ArticleThe Biochemical journal2012
Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases.Tropical medicine and infectious disease · 2025Review
- Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads.Biomolecules · 2024Review
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Elucidation of sterol biosynthesis pathway and its co-regulation with fatty acid biosynthesis in the oleaginous marine protistFrontiers in bioengineering and biotechnology · 2023Article
- Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense.Nature communications · 2022Article
- Steroidal Antimetabolites Protect Mice againstMolecules (Basel, Switzerland) · 2022Article
- Using microbial metalo-aminopeptidases as targets in human infectious diseases.Microbial cell (Graz, Austria) · 2021Review
- Phytosterol Profiles, Genomes and Enzymes - An Overview.Frontiers in plant science · 2021Review
- Identification of Four Amoebicidal Nontoxic Compounds by a Molecular Docking Screen ofACS infectious diseases · 2019Article
- Prenylquinones in Human Parasitic Protozoa: Biosynthesis, Physiological Functions, and Potential as Chemotherapeutic Targets.Molecules (Basel, Switzerland) · 2019Review
- Microbial Sterolomics as a Chemical Biology Tool.Molecules (Basel, Switzerland) · 2018Review
- Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri.PLoS pathogens · 2018Article
- De novo biosynthesis of sterols and fatty acids in the Trypanosoma brucei procyclic form: Carbon source preferences and metabolic flux redistributions.PLoS pathogens · 2018Article
- The Uptake and Metabolism of Amino Acids, and Their Unique Role in the Biology of Pathogenic Trypanosomatids.Pathogens (Basel, Switzerland) · 2018Review
- CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM).PLoS neglected tropical diseases · 2017Article
- Sterol methyltransferase a target for anti-amoeba therapy: towards transition state analog and suicide substrate drug design.Journal of lipid research · 2017Article
- Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts.Scientific reports · 2017Article
- Metabolic reprogramming during theF1000Research · 2017Review
- Trypanosoma brucei CYP51: Essentiality and Targeting Therapy in an Experimental Model.PLoS neglected tropical diseases · 2016Article
- Sterol metabolism in the filasterean Capsaspora owczarzaki has features that resemble both fungi and animals.Open biology · 2016Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Trypanosoma brucei is the protozoan parasite that causes African trypanosomiasis, a neglected disease of people and animals. Co-metabolite analysis, labelling studies using [methyl-2H3]-methionine and substrate/product specificities of the cloned 24-SMT (sterol C24-methyltransferase) and 14-SDM (sterol C14demethylase) from T. brucei afforded an uncommon sterol metabolic network that proceeds from lanosterol and 31-norlanosterol to ETO [ergosta-5,7,25(27)-trien-3β-ol], 24-DTO [dimethyl ergosta-5,7,25(27)-trienol] and ergosterol [ergosta-5,7,22(23)-trienol]. To assess the possible carbon sources of ergosterol biosynthesis, specifically 13C-labelled specimens of lanosterol, acetate, leucine and glucose were administered to T. brucei and the 13C distributions found were in accord with the operation of the acetate-mevalonate pathway, with leucine as an alternative precursor, to ergostenols in either the insect or bloodstream form. In searching for metabolic signatures of procyclic cells, we observed that the 13C-labelling treatments induce fluctuations between the acetyl-CoA (mitochondrial) and sterol (cytosolic) synthetic pathways detected by the progressive increase in 13C-ergosterol production (control<[2-(13)C]leucine<[2-(13)C]acetate<[1-(13)C]glucose) and corresponding depletion of cholesta-5,7,24-trienol. We conclude that anabolic fluxes originating in mitochondrial metabolism constitute a flexible part of sterol synthesis that is further fluctuated in the cytosol, yielding distinct sterol profiles in relation to cell demands on growth.
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