Effects of Amino Acids on Malarial Heme Crystallization

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  • Uyen Dinh Thanh
    Department of Applied Biology, Kyoto Institute of Technology
  • Huy Nguyen Tien
    Department of Applied Biology, Kyoto Institute of Technology Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University
  • Trang Dai Thi Xuan
    Department of Applied Biology, Kyoto Institute of Technology
  • Nhien Nguyen Thanh Thuy
    Department of Applied Biology, Kyoto Institute of Technology
  • Oida Tatsuo
    Department of Materials and Science, Kyoto Institute of Technology
  • Hirayama Kenji
    Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University
  • Harada Shigeharu
    Department of Applied Biology, Kyoto Institute of Technology
  • Kamei Kaeko
    Department of Applied Biology, Kyoto Institute of Technology

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To gain insight into the mechanism of malarial hemozoin formation and to explore various biological groups for screening novel antimalarial drugs, we examined the effects of amino acids on the formation of β-hematin (BH), which is a synthetic heme crystal structurally identical to hemozoin, in vitro. Our results showed that BH formation was significantly inhibited by basic amino acids (arginine, lysine, and histidine), probably due to the abilities of these amino acids to complex with heme. The results suggest an involvement in the improvement of the blood-schizonticidal activity of 8-quinolinamine when conjugated with basic amino acids. In addition, cysteine also inhibited BH formation, possibly due to its ability to reduce heme iron or decompose heme in acidic conditions. In contrast, BH formation was enhanced by amino acids with high hydrophobicity values (leucine, isoleucine, valine, methionine, and phenylalanine), with the exception of tryptophan at high temperature but was not affected in Tween-induced BH formation under normal physiological conditions. The present results can lead to further research on the development of new antimalarials by conjugating these amino acids, especially basic amino acids, with other substances, or by forming complex or small peptides that could have special effects on BH formation.

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