Bioavailable iron and heme metabolism in Plasmodium falciparum.
Bioavailable iron and heme metabolism in Plasmodium falciparum.
复制标题
恶性疟原虫中的生物可利用铁和血红素代谢。
DOI：
10.1007/3-540-29088-5_12
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发表时间：
2005
影响因子：
--
通讯作者：
Sullivan,DJ
中科院分区：
文献类型：
--
作者：
Scholl,PF;Tripathi,AK;Sullivan,DJ
铁代谢对于细胞功能至关重要，并且具有潜在毒性，因为铁可以催化氧自由基的产生。疟疾引起的贫血和缺铁性贫血在发展中国家都是可治疗的疾病。从绝对量来看，超过 95% 的疟原虫金属生物化学发生在酸性消化液泡中，其中血红蛋白分解代谢释放的血红素形成血红素晶体。抗疟喹啉会干扰结晶。尽管疟原虫基因组已完成，但哺乳动物或酵母细胞中描述的金属途径的成分中仍存在许多“基因缺口”。目前的证据表明，寄生虫的生物可利用铁源自不稳定的红细胞胞质池，而不是丰富的血红素铁。事实上，寄生虫必须在两个独立的细胞器（线粒体和顶端复合体）内制造自己的血红素。矛盾的是，尽管红细胞内含有丰富的铁，但铁螯合剂对疟原虫寄生虫具有杀细胞作用。疟原虫色素已成为激光解吸质谱法检测小鼠和人类疟原虫感染的敏感生物标志物。
Iron metabolism is essential for cell function and potentially toxic because iron can catalyze oxygen radical production. Malaria-attributable anemia and iron deficiency anemia coincide as being treatable diseases in the developing world. In absolute amounts, more than 95% ofPlasmodiummetal biochemistry occurs in the acidic digestive vacuole where heme released from hemoglobin catabolism forms heme crystals. The antimalarial quinolines interfere with crystallization. Despite the completion of thePlasmodiumgenome, many ‘gene gaps’ exist in components of the metal pathways described in mammalian or yeast cells. Present evidence suggests that parasite bioavailable iron originates from a labile erythrocyte cytosolic pool rather than from abundant heme iron. Indeed the parasite has to make its own heme within two separate organelles, the mitochondrion and the apicomplast. Paradoxically, despite the abundance of iron within the erythrocyte, iron chelators are cytocidal to thePlasmodiumparasite. Hemozoin has become a sensitive biomarker for laser desorption mass spectrometry detection ofPlasmodiuminfection in both mice and humans.