Hexadecylphosphocholine as an Useful Tool for Investigating Phosphatidylcholine Biosynthesis and Sorting

Abstract

Phosphatidylcholine is the most abundant phospholipid in mammalian tissues. The main route of its biosynthesis is the CDP-choline pathway with CTP : choline phosphate cytidylyltransferase (CT) (EC 2.7.7.15) as the rate-limiting enzyme ( for review see Vance, 1990). Recently, we report about a new inhibitor of this pathway hexadecylphosphocholine (HePC), which directly inhibits the CT (Haase et al., 1990: Geilen et al.. 1991). HePC belongs to the group of alkylphosphocholines, which are structurally different from the well known alkyllysophosphoglycerides and acyllysophosphoglycerides. Figure 1 shows the chemical structure of HePC. Treatment of MDCK cells with micromolar concentrations of HePC leads to an in-hibition of the phosphatidylcholine bio-synthesis without an effect on the other phospholipid classes. This inhibition is paralleled by the disturbance of the translocation of CT. This enzyme is inactive in the lipid-free, cytosolic form. Therefore, HePC may serve as an useful tool for investigating processes in which phosphatidylcholine is involved. Figure 2 shows the inhibitory effect of HePC on phosphatidylcholine biosynthesis (2a) and two examples of the use of HePC as a tool in biochemistry studies. First (2b), the regulation between both pathways of phosphatidylcholine biosynthesis, the CDP-choline pathway and via methylation of phosphatidylethanolamine. Inhibition of the CDP-choline pathway by HePC leads to an increased biosynthesis by methylation of phosphatidylethanolamine, which support the studies on a balanced synthesis of glycerolipids (for review see Tijburg et al., 1989). Second (2c), HePC antagonizes the phorbol ester-induced stimulation of phosphatidylcholine biosynthesis in Hela cells by antogonizing the increased membrane translocation of CT, which confirmed the mechanism recently suggested by Utal et al. (1991). Further targets of the use of HePC may be the sorting process of phosphoglycerides and sphingolipids, the secretion of lipoproteins or the phosphatidylcholine biosynthesis of the regenerating liver.