Exploring metabolomic approaches to analyse phospholipid biosynthetic pathways in Plasmodium

Exploring metabolomic approaches to analyse phospholipid biosynthetic pathways in Plasmodium
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DOI:
10.1017/s0031182009991934
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发表时间:
2010-08-01
期刊:
影响因子:
2.4
通讯作者:
Vial, H. J.
Vial, H. J.
中科院分区:
医学2区
文献类型:
--
作者:
Besteiro, S.;Duy, S. Vo;Vial, H. J.

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恶性疟原虫是引起疟疾的病原体,是一种专性细胞内原生动物寄生虫。对于增殖,分化和生存,它依赖于自己的蛋白质编码基因,以及其宿主细胞的营养来源。寄生虫需要营养物和随后的代谢物来支持它们的高生长和复制速率,特别是在寄生虫的红细胞内阶段,这是造成疾病临床症状的原因。质谱技术的进步改善了内源性代谢物的分析,并通过所谓的代谢组学分析实现了识别寄生虫代谢物的全球方法。这种水平的分析补充了基因组,转录组和蛋白质组学数据已经存在,并应允许识别新的代谢物,原始途径和网络的监管相互作用的寄生虫,寄生虫和它的主机之间。代谢组学在恶性疟原虫中的研究还处于起步阶段,因此,本文主要介绍了目前研究恶性疟原虫重要生化过程的方法及其潜在应用,如恶性疟原虫磷脂生物合成途径的多样性。阐明这些关键代谢物的生物合成调控可以帮助设计未来的抗疟疾药物。
Plasmodium 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. falciparunz, 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.