygenase enzymes containing a catalytic nonheme, nonsulfur iron atom. They catalyze the stereospecific insertion of molecular oxygen into polyunsaturated fatty acids containing an unconjugated (Z,Z)- 1,4-pentadiene moiety. The products formed are optically active (S)- or (R)-hydroperoxides. They are widely distributed throughout the plant and animal kingdoms (1,2). Early studies of mammalian lipoxygenases focused primarily on the enzymes found in different blood cell types and thus were categorized into three main groups according to their positional specificity with respect to arachidonic acid (AA) (3). The three groups are the 5-lipoxygenase (associated mainly with neutrophils), 12-lipoxygenase (associated mainly with platelets), and 15-lipoxygenase (associated mainly with reticulocytes). It has now become clear that this classification and distribution is limiting because hydroxyeicosatetraenoic acids (HETE), products of AA metabolism, have been identified in many different cells from invertebrates to human beings. Many recent studies have reported abundant HETE formation in a variety of tissue injuries, tumors, and inflammatory processes.