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疟原虫的血红素代谢是一个主要的抗疟靶点。

Heme metabolism of Plasmodium is a major antimalarial target.

作者信息

Padmanaban G, Rangarajan P N

机构信息

Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.

出版信息

Biochem Biophys Res Commun. 2000 Feb 24;268(3):665-8. doi: 10.1006/bbrc.1999.1892.

Abstract

The malarial parasite manifests unique features of heme metabolism. In the intraerythrocyte stage it utilizes the host hemoglobin to generate amino acids for its own protein synthesis, but polymerizes the acquired heme as a mechanism for detoxification. At the same time the parasite synthesizes heme de novo for metabolic use. The heme biosynthetic pathway of the parasite is similar to that of hepatocytes and erythrocytes. However, while the parasite makes its own delta-aminolevulinate (ALA) synthase that is immunochemically different from that of the host, it imports ALA dehydrase and perhaps the subsequent enzymes of the pathway from the host red cell. Many schizonticidal drugs such as chloroquine and artemisinin act by interfering with the heme metabolism of the parasite and there is scope to design new molecules based on the unique features of this metabolic machinery in the parasite.

摘要

疟原虫表现出独特的血红素代谢特征。在红细胞内期,它利用宿主血红蛋白生成氨基酸用于自身蛋白质合成,但将获取的血红素聚合作为一种解毒机制。同时,疟原虫从头合成血红素以供代谢使用。疟原虫的血红素生物合成途径与肝细胞和红细胞的相似。然而,尽管疟原虫自身制造的δ-氨基乙酰丙酸(ALA)合酶在免疫化学上与宿主的不同,但它从宿主红细胞中导入ALA脱水酶以及该途径后续的酶。许多杀裂殖体药物,如氯喹和青蒿素,通过干扰疟原虫的血红素代谢发挥作用,基于疟原虫这种代谢机制的独特特征设计新分子仍有空间。

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