Human 5-lipoxygenase associates with phosphatidylcholine liposomes and modulates LTA4 synthetase activity.
A Ca2+ and a phosphatidylcholine (PC) as stimulatory factors to human 5-lipoxygenase (5-LO) were assessed to examine aspects of the regulatory mechanism of 5-LO. In the presence of Ca2+ (1 microM or less), PC liposomes distinctly stimulated the dual activities of 5-LO for the production of 5-HPETE from arachidonate and for its subsequent conversion to LTA4. At the same concentration of Ca2+, 5-LO was found to bind to PC liposomes. As with 5-LO activities, the binding was dependent on the range of Ca2+ concentration. The conversion ratios of 5-HPETE to LTA4 were dependent on PC liposome concentration and reached a maximum of 50% conversion. Among the four cell membrane lipids examined, PC liposomes demonstrated the highest conversion ratio of 5-HPETE to LTA4 by 5-LO. Most of the arachidonate added to the reaction mixture localized in PC liposomes. These results confirm that the intracellular increase of Ca2+ concentration causes 5-LO to associate with the cell membrane and perform an interfacial reaction. They also suggest that this binding of 5-LO to the cell membrane enhances the subsequent conversion from 5-HPETE to LTA4.
Noguchi
M
M
Life Science Research Laboratory, Japan Tobacco Inc., Yokohama.
Miyano
M
M
Matsumoto
T
T
Noma
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D017572:Leukotriene A4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis; D008081:Liposomes / Q000378:metabolism / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*
D017572:Leukotriene A4; D015289:Leukotrienes; D008081:Liposomes; D010713:Phosphatidylcholines; D016718:Arachidonic Acid; C025348:arachidonic acid 5-hydroperoxide; D000255:Adenosine Triphosphate; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium