title: Phospholipid analogues: side chain- and polar head group-dependent effects on phosphatidylcholine biosynthesis.
abstract: 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.
authors.affiliation: Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, Germany.
authors.forename: C C
authors.initials: CC
authors.lastname: Geilen
authors.forename: A
authors.initials: A
authors.lastname: Haase
authors.forename: T
authors.initials: T
authors.lastname: Wieder
authors.forename: D
authors.initials: D
authors.lastname: Arndt
authors.forename: R
authors.initials: R
authors.lastname: Zeisig
authors.forename: W
authors.initials: W
authors.lastname: Reutter
mesh_terms: 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
chemical_list: D010713:Phosphatidylcholines; D010743:Phospholipids; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D004072:Digitonin; D013755:Tetradecanoylphorbol Acetate