Lack of heme synthesis in a free-living eukaryote
Lack of heme synthesis in a free-living eukaryote
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DOI：
10.1073/pnas.0500877102
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发表时间：
2005-03-22
影响因子：
11.1
通讯作者：
Hamza, I
中科院分区：
文献类型：
--
作者：
Rao, AU;Carta, LK;Hamza, I
在迄今为止研究的大多数自由生活的真核生物中，血红素是通过一个定义明确的进化保守途径由一系列中间体合成的。我们发现，自由生活的蠕虫，包括模式遗传生物秀丽隐杆线虫，和寄生蠕虫是无法合成血红素从头，即使这些动物含有血红素蛋白，在关键的生物过程中发挥作用。放射性同位素，荧光标记，血红素类似物的研究表明，线虫收购血红素从外源性来源。铁剥夺蠕虫无法生长在存在足够的血红素，除非获救增加血红素水平的生长培养基。这些数据表明，虽然蠕虫使用膳食血红素纳入血红素蛋白，摄入血红素也被用作铁源时，铁是有限的。我们的研究结果提供了一个生化基础的依赖蠕虫的生长和发育的血红素，他们建议，在蠕虫的血红素转运途径的药理靶向可能是一个重要的控制措施蠕虫感染。
In most free-living eukaryotes studied thus far, heme is synthesized from a series of intermediates through a well defined evolutionarily conserved pathway. We found that free-living worms, including the model genetic organism Caenorhabditis elegans, and parasitic helminths are unable to synthesize heme de novo, even though these animals contain hemoproteins that function in key biological processes. Radioisotope, fluorescence labeling, and heme analog studies suggest that C elegans acquires heme from exogenous sources. Iron-deprived worms were unable to grow in the presence of adequate heme unless rescued by increasing heme levels in the growth medium. These data indicate that although worms use dietary heme for incorporation into hemoproteins, ingested heme is also used as an iron source when iron is limiting. Our results provide a biochemical basis for the dependence of worm growth and development on heme, and they suggest that pharmacologic targeting of heme transport pathways in worms could be an important control measure for helminthic infections.