Biosynthesis of GDP-fucose and other sugar nucleotides in the blood stages of Plasmodium falciparum.
Biosynthesis of GDP-fucose and other sugar nucleotides in the blood stages of Plasmodium falciparum.
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恶性疟原虫血液阶段 GDP-岩藻糖和其他糖核苷酸的生物合成。
DOI：
10.1074/jbc.m112.439828
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Izquierdo,Luis
中科院分区：
文献类型：
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作者：
Sanz,Sílvia;Bandini,Giulia;Ospina,Diego;Bernabeu,Maria;Mariño,Karina;Fernández-Becerra,Carmen;Izquierdo,Luis
碳水化合物结构在许多生物过程中起着重要作用，包括细胞粘附、细胞间通讯和宿主-病原体相互作用。糖核苷酸是被细胞用作大多数糖基化反应的供体的糖的活化形式。采用液相色谱-串联质谱法，对恶性疟原虫红内期各阶段的UDP-葡萄糖、UDP-半乳糖、UDP-N-乙酰氨基葡萄糖、GDP-甘露糖和GDP-岩藻糖进行了鉴定和定量。我们将这些数据与从P. falciparumannotated基因组，揭示了新的活性生物合成途径的关键进一步糖基化反应。岩藻糖是存在于糖缀合物中的糖，通常与识别和粘附事件相关。因此，GDP-岩藻糖前体在多种生物体中是必需的。恶性疟原虫存在体外活化的GDP-甘露糖4，6-脱氢酶和GDP-1-岩藻糖合成酶的同源物，表明大多数GDP-岩藻糖是通过涉及GDP-甘露糖生物转化的新途径形成的。与岩藻糖补救途径有关的酶的同源物在P.恶性疟原虫基因组这与体内代谢标记实验一致，表明寄生虫未显著掺入岩藻糖。荧光显微镜下的表位标记的版本的P。在转基因3D 7寄生虫中表达的GDP-甘露糖4，6-脱氢酶和GDP-1-岩藻糖合成酶表明，这些酶定位于恶性疟原虫的细胞质中。恶性疟原虫在红细胞内发育周期。虽然岩藻糖在寄生虫中的功能尚不清楚，但GDP-岩藻糖的存在表明其代谢产物可用于进一步的岩藻糖基化反应。falciparumgenome.Results:这些途径是活跃在红细胞内的生活cycle的parasit.Conclusion：寄生虫生物合成GDP岩藻糖和其他糖核苷酸不相关的糖基磷脂酰肌醇structuresSignificance：他们的存在强烈表明，他们参与的聚糖的生物合成尚未确定。
Carbohydrate structures play important roles in many biological processes, including cell adhesion, cell-cell communication, and host-pathogen interactions. Sugar nucleotides are activated forms of sugars used by the cell as donors for most glycosylation reactions. Using a liquid chromatography-tandem mass spectrometry-based method, we identified and quantified the pools of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, GDP-mannose, and GDP-fucose inPlasmodium falciparumintraerythrocytic life stages. We assembled these data with thein silicofunctional reconstruction of the parasite metabolic pathways obtained from theP. falciparumannotated genome, exposing new active biosynthetic routes crucial for further glycosylation reactions. Fucose is a sugar present in glycoconjugates often associated with recognition and adhesion events. Thus, the GDP-fucose precursor is essential in a wide variety of organisms.P. falciparumpresents homologues of GDP-mannose 4,6-dehydratase and GDP-l-fucose synthase enzymes that are activein vitro, indicating that most GDP-fucose is formed by ade novopathway that involves the bioconversion of GDP-mannose. Homologues for enzymes involved in a fucose salvage pathway are apparently absent in theP. falciparumgenome. This is in agreement within vivometabolic labeling experiments showing that fucose is not significantly incorporated by the parasite. Fluorescence microscopy of epitope-tagged versions ofP. falciparumGDP-mannose 4,6-dehydratase and GDP-l-fucose synthase expressed in transgenic 3D7 parasites shows that these enzymes localize in the cytoplasm ofP. falciparumduring the intraerythrocytic developmental cycle. Although the function of fucose in the parasite is not known, the presence of GDP-fucose suggests that the metabolite may be used for further fucosylation reactions.Background: GDP-fucose and other sugar nucleotide biosynthetic pathways are conserved in theP. falciparumgenome.Results: These pathways are active in the intraerythrocytic life cycle of the parasite.Conclusion: The parasite biosynthesizes GDP-fucose and other sugar nucleotides not related to the glycosylphosphatidylinositol structuresSignificance: Their presence strongly suggests that they are involved in the biosynthesis of glycans not yet characterized.