Vitamin C biosynthesis in trypanosomes: A role for the glycosome

Abstract

The capacity to synthesize vitamin C (ascorbate) is widespread in eukaryotes but is absent from humans. The last step in the biosynthetic pathway involves the conversion of an aldonolactone substrate to ascorbate, a reaction catalyzed by members of an FAD-dependent family of oxidoreductases. Here we demonstrate that both the African trypanosome, Trypanosoma brucei, and the American trypanosome, Trypanosoma cruzi, have the capacity to synthesize vitamin C and show that this reaction occurs in a unique single-membrane organelle, the glycosome. The corresponding T. brucei flavoprotein (TbALO) obeys Michaelis-Menten kinetics and can utilize both L-galactono-␥-lactone and D-arabinono-␥-lactone as substrate, properties characteristic of plant and fungal enzymes. We could detect no activity toward the mammalian enzyme substrate L-gulono-␥-lactone. TbALO null mutants (bloodstream form) were found to display a transient growth defect, a trait that was enhanced when they were cultured in medium in which the essential serum component had been pretreated with ascorbate oxidase to deplete vitamin C. It is implicit, therefore, that bloodstream-form trypanosomes also possess a capacity for ascorbate transport.ascorbic acid ͉ FAD ͉ oxidase ͉ Trypanosoma brucei

Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2 strain

“…Jockers-Scherübl et al 25 , Wilkinsom et al 23 , Czechowicz et al 26 , and Ribeiro 6 reported the presence of one trypanothione reductase dependent on flavoenzyme nicotinamide adenine dinucleotide phosphate; this reductase catalyzes the reduction of trypanothione antioxidant, and this system is able to combat oxidative stress intracellular parasites. Studies by Krieger et al 27 showed the possibility of the parasite of this enzyme to enhance its growth and virulence.…”

“…According to Wilkinsom et al 23 parasites of the Trypanosoma genus may withdraw ascorbate from the culture medium and thus complement the deficiency of biosynthesis.…”

“…Several studies have demonstrated that T. cruzi can synthesize ascorbic acid from non-enzymatic and enzymatic systems and thereby protect themselves from ROS and RNS 10,[22][23][24] . According to Wilkinsom et al 23 parasites of the Trypanosoma genus may withdraw ascorbate from the culture medium and thus complement the deficiency of biosynthesis.…”

The Pathway via D-Galacturonate/L-Galactonate Is Significant for Ascorbate Biosynthesis in Euglena gracilis

“…Chlorella and Prototheca contained appreciable amounts of AsA, and adding Man, L-GalA and L-GalL to the Prototheca medium resulted in significantly increased levels of AsA, suggesting the presence of a Man/Gal pathway similar to that in plants (17,18). It was recently identified that a protozoan parasite, Trypanosoma brucei, possesses a functional gene encoding D-arabinono-1,4-lactone oxidase that can also oxidize L-GalL, although the exact pathway arriving at the final precursor has not been clarified yet (19). In Euglena gracilis containing high concentrations of AsA, the biosynthetic pathway was first proposed by Shigeoka et al (1).…”

Deletion of the Trypanosoma brucei Superoxide Dismutase Gene sodb1 Increases Sensitivity to Nifurtimox and Benznidazole

“…Trypanosome SODs belong to the Fe class, a group restricted to protozoans, prokaryotes, and chloroplasts. T. brucei contains four isoforms (8,11,25): TbSODA and TbSODC, which are mitochondrial, and TbSODB1 and TbSODB2, which are localized predominantly in the glycosome, a kinetoplastid-specific organelle (3,17,24). TbSODB1 and TbSODB2 also display some cytosolic localization, particularly the former (8,25).…”