Roles of lipid-modulating enzymes diacylglycerol kinase and cyclooxygenase under pathophysiological conditions

Lipid not only represents a constituent of the plasma membrane, but also plays a pivotal role in intracellular signaling. Lipid-mediated signaling system is strictly regulated by several enzymes, which act at various steps of the lipid metabolism. Under pathological conditions, prolonged or insufficient activation of this system results in dysregulated signaling, leading to diseases such as cancer or metabolic syndrome. Of the lipid-modulating enzymes, diacylglycerol kinase (DGK) and cyclooxygenase (COX) are intimately involved in the signaling system. DGK consists of a family of enzymes that phosphorylate a second messenger diacylglycerol (DG) to produce phosphatidic acid (PA). Both DG and PA are known to activate signaling molecules such as protein kinase C. COX catalyzes the committed step in prostanoid biosynthesis, which involves the metabolism of arachidonic acid to produce prostaglandins. Previous studies have shown that the DGK and COX are engaged in a number of pathological conditions. This review summarizes the functional implications of these two enzymes in ischemia, liver regeneration, vascular events, diabetes, cancer and inflammation.