Pandey A V, Tekwani B L
Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
FEBS Lett. 1997 Feb 3;402(2-3):236-40. doi: 10.1016/s0014-5793(96)01536-0.
Malaria parasite digests hemoglobin and utilizes the globin part for its nutritional requirements. Heme released as a byproduct of hemoglobin degradation is detoxified by polymerization into a crystalline, insoluble pigment, known as hemozoin. We have identified a novel reaction of depolymerization of hemozoin to heme. This reaction is initiated by the interaction of blood schizonticidal antimalarial drugs with the malarial hemozoin. The reaction has been confirmed, with the purified hemozoin as well as the lysate of the malaria parasite. Pigment breakdown was studied by infrared spectroscopy, thin-layer chromatography and spectrophotometric analysis. It was complete within 2 h of drug exposure, which explains the selective sensitivity of late stages (trophozoites and schizonts) of malarial parasites loaded with the hemozoin pigment to the toxic action of these drugs. It is suggested that the failure of the parasite heme detoxification system due to this reaction results in the accumulation of toxic heme, which alone, or complexed with the antimalarial leads to the death of malaria parasite.
疟原虫消化血红蛋白，并利用珠蛋白部分满足其营养需求。作为血红蛋白降解副产物释放的血红素通过聚合成一种结晶性、不溶性色素（即疟色素）而被解毒。我们发现了疟色素解聚为血红素的新反应。该反应由血液裂殖体杀灭性抗疟药物与疟原虫疟色素的相互作用引发。该反应已通过纯化的疟色素以及疟原虫裂解物得到证实。通过红外光谱、薄层色谱和分光光度分析研究了色素分解情况。药物暴露后2小时内分解完成，这解释了富含疟色素的疟原虫晚期（滋养体和裂殖体）对这些药物毒性作用的选择性敏感性。有人认为，由于该反应导致寄生虫血红素解毒系统失效，从而导致有毒血红素积累，其单独存在或与抗疟药物结合都会导致疟原虫死亡。
