Department of Biochemistry and Molecular Biology, University of Melbourne, 30 Flemington Rd, Parkville, 3010, Victoria, Australia.
Parasitology. 2010 Aug;137(9):1303-13. doi: 10.1017/S0031182010000077. Epub 2010 Feb 17.
Leishmania spp. are sandfly-transmitted protozoa parasites that cause a spectrum of diseases in humans. Many enzymes involved in Leishmania central carbon metabolism differ from their equivalents in the mammalian host and are potential drug targets. In this review we summarize recent advances in our understanding of Leishmania central carbon metabolism, focusing on pathways of carbon utilization that are required for growth and pathogenesis in the mammalian host. While Leishmania central carbon metabolism shares many features in common with other pathogenic trypanosomatids, significant differences are also apparent. Leishmania parasites are also unusual in constitutively expressing most core metabolic pathways throughout their life cycle, a feature that may allow these parasites to exploit a range of different carbon sources (primarily sugars and amino acids) rapidly in both the insect vector and vertebrate host. Indeed, recent gene deletion studies suggest that mammal-infective stages are dependent on multiple carbon sources in vivo. The application of metabolomic approaches, outlined here, are likely to be important in defining aspects of central carbon metabolism that are essential at different stages of mammalian host infection.
利什曼原虫属是通过沙蝇传播的原生动物寄生虫,可引起人类一系列疾病。许多参与利什曼原虫中心碳代谢的酶与哺乳动物宿主中的等效酶不同,是潜在的药物靶点。在这篇综述中,我们总结了对利什曼原虫中心碳代谢的最新认识,重点介绍了在哺乳动物宿主中生长和发病所必需的碳利用途径。虽然利什曼原虫中心碳代谢与其他致病性锥虫有许多共同特征,但也存在明显差异。利什曼原虫寄生虫在整个生命周期中还持续表达大多数核心代谢途径,这一特征可能使这些寄生虫能够在昆虫媒介和脊椎动物宿主中迅速利用多种不同的碳源(主要是糖和氨基酸)。事实上,最近的基因缺失研究表明,感染哺乳动物的阶段在体内依赖多种碳源。这里概述的代谢组学方法的应用,可能对确定哺乳动物宿主感染不同阶段的中心碳代谢的重要方面具有重要意义。