Geilen C C, Haase A, Wieder T, Arndt D, Zeisig R, Reutter W
Institut für Molekularbiologie und Biochemie der Freien Universität Berlin, Germany.
J Lipid Res. 1994 Apr;35(4):625-32.
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.
在最近的研究中，我们发现磷脂类似物十六烷基磷胆碱通过影响磷脂酰胆碱生物合成的限速酶CTP：磷酸胆碱胞苷转移酶（EC 2.7.7.15）向其发挥活性的膜的转位，从而抑制磷脂酰胆碱的生物合成（Geilen等人，1992年。《生物化学杂志》267：6719 - 6724）。本研究旨在探究这种效应的结构依赖性。结果表明，磷脂类似物的抑制特性取决于其烷基侧链长度（十二烷基磷胆碱＜十四烷基磷胆碱＜十六烷基磷胆碱＜十七烷基磷胆碱＜十八烷基磷胆碱＞二十碳烷基磷胆碱）。此外，还证明了磷脂类似物对磷脂酰胆碱生物合成的这种抑制作用也取决于极性头部基团（十六烷基磷胆碱＞＞十六烷基磷乙醇胺 = 十六烷基磷丝氨酸）。这些效应是由CTP：磷酸胆碱胞苷转移酶的抑制引起的，而非由于胆碱摄取的抑制或所研究的磷脂类似物细胞摄取的差异。
