Phospholipid analogues: side chain- and polar head group-dependent effects on phosphatidylcholine biosynthesis.
In recent studies we showed that the phospholipid analogue hexadecylphosphocholine inhibits phosphatidylcholine biosynthesis by affecting the translocation of the rate-limiting enzyme of phosphatidylcholine biosynthesis, CTP:phosphocholine cytidylyltransferase (EC 2.7.7.15), to membranes, where it is active (Geilen et al. 1992. J. Biol. Chem. 267: 6719-6724). The present study was performed to investigate the structure-dependency of this effect. It is shown that the inhibitory properties of phospholipid analogues are dependent on their alkyl side chain length (dodecylphosphocholine < tetradecylphosphocholine < hexadecylphosphocholine < heptadecylphosphocholine < octadecylphosphocholine > eicosadecylphosphocholine). Furthermore, it is demonstrated that this inhibition of phosphatidylcholine biosynthesis by phospholipid analogues is also dependent on the polar head group (hexadecylphosphocholine >> hexadecylphosphoethanolamine = hexadecylphosphoserine). These effects result from an inhibition of the CTP:phosphocholine cytidylyltransferase and are not due to an inhibition of choline uptake or differences in the cellular uptake of the phospholipid analogues investigated.
Geilen
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CC
Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, Germany.
Haase
A
A
Wieder
T
T
Arndt
D
D
Zeisig
R
R
Reutter
W
W
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase; D004072:Digitonin / Q000494:pharmacology; D004285:Dogs; D007668:Kidney / Q000166:cytology; D009713:Nucleotidyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010713:Phosphatidylcholines; D010743:Phospholipids; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D004072:Digitonin; D013755:Tetradecanoylphorbol Acetate