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New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle.

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van Weelden, Susanne W H van Hellemond, Jaap J Opperdoes, Frederik [UCL] Tielens, Aloysius G M

We investigated whether substrate availability influences the type of energy metabolism in procyclic Trypanosoma brucei. We show that absence of glycolytic substrates (glucose and glycerol) does not induce a shift from a fermentative metabolism to complete oxidation of substrates. We also show that glucose (and even glycolysis) is not essential for normal functioning and proliferation of pleomorphic procyclic T. brucei cells. Furthermore, absence of glucose did not result in increased degradation of amino acids. Variations in availability of glucose and glycerol did result, however, in adaptations in metabolism in such a way that the glycosome was always in redox balance. We argue that it is likely that, in procyclic cells, phosphoglycerate kinase is located not only in the cytosol, but also inside glycosomes, as otherwise an ATP deficit would occur in this organelle. We demonstrate that procyclic T. brucei uses parts of the Krebs cycle for purposes other than complete degradation of mitochondrial substrates. We suggest that citrate synthase plus pyruvate dehydrogenase and malate dehydrogenase are used to transport acetyl-CoA units from the mitochondrion to the cytosol for the biosynthesis of fatty acids, a process we show to occur in proliferating procyclic cells. The part of the Krebs cycle consisting of alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase was used for the degradation of proline and glutamate to succinate. We also demonstrate that the subsequent enzymes of the Krebs cycle, succinate dehydrogenase and fumarase, are most likely used for conversion of succinate into malate, which can then be used in gluconeogenesis.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2005
Journal information "Journal of Biological Chemistry" - Vol. 280, no. 13, p. 12451-12460 (2005)
Peer reviewed yes
Publisher American Society for Biochemistry and Molecular Biology, Inc.
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Adenosine Triphosphate - chemistry - metabolism ; Animals ; Biochemistry - methods ; Cell Line ; Chromatography, High Pressure Liquid ; Citric Acid Cycle ; Cytosol - metabolism ; Energy Metabolism ; Fatty Acids - chemistry - metabolism ; Fermentation ; Glucose - chemistry - metabolism ; Glutamic Acid - chemistry ; Glycerol - chemistry - metabolism ; Glycolysis ; Models, Biological ; Models, Chemical ; Oxidation-Reduction ; Oxygen - metabolism ; Proline - chemistry ; Substrate Specificity ; Succinic Acid - chemistry ; Threonine - chemistry ; Time Factors ; Trypanosoma brucei brucei - chemistry - metabolism
Links
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Bibliographic reference van Weelden, Susanne W H ; van Hellemond, Jaap J ; Opperdoes, Frederik ; Tielens, Aloysius G M. New functions for parts of the Krebs cycle in procyclic Trypanosoma brucei, a cycle not operating as a cycle.. In: Journal of Biological Chemistry, Vol. 280, no. 13, p. 12451-12460 (2005)
Permanent URL http://hdl.handle.net/2078.1/26967