Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas 77204, USA.
J Chem Phys. 2013 Sep 28;139(12):121911. doi: 10.1063/1.4816106.
Hematin crystallization is the main mechanism of detoxification of heme that is released in malaria-infected erythrocytes as a byproduct of the hemoglobin catabolism by the parasite. A controversy exists over whether hematin crystals grow from the aqueous medium of the parasite's digestive vacuole or in the lipid bodies present in the vacuole. To this end, we compare the basic thermodynamic and structural features of hematin crystallization in an aqueous buffer at pH 4.8, as in the digestive vacuole, and in water-saturated octanol that mimics the environment of the lipid nanospheres. We show that in aqueous solutions, hematin aggregation into mesoscopic disordered clusters is insignificant. We determine the solubility of the β-hematin crystals in the pH range 4.8-7.6. We image by atomic force microscopy crystals grown at pH 4.8 and show that their macroscopic and mesoscopic morphology features are incompatible with those reported for biological hemozoin. In contrast, crystals grown in the presence of octanol are very similar to those extracted from parasites. We determine the hematin solubility in water-saturated octanol at three temperatures. These solubilities are four orders of magnitude higher than that at pH 4.8, providing for faster crystallization from organic than from aqueous solvents. These observations further suggest that the lipid bodies play a role in mediating biological hemozoin crystal growth to ensure faster heme detoxification.
血红素结晶是疟原虫代谢血红蛋白产生的血红素的主要解毒机制，血红素会从感染疟原虫的红细胞中释放出来。血红素结晶是在寄生虫的消化液泡中的水溶液中生长，还是在液泡中存在的脂质体中生长，这一问题存在争议。为此，我们比较了在 pH 值为 4.8 的水性缓冲液（类似于消化液泡中的环境）中和在水饱和辛醇中（模拟脂质纳米球的环境）血红素结晶的基本热力学和结构特征。我们表明，在水性溶液中，血红素聚集成介观无序簇的聚集作用并不显著。我们确定了β-血红素晶体在 pH 值 4.8-7.6 范围内的溶解度。我们通过原子力显微镜对在 pH 值为 4.8 下生长的晶体进行成像，并表明其宏观和介观形态特征与生物血红素报告的特征不兼容。相比之下，在辛醇存在下生长的晶体与从寄生虫中提取的晶体非常相似。我们在三个温度下确定了水饱和辛醇中的血红素溶解度。这些溶解度比在 pH 值为 4.8 时高四个数量级，这表明从有机溶剂中比从水性溶剂中更快地结晶。这些观察结果进一步表明，脂质体在介导生物血红素晶体生长以确保更快地解毒血红素方面发挥作用。
