MALARIAL HAEMOZOIN BETA-HEMATIN SUPPORTS HEME POLYMERIZATION IN THE ABSENCE OF PROTEIN
MALARIAL HAEMOZOIN BETA-HEMATIN SUPPORTS HEME POLYMERIZATION IN THE ABSENCE OF PROTEIN
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DOI：
10.1038/374269a0
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发表时间：
1995-03-16
期刊：
影响因子：
64.8
通讯作者：
RIDLEY, RG
中科院分区：
文献类型：
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作者：
DORN, A;STOFFEL, R;RIDLEY, RG
在红细胞内生长的疟疾寄生虫在溶酶体细胞器消化泡内消化宿主细胞高达80%的血红蛋白（1，2）。它们将在此过程中释放的潜在毒性血红素（Fe（II）原血卟啉）隔离为一种称为疟原虫色素的不溶性色素，该色素由聚合的Fe（III）原血卟啉亚基组成（3）。我们已经研究了血红素聚合的这个过程，以前报道这是酶介导的，也是喹啉类抗疟药氯喹和奎宁的靶点（4）。在这里，我们表明，而不是酶介导的，血红素聚合实际上是一个化学过程，只依赖于存在的血红素衍生材料与疟原虫色素，而不是蛋白质。这一发现并没有使血红素聚合作为药物干预的靶点失效，并且引发疟原虫色素形成的机制仍然不清楚，但我们对这一过程和氯喹作用的看法必须重新考虑。
MALARIAL parasites growing inside erythrocytes digest up to 80% of the host cell's haemoglobin within a lysosomal organelle, the digestive vacuole(1,2). They sequester the potentially toxic haem (Fe (II) protohaematoporphyrin) that is released during this process into an insoluble pigment called haemozoin, which consists of polymerized Fe(III) protohaematoporphyrin subunits(3). We have studied this process of haem polymerization, which was previously reported to be enzyme-mediated and the target of the quinoline antimalarial drugs chloroquine and quinine(4). Here we show that, rather than being enzyme-mediated, haem polymerization is actually a chemical process, dependent only on the presence of haem-derived material associated with haemozoin and not on protein. This discovery does not invalidate haem polymerization as a target for drug intervention and the mechanism by which haemozoin formation is initiated is still not understood, but our view of this process and of the action of chloroquine must be reconsidered.