en
Doctoral thesis
Open access
English

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

ContributorsOppenheim, Rebecca
Defense date2015-11-19
Abstract

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.

eng
Keywords
  • 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
Main files (1)
Thesis
accessLevelPublic
Identifiers
728views
984downloads

Technical informations

Creation01/27/2016 5:24:00 PM
First validation01/27/2016 5:24:00 PM
Update time03/15/2023 12:06:54 AM
Status update03/15/2023 12:06:53 AM
Last indexation05/02/2024 5:16:10 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack