Martin Rowena E, Kirk Kiaran
School of Biochemistry and Molecular Biology, The Australian National University, Canberra, Australia.
Blood. 2007 Mar 1;109(5):2217-24. doi: 10.1182/blood-2005-11-026963. Epub 2006 Oct 17.
The intraerythrocytic malaria parasite derives much of its requirement for amino acids from the digestion of the hemoglobin of its host cell. However, one amino acid, isoleucine, is absent from adult human hemoglobin and must therefore be obtained from the extracellular medium. In this study we have characterized the mechanisms involved in the uptake of isoleucine by the intraerythrocytic parasite. Under physiologic conditions the rate of transport of isoleucine into human erythrocytes infected with mature trophozoite-stage Plasmodium falciparum parasites is increased to approximately 5-fold that in uninfected cells, with the increased flux being via the new permeability pathways (NPPs) induced by the parasite in the host cell membrane. Transport via the NPPs ensures that protein synthesis is not rate limited by the flux of isoleucine across the erythrocyte membrane. On entering the infected erythrocyte, isoleucine is taken up into the parasite via a saturable, ATP-, Na+-, and H+-independent system which has the capacity to mediate the influx of isoleucine in exchange for leucine (liberated from hemoglobin). The accumulation of radiolabeled isoleucine within the parasite is mediated by a second (high-affinity, ATP-dependent) mechanism, perhaps involving metabolism and/or the concentration of isoleucine within an intracellular organelle.
红细胞内的疟原虫对氨基酸的许多需求都来自于其对宿主细胞血红蛋白的消化。然而，有一种氨基酸，异亮氨酸，在成人血红蛋白中并不存在，因此必须从细胞外介质中获取。在本研究中，我们已经确定了红细胞内疟原虫摄取异亮氨酸所涉及的机制。在生理条件下，异亮氨酸进入感染了成熟滋养体阶段恶性疟原虫的人类红细胞的运输速率增加到未感染细胞的约5倍，通量增加是通过寄生虫在宿主细胞膜中诱导的新通透性途径（NPPs）实现的。通过NPPs的运输确保了蛋白质合成不受异亮氨酸穿过红细胞膜通量的限制。进入被感染的红细胞后，异亮氨酸通过一个可饱和的、不依赖ATP、Na +和H +的系统被摄取到疟原虫中，该系统有能力介导异亮氨酸的流入以交换亮氨酸（从血红蛋白中释放出来）。放射性标记的异亮氨酸在疟原虫内的积累是由第二种（高亲和力、依赖ATP）机制介导的，可能涉及代谢和/或细胞内细胞器中异亮氨酸的浓缩。
