Phospholipids are possible regulators of lipoxygenase reaction on membrane level

Products of lipoxygenase (LO) cascade polyunsaturated fatty acids oxidation - leukotrienes, lipoxins - are known as potent modulators of cell proliferation taking part in cancerogenesis, reticulocyte membrane degradation, etc. Despite of high biological activity of these compounds the mechanism of LO regulation in vivo is not clear. In present study we have studied whether the composition of membrane phospholipids is able to regulate LO reaction. For this purpose LO reaction has been investigated on different models of phospholipid membrane. In our experiments phospholipid liposomes and membrane models based on chemically modified silica have been used. We have demonstrate that increasing of phosphatidylinositol/phosphatidylcholin molar ratio in membrane model leads to LO activation. This phenomenon accompanied by product inhibition effect when sufficient level of the latter has been reached. Kinetic analysis of die reaction on membrane from pure phosphatidylinositol with linoleic acid (LA) added as a substrate shows that 5-LO has much more affinity level to product of the reaction than to LA. The investigations of fatty acids ionisation and pH-dependence of the reaction allow us to suggest that the charge of phospholipid polar group play a crucial role in regulation of lipoxygenase reaction on membrane model. It is possible that changes in phospholipid composition in biological membranes in vivo caused by phospholipases can regulate lipoxygenase activity.