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Role of branched-chain amino acid degradation and methylcitrate cycle pathways in carbon acquisition by Toxoplasma gondii

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Defense Thèse de doctorat : Univ. Genève, 2011 - Sc. 4363 - 2011/05/31
Abstract Toxoplasma gondii parasites replicate rapidly within a parasitophorous vacuole (PV) in the cytosol of host cells. The PV protects the parasite but restricts access to host cell nutrients. The aim of this project was to identify, the source of acetyl-CoA fuelling the TCA cycle. We identified the branched-chain amino acid (BCAA) degradation pathway as a potential source of acetyl-CoA and propionyl-CoA in T. gondii. Concomitantly, we identified the presence of the 2-methylcitrate cycle in coccidians as a potential pathway for detoxifying propionyl-CoA. We hypothesized that the Apicomplexan BCKDH complex may have evolved towards the use of pyruvate as a substrate, acting as a substitute for the PDH complex. Preliminary results using LC-MS suggest that the BCKDH complex in T. gondii has evolved towards using glucose as a substrate for acetyl-CoA production. T. gondii lipidome preliminary study also revealed a remodelling of host lipids upon infection with T. gondii.
Keywords Toxoplasma gondiiCarbon metabolismMitochondrionMethylcitrate cycleIntracelullar parasite
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URN: urn:nbn:ch:unige-178515
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LIMENITAKIS, Julien. Role of branched-chain amino acid degradation and methylcitrate cycle pathways in carbon acquisition by Toxoplasma gondii. Université de Genève. Thèse, 2011. https://archive-ouverte.unige.ch/unige:17851

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Deposited on : 2011-12-20

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