Vitamin B6 is an essential cofactor for more than 100 enzymatic reactions. Mammalian cells are unable to synthesize
vitamin B6 de novo, whereas bacteria, plants, fungi, and as shown here Plasmodium falciparum possess a functional
vitamin B6 synthesis pathway. P. falciparum expresses the
proteins Pdx1 and Pdx2, corresponding to the yeast
enzymes Snz1-p and Sno1-p, which are essential for the
vitamin B6 biosynthesis. An involvement of PfPdx1 and PfPdx2 in the de novo synthesis of
vitamin B6 was shown by complementation of
pyridoxine auxotroph yeast cells. Both plasmodial
proteins act together in the
glutaminase activity with a specific activity of 209 nmol min(-1) mg(-1) and a K(m) value for
glutamine of 1.3 mm. Incubation of the parasites with
methylene blue revealed by Northern blot analysis an elevated transcriptional level of pdx1 and pdx2, suggesting a participation of these
proteins in the defenses against
singlet oxygen. To be an active cofactor,
vitamin B6 has to be phosphorylated by the
pyridoxine kinase (PdxK). The recombinant plasmodial PdxK revealed K(m) values for the B6 vitamers
pyridoxine and
pyridoxal and for
ATP of 212, 70, and 82 microM, respectively. All three
enzymes expose a stage-specific transcription pattern within the trophozoite stage that guarantees the concurrent expression of Pdx1, Pdx2, and PdxK for the indispensable provision of
vitamin B6. The occurrence of the
vitamin B6 de novo synthesis pathway displays a potential new drug target, which can be exploited for the development of new chemotherapeutics against the human
malaria parasite P. falciparum.