肌醇摄取对于布鲁氏锥虫中肌醇磷脂的大量合成是必需的，但对糖基磷脂酰肌醇的合成不是必需的。
myo-Inositol uptake is essential for bulk inositol phospholipid but not glycosylphosphatidylinositol synthesis in Trypanosoma brucei.
机构信息
Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
出版信息
J Biol Chem. 2012 Apr 13;287(16):13313-23. doi: 10.1074/jbc.M112.344812. Epub 2012 Feb 20.
Abstract
myo-Inositol is an essential precursor for the production of inositol phosphates and inositol phospholipids in all eukaryotes. Intracellular myo-inositol is generated by de novo synthesis from glucose 6-phosphate or is provided from the environment via myo-inositol symporters. We show that in Trypanosoma brucei, the causative pathogen of human African sleeping sickness and nagana in domestic animals, myo-inositol is taken up via a specific proton-coupled electrogenic symport and that this transport is essential for parasite survival in culture. Down-regulation of the myo-inositol transporter using RNA interference inhibited uptake of myo-inositol and blocked the synthesis of the myo-inositol-containing phospholipids, phosphatidylinositol and inositol phosphorylceramide; in contrast, it had no effect on glycosylphosphatidylinositol production. This together with the unexpected localization of the myo-inositol transporter in both the plasma membrane and the Golgi demonstrate that metabolism of endogenous and exogenous myo-inositol in T. brucei is strictly segregated.
摘要
肌醇是所有真核生物中肌醇磷酸盐和肌醇磷脂合成的必需前体。细胞内肌醇由葡萄糖 6-磷酸从头合成产生，或者通过肌醇转运蛋白从环境中提供。我们表明，在引起人类昏睡病和家畜纳格纳病的病原体布氏锥虫中，肌醇通过特定的质子偶联的电致运动来摄取，并且这种运输对寄生虫在培养中的存活是必需的。使用 RNA 干扰下调肌醇转运蛋白的表达会抑制肌醇的摄取并阻断肌醇磷脂（磷脂酰肌醇和肌醇磷酸神经酰胺）的合成；相比之下，它对糖基磷脂酰肌醇的产生没有影响。这与肌醇转运蛋白在质膜和高尔基体中的意外定位一起表明，布氏锥虫内源性和外源性肌醇的代谢是严格分隔的。
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