Macêdo Juan P, Schmidt Remo S, Mäser Pascal, Rentsch Doris, Vial Henri J, Sigel Erwin, Bütikofer Peter
Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
Mol Biochem Parasitol. 2013 Jul;190(1):16-22. doi: 10.1016/j.molbiopara.2013.05.007. Epub 2013 Jun 6.
Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synthesis of choline-containing phospholipids, such as phosphatidylcholine (PC). According to published data, Trypanosoma brucei parasites are unable to take up choline from the environment but instead use lyso-phosphatidylcholine as precursor for choline lipid synthesis. We now show that T. brucei procyclic forms in culture readily incorporate [(3)H]-labeled choline into PC, indicating that trypanosomes express a transporter for choline at the plasma membrane. Characterization of the transport system in T. brucei procyclic and bloodstream forms shows that uptake of choline is independent of sodium and potassium ions and occurs with a Km in the low micromolar range. In addition, we demonstrate that choline uptake can be blocked by the known choline transport inhibitor, hemicholinium-3, and by synthetic choline analogs that have been established as anti-malarials. Together, our results show that T. brucei parasites express an uptake system for choline and that exogenous choline is used for PC synthesis.
胆碱是真核细胞的一种必需营养素，在真核细胞中它被用作合成含胆碱磷脂（如磷脂酰胆碱，PC）的前体。根据已发表的数据，布氏锥虫寄生虫无法从环境中摄取胆碱，而是利用溶血磷脂酰胆碱作为胆碱脂质合成的前体。我们现在表明，培养中的布氏锥虫前循环型能够轻易地将[³H]标记的胆碱掺入PC中，这表明锥虫在质膜上表达一种胆碱转运体。对布氏锥虫前循环型和血流型中转运系统的特性分析表明，胆碱的摄取不依赖于钠离子和钾离子，其米氏常数（Km）处于低微摩尔范围。此外，我们证明胆碱摄取可被已知的胆碱转运抑制剂3-羟甲基胆碱以及已被确立为抗疟药物的合成胆碱类似物所阻断。总之，我们的结果表明布氏锥虫寄生虫表达一种胆碱摄取系统，并且外源性胆碱用于PC合成。
