Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum
Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum
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DOI：
10.1074/jbc.273.17.10190
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发表时间：
1998-04-24
影响因子：
4.8
通讯作者：
Kirk, K
中科院分区：
文献类型：
--
作者：
Saliba, KJ;Horner, HA;Kirk, K
人类疟疾寄生虫恶性疟原虫在其宿主红细胞内的生长依赖于从细胞外培养基中摄取一些必需营养素。其中之一是泛酸，这是一种水溶性维生素，是辅酶a的前体。在本研究中，我们发现正常未感染的红细胞对泛酸是不渗透的，但这种维生素通过一种转运途径被迅速吸收到疟疾感染的细胞中，这种转运途径具有先前表征的特征（速尿敏感性、不饱和性），这种转运途径是由宿主细胞膜内的细胞内寄生虫诱导的，具有广泛的特异性渗透途径。因此，泛酸盐的运输对这些途径具有重要的生理作用。在被寄生的细胞内，泛酸盐经历磷酸化，这是其转化为辅酶a的第一步。在皂素渗透红细胞内的寄生虫被证明摄取泛酸盐并使其磷酸化，这与细胞内寄生虫同时具有泛酸转运体和泛酸激酶一致。从未感染和感染的红细胞中制备的裂解物对泛酸盐磷酸化率的比较表明，恶性疟原虫滋养体的泛酸激酶活性比其宿主细胞的泛酸激酶活性高约10倍，并且疟疾感染细胞中泛酸盐的大部分磷酸化（如果不是全部的话）发生在细胞内寄生虫中。这些结果与先前的研究结果相反，先前的研究提出禽疟原虫lophurae缺乏泛酸激酶（以及其他合成辅酶A的酶），并且依赖于从宿主细胞细胞质中摄取预形成的辅酶A。
The growth of the human malaria parasite, Plasmodium falciparum, within its host erythrocyte is reliant on the uptake of a number of essential nutrients from the extracellular medium. One of these is pantothenic acid, a water-soluble vitamin that is a precursor of coenzyme A. In this study we show that normal uninfected erythrocytes are impermeable to pantothenate but that the vitamin is taken up rapidly into malaria-infected cells via a transport pathway that has the characteristics (furosemide sensitivity, nonsaturability) of previously characterized, broad specificity permeation pathways induced by the intracellular parasite in the host cell membrane. The transport of pantothenate therefore constitutes a critical physiological role for these pathways. Inside the parasitized cell pantothenate undergoes phosphorylation, the first step in its conversion to coenzyme A. Parasites within saponin-permeabilized erythrocytes were shown to take up and phosphorylate pantothenate, consistent with the intracellular parasite having both a pantothenate transporter and a pantothenate kinase, Comparisons of the rate of phosphorylation of pantothenate by lysates prepared from uninfected and infected erythrocytes revealed that the pantothenate kinase activity of the P., falciparum trophozoite is some 10-fold higher than that of its host cell and that most, if not all, of the phosphorylation of pantothenate within the malaria-infected cell occurs within the intracellular parasite. These results contrast with those of previous studies in which it was proposed that the avian malaria parasite Plasmodium lophurae lacks pantothenate kinase (as well as the other enzymes for the synthesis of coenzyme A) and is reliant upon the uptake of preformed coenzyme A from the host cell cytosol.