ArticleMolecular microbiology2013
The threonine degradation pathway of the Trypanosoma brucei procyclic form: the main carbon source for lipid biosynthesis is under metabolic control.
Article in Molecular microbiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 76 citations in OpenAlex.
- Glycerol metabolism triggers trypanosome differentiation into transmissible forms in mammalian tissue-like conditions.Nature communications · 2026Article
- Modulation of succinyl-CoA:3-ketoacid CoA transferase activity by a single amino acid residue in acetate:succinate CoA transferase from Trypanosoma brucei, the causative agent of African sleeping sickness.Protein science : a publication of the Protein Society · 2026Article
- Endosymbiosis in trypanosomatids: the bacterium regulates the intermediate and oxidative metabolism of the host cell.mSphere · 2025Article
- GArNet: A Genetic Algorithm-Based Protein Redesign Approach to Optimize Mutation Combinations Informed by Network Theory.Journal of chemical information and modeling · 2025Article
- Energy metabolism inmBio · 2025Review
- The glycosomal ATP-dependent phosphofructokinase of Trypanosoma brucei operates also in the gluconeogenic direction.PLoS biology · 2025Article
- The role of l-serine and l-threonine in the energy metabolism and nutritional stress response ofmSphere · 2025Article
- Inhibition of L-threonine dehydrogenase from Trypanosoma cruzi reduces glycine and acetate production and interferes with parasite growth and viability.The Journal of biological chemistry · 2025Article
- Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant.Scientific reports · 2024Article
- Effect of sunitinib against Echinococcus multilocularis through inhibition of VEGFA-induced angiogenesis.Parasites & vectors · 2023Article
- Glucose metabolism sustains heme-induced Trypanosoma cruzi epimastigote growth in vitro.PLoS neglected tropical diseases · 2023Article
- Mitochondrion of the Trypanosoma brucei long slender bloodstream form is capable of ATP production by substrate-level phosphorylation.PLoS pathogens · 2023Article
- A novel lipase with dual localisation in Trypanosoma brucei.Scientific reports · 2022Article
- Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery.Metabolomics : Official journal of the Metabolomic Society · 2022Review
- Fatty acid uptake inFrontiers in cellular and infection microbiology · 2022Review
- Developmental changes and metabolic reprogramming during establishment of infection and progression of Trypanosoma brucei brucei through its insect host.PLoS neglected tropical diseases · 2021Article
- The X-ray structure of L-threonine dehydrogenase from the common hospital pathogen Clostridium difficile.Acta crystallographica. Section F, Structural biology communications · 2021Article
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
- Procyclic trypanosomes recycle glucose catabolites and TCA cycle intermediates to stimulate growth in the presence of physiological amounts of proline.PLoS pathogens · 2021Article
- The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei.Biochimica et biophysica acta. Bioenergetics · 2020Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The Trypanosoma brucei procyclic form resides within the digestive tract of its insect vector, where it exploits amino acids as carbon sources. Threonine is the amino acid most rapidly consumed by this parasite, however its role is poorly understood. Here, we show that the procyclic trypanosomes grown in rich medium only use glucose and threonine for lipid biosynthesis, with threonine's contribution being ∼ 2.5 times higher than that of glucose. A combination of reverse genetics and NMR analysis of excreted end-products from threonine and glucose metabolism, shows that acetate, which feeds lipid biosynthesis, is also produced primarily from threonine. Interestingly, the first enzymatic step of the threonine degradation pathway, threonine dehydrogenase (TDH, EC 1.1.1.103), is under metabolic control and plays a key role in the rate of catabolism. Indeed, a trypanosome mutant deleted for the phosphoenolpyruvate decarboxylase gene (PEPCK, EC 4.1.1.49) shows a 1.7-fold and twofold decrease of TDH protein level and activity, respectively, associated with a 1.8-fold reduction in threonine-derived acetate production. We conclude that TDH expression is under control and can be downregulated in response to metabolic perturbations, such as in the PEPCK mutant in which the glycolytic metabolic flux was redirected towards acetate production.
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