Demonstration of multiple regulatory factors for purified human leukocyte 5-lipoxygenase

The human leukocyte 5-lipoxygenase is a unique enzyme in its class because of its involvement in the synthesis of the biologically active leukotrienes. Furthermore, unlike most other lipoxygenases, this enzyme requires multiple stimulatory factors for maximal activity. These include Ca2+, ATP, and three non-dialyzable cellular components, two cytosolic, and one membrane-associated. The mechanism of action of these factors is not yet well understood; however, a Ca2+-dependent association of the enzyme and one of the cytosolic factors with the membrane has been demonstrated. These findings suggest that stimulation of the leukocyte, resulting in an increased intracellular Ca2+ concentration, may result in the translocation of the enzyme and the factor to a membrane site, thereby facilitating the interaction of these two proteins with other enzymes involved in the 20:4 metabolic cascade. The development of a better understanding of these processes should not only help to define the biochemical basis for the regulation of leukotriene formation, but should also yield valuable information concerning the more general aspects of stimulus-response coupling in the leukocyte.