The phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells.
The influence of the phospholipid analogue hexadecylphosphocholine on phosphatidylcholine biosynthesis was investigated in Madin-Darby canine kidney (MDCK) cells. It inhibits the incorporation rate of [methyl-3H]choline into phosphatidylcholine at a concentration of 50 microM by about 50%. The radiolabelled precursor accumulates in the phosphocholine pool indicating that hexadecylphosphocholine inhibits the formation of phosphatidylcholine via the CDP-choline pathway at the level of the rate-limiting enzyme. CTP:phosphocholine cytidylyl transferase (EC 2.7.7.15). This was verified by the determination of the activity of the enzyme in vitro. In consequence of its inhibitory effect it could be shown that the treatment of MDGK cells for 24 h with 50 microM hexadecylphosphocholine induces alterations of the phospholipid composition. Whereas in treated cells the relative phosphatidylcholine content was decreased from the control level of 36.0 +/- 0.9% to 29.9 +/- 0.2%; in contrast, the relative content of phosphatidylethanolamine was increased from 19.3 +/- 0.9% to 24.3 +/- 0.9%.
Haase
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R
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Germany.
Wieder
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T
Geilen
C C
CC
Reutter
W
W
D000818:Animals; D002460:Cell Line; D002794:Choline / Q000032:analysis; D004285:Dogs; D007700:Kinetics; D000216:N-Acylneuraminate Cytidylyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000032:analysis / Q000096:biosynthesis*; D010714:Phosphatidylethanolamines / Q000032:analysis; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010767:Phosphorylcholine; C039128:miltefosine; D000216:N-Acylneuraminate Cytidylyltransferase; D002794:Choline