Haem biosynthesis appeared to be a target of malaria therapy because 5-aminolevulinic acid (ALA), a haem biosynthesis starting material, with light exposure or a high amount of ALA alone reduced Plasmodium falciparum growth to undetectable level. However, the administration of a high dose of ALA is unrealistic for clinical therapy. We found that Fe(2+) enhanced P. falciparum-killing potency of ALA and significantly inhibited the parasite growth. The intermediates of haem biosynthesis localized to the parasite organelles, and coproporphyrin III was the most accumulated intermediate. These novel findings may lead to development of a new anti-malarial drug using ALA and Fe(2+).
Keywords: 5-aminolevulinic acid (ALA); Haem synthesis; Plasmodium falciparum; malaria.