Purine salvage in Leishmania: complex or simple by design?

Purine salvage in Leishmania: complex or simple by design?
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DOI:
10.1016/j.pt.2012.05.005
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发表时间:
2012-08
影响因子:
9.6
通讯作者:
Carter NS
Carter NS
中科院分区:
医学1区
文献类型:
--
作者:
Boitz JM;Ullman B;Jardim A;Carter NS

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嘌呤核苷酸在多种重要的细胞和代谢过程中起作用,包括能量产生、细胞信号传导、维生素衍生的辅因子和核酸的合成,以及作为细胞命运的决定因素。与它们的哺乳动物和昆虫宿主不同,利什曼原虫不能重新合成嘌呤环,并且绝对依赖它们来满足它们的嘌呤需求。因此,这些寄生虫中嘌呤补救的强制性性质为药物靶向提供了一个有吸引力的范例,因此,该途径的描述已经进行了30多年的科学研究。在这里,我们回顾了最近的事态发展,揭示了如何嘌呤通量在利什曼原虫,并提供了一个潜在的“阿喀琉斯之踵”,为未来的验证。
Purine nucleotides function in a variety of vital cellular and metabolic processes including energy production, cell signaling, synthesis of vitamin-derived cofactors and nucleic acids, and as determinants of cell fate. Unlike their mammalian and insect hosts, Leishmania cannot synthesize the purine ring de novo and are absolutely dependent upon them to meet their purine requirements. The obligatory nature of purine salvage in these parasites, therefore, offers an attractive paradigm for drug targeting, and consequently, the delineation of the pathway has been under scientific investigation for over 30 years. Here we review recent developments that reveal how purines flux in Leishmania and offer a potential ‘Achilles’ heel’ for future validation.
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发表时间: 2007-03-01
影响因子: 1.5
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