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探索代谢组学方法分析疟原虫磷脂生物合成途径。

Exploring metabolomic approaches to analyse phospholipid biosynthetic pathways in Plasmodium.

机构信息

Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235, Centre National de la Recherche Scientifique - UM1-UM2, Université Montpellier 2, cc 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.

出版信息

Parasitology. 2010 Aug;137(9):1343-56. doi: 10.1017/S0031182009991934. Epub 2010 Jan 29.

Abstract

SUMMARYPlasmodium falciparum, the agent responsible for malaria, is an obligate intracellular protozoan parasite. For proliferation, differentiation and survival, it relies on its own protein-encoding genes, as well as its host cells for nutrient sources. Nutrients and subsequent metabolites are required by the parasites to support their high rate of growth and replication, particularly in the intra-erythrocytic stages of the parasite that are responsible for the clinical symptoms of the disease. Advances in mass spectrometry have improved the analysis of endogenous metabolites and enabled a global approach to identify the parasite's metabolites by the so-called metabolomic analyses. This level of analysis complements the genomic, transcriptomic and proteomic data already available and should allow the identification of novel metabolites, original pathways and networks of regulatory interactions within the parasite, and between the parasite and its hosts. The field of metabolomics is just in its infancy in P. falciparum, hence in this review, we concentrate on the available methodologies and their potential applications for deciphering important biochemical processes of the parasite, such as the astonishingly diverse phospholipid biosynthesis pathways. Elucidating the regulation of the biosynthesis of these crucial metabolites could help design of future anti-malarial drugs.

摘要

总结

疟原虫是引起疟疾的病原体,是一种专性的内共生原生动物寄生虫。为了增殖、分化和生存,它依赖于自身的蛋白质编码基因以及宿主细胞的营养来源。营养物质和随后的代谢物是寄生虫生长和复制所必需的,特别是在寄生虫的红细胞内阶段,这是导致疾病临床症状的原因。质谱技术的进步提高了内源性代谢物的分析水平,并通过所谓的代谢组学分析实现了对寄生虫代谢物的全面分析方法。这种分析水平补充了现有的基因组、转录组和蛋白质组数据,应该能够识别寄生虫内部以及寄生虫与其宿主之间的新代谢物、原始途径和调控相互作用网络。代谢组学领域在疟原虫中还处于起步阶段,因此在这篇综述中,我们集中讨论了现有的方法及其在破译寄生虫重要生化过程中的潜在应用,例如令人惊讶的多样化磷脂生物合成途径。阐明这些关键代谢物生物合成的调控机制可能有助于设计未来的抗疟药物。

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