Nzila Alexis, Ward Steve A, Marsh Kevin, Sims Paul F G, Hyde John E
Kenya Medical Research Institute and Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, PO Box 43640, Nairobi GPO 00100, Kenya.
Trends Parasitol. 2005 Jul;21(7):334-9. doi: 10.1016/j.pt.2005.05.008.
The folate pathway represents a powerful target for combating rapidly dividing systems such as cancer cells, bacteria and malaria parasites. Whereas folate metabolism in mammalian cells and bacteria has been studied extensively, it is understood less well in malaria parasites. In two articles, we attempt to reconstitute the malaria folate pathway based on available information from mammalian and microbial systems, in addition to Plasmodium-genome-sequencing projects. In part I, we focused on folate enzymes that are already used clinically as anticancer drug targets or that are under development in drug-discovery programs. In this article, we discuss mammalian folate enzymes that have not yet been exploited as potential drug targets, and enzymes that function in the de novo folate-synthesis pathway of the parasite--a particularly attractive area of attack because of its absence from the mammalian host.
叶酸途径是对抗癌细胞、细菌和疟原虫等快速分裂系统的有力靶点。虽然哺乳动物细胞和细菌中的叶酸代谢已得到广泛研究，但对疟原虫叶酸代谢的了解却较少。在两篇文章中，我们除了依据疟原虫基因组测序项目所获得的信息外，还尝试根据来自哺乳动物和微生物系统的现有信息来重建疟原虫叶酸途径。在第一部分，我们重点关注了那些已在临床上用作抗癌药物靶点或正处于药物研发项目中的叶酸酶。在本文中，我们将讨论尚未被开发为潜在药物靶点的哺乳动物叶酸酶，以及在疟原虫从头合成叶酸途径中发挥作用的酶——由于哺乳动物宿主中不存在该途径，这是一个特别有吸引力的攻击领域。
