The apicomplexan parasite Toxoplasma gondii generates pyridoxal phosphate de novo

Knöckel, Julia; Müller, Ingrid; Bergmann, Bärbel; Walter, Rolf D.; Wrenger, Carsten

doi:10.1016/j.molbiopara.2006.12.005

Cited by 18 publications

(15 citation statements)

References 25 publications

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“…Moreover, we demonstrated a homologous pathway in the other apicomplexan parasite Toxoplasma gondii, where PLP synthesis also is a product of the single copy genes Pdx1 and Pdx2 (17). The two proteins need to act together for enzyme activity, similar to the homologous yeast proteins SNZ1 and SNO1 (6).…”

Section: Alternative Pathways Of Vitamin B6 Biosynthesismentioning

confidence: 86%

“…The functionality of the two proteins of the apicomplexan parasites was verified by complementation of vitamin B6-deficient yeast strains (16). As is the case for yeast, in apicomplexa vitamin B6 is directly synthesized in its active form PLP (7,8,17,18). The Pdx1 protein is responsible for the creation of PLP by utilizing pentose, triose as well as ammonia.…”

Section: Alternative Pathways Of Vitamin B6 Biosynthesismentioning

confidence: 98%

“…The ammonia is provided by the Pdx2 protein, which possesses glutaminase activity. Interestingly, the activity of Pdx1 is not dependent on the presence of Pdx2 if glutamine is replaced by ammonia, whereas the activity of Pdx2 relies on its interaction with Pdx1 (16,17).…”

Section: Alternative Pathways Of Vitamin B6 Biosynthesismentioning

confidence: 99%

“…Enzymes involved in vitamin B1 synthesis as shown for P. falciparum are apparently absent in the genome of the apicomplexan relatives E. tenella (http://www.sanger.ac.uk/ Projects/E_tenella/), and T. gondii (http://www.toxodb.org/ toxo/home.jsp) (17). This major difference poses questions about evolutionary adaptation of these parasites to their hosts.…”

Section: Does Vitamin B1 Biosynthesis Occur In Other Apicomplexan Parmentioning

confidence: 99%

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Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Wrenger

Knöckel

Walter

et al. 2008

Braz J Med Biol Res

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Vitamins are essential compounds mainly involved in acting as enzyme co-factors or in response to oxidative stress. In the last two years it became apparent that apicomplexan parasites are able to generate B vitamers such as vitamin B1 and B6 de novo. The biosynthesis pathways responsible for vitamin generation are considered as drug targets, since both provide a high degree of selectivity due to their absence in the human host. This report updates the current knowledge about vitamin B1 and B6 biosynthesis in malaria and other apicomplexan parasites. Owing to the urgent need for novel antimalarials, the significance of the biosynthesis and salvage of these vitamins is critically discussed in terms of parasite survival and their exploitation for drug development.

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Section: Alternative Pathways Of Vitamin B6 Biosynthesismentioning

confidence: 86%

Section: Alternative Pathways Of Vitamin B6 Biosynthesismentioning

confidence: 98%

Section: Alternative Pathways Of Vitamin B6 Biosynthesismentioning

confidence: 99%

Section: Does Vitamin B1 Biosynthesis Occur In Other Apicomplexan Parmentioning

confidence: 99%

See 2 more Smart Citations

Vitamin B1 and B6 in the malaria parasite: requisite or dispensable?

Wrenger

Knöckel

Walter

et al. 2008

Braz J Med Biol Res

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“…Many of the PLP-dependent enzymes are essential and therein offer the possibility to target diseases [2]. Whereas humans are entirely dependent on the uptake of vitamin B 6 from their diet, bacteria, fungi and plants as well as the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii possess a de novo vitamin B 6 -synthesis pathway [3][4][5][6]. Vitamin B 6 can be synthesized in two ways.…”

Section: Introductionmentioning

confidence: 99%

The antioxidative effect of de novo generated vitamin B6 in Plasmodium falciparum validated by protein interference

Knöckel

Müller

Butzloff

et al. 2012

Biochemical Journal

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The malaria parasite Plasmodium falciparum is able to synthesize de novo PLP (pyridoxal 5'-phosphate), the active form of vitamin B6. In the present study, we have shown that the de novo synthesized PLP is used by the parasite to detoxify 1O2 (singlet molecular oxygen), a highly destructive reactive oxygen species arising from haemoglobin digestion. The formation of 1O2 and the response of the parasite were monitored by live-cell fluorescence microscopy, by transcription analysis and by determination of PLP levels in the parasite. Pull-down experiments of transgenic parasites overexpressing the vitamin B6-biosynthetic enzymes PfPdx1 and PfPdx2 clearly demonstrated an interaction of the two proteins in vivo which results in an elevated PLP level from 12.5 μM in wild-type parasites to 36.6 μM in the PfPdx1/PfPdx2-overexpressing cells and thus to a higher tolerance towards 1O2. In contrast, by applying the dominant-negative effect on the cellular level using inactive mutants of PfPdx1 and PfPdx2, P. falciparum becomes susceptible to 1O2. Our results demonstrate clearly the crucial role of vitamin B6 biosynthesis in the detoxification of 1O2 in P. falciparum. Besides the known role of PLP as a cofactor of many essential enzymes, this second important task of the vitamin B6 de novo synthesis as antioxidant emphasizes the high potential of this pathway as a target of new anti-malarial drugs.

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