Tang Tian, Li Cang-Hai, Jiang Ting-Liang
Research Center of Artemisinin, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2018 Sep;43(18):3771-3781. doi: 10.19540/j.cnki.cjcmm.20180726.012.
Heme is a key metabolic factor in all life. Malaria parasite has de novo heme-biosynthetic pathway, however the growth and development of parasite depend on the hemoglobin-derived heme metabolism process during the intraerythrocytic stages, such as the ingestion and degradation of hemoglobin in the food vacuole. The hemoglobin metabolism in the food vesicles mainly includes four aspects: hemoglobin transport and intake, hemoglobin enzymolysis to produce heme, heme polymerization into malarial pigment, and heme transport via the food vacuole. The potential mechanisms of antimalarial drugs,such as chloroquine, artemisinin and atovaquone may be related to this process. The main four aspects of this metabolic process, key metabolic enzymes, effects of antimalarial drugs on the process and their potential mechanism of action would be summarized in this paper, providing ideas for rational use and mechanism exploration of similar drugs.
血红素是所有生命中的关键代谢因子。疟原虫具有从头合成血红素的生物合成途径,然而,在红细胞内阶段,疟原虫的生长和发育依赖于源自血红蛋白的血红素代谢过程,例如在食物泡中对血红蛋白的摄取和降解。食物泡中的血红蛋白代谢主要包括四个方面:血红蛋白的运输和摄取、血红蛋白酶解产生血红素、血红素聚合成疟色素以及血红素通过食物泡的运输。抗疟药物如氯喹、青蒿素和阿托伐醌的潜在作用机制可能与此过程有关。本文将总结这一代谢过程的主要四个方面、关键代谢酶、抗疟药物对该过程的影响及其潜在作用机制,为同类药物的合理使用和作用机制探索提供思路。