Doctoral thesis
Open access

Contribution of the TCA cycle in the central carbon metabolism of apicomplexan parasites

ContributorsOppenheim, Rebecca
Defense date2015-11-19

The absence of mitochondrial pyruvate dehydrogenase complex had failed to establish a link between glycolysis and mitochondrial carboxylic acid metabolism and posed a dilemma regarding the possible alternative source(s) of mitochondrial acetyl-CoA to fuel a canonical oxidative TCA cycle in the apicomplexan parasites such as Toxoplasma gondii and Plasmodium species. Using a combination of reverse genetics and metabolic profiling by mass spectrometry, we have established that the branched chain amino acid (BCAA) degradation pathway and the 2-methylcitrate cycle which detoxifies propionyl-CoA concomitantly produced during BCAAs degradation are both dispensable and not the source of mitochondrial acetyl-CoA for these parasites. Rather we provide evidence that the BCKDH complex has evolved towards the use of glycolytic pyruvate and act as a substitute for the PDH complex to generate mitochondrial acetyl-CoA and sustain a complete TCA cycle. Furthermore, we investigated the routes to generate cytoplasmic acetyl-CoA and their importance in T. gondii.

  • Toxoplasma gondii
  • Plasmodium species
  • Mitochondrion
  • Apicoplast
  • Central carbon metabolism
  • Acetyl-CoA
  • TCA cycle
  • 2-methycitrate cycle
  • Branched chain ketoacid dehydrogenase complex
Citation (ISO format)
OPPENHEIM, Rebecca. Contribution of the TCA cycle in the central carbon metabolism of apicomplexan parasites. 2015. doi: 10.13097/archive-ouverte/unige:80156
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