Evidence map›Paper›PMID 25775470›Full record

ArticlePLoS pathogens2015

Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

Darren J Creek, Muriel Mazet, Fiona Achcar, Jana Anderson, Dong-Hyun Kim, Ruwida Kamour, Pauline Morand, Yoann Millerioux, Marc Biran, Eduard J Kerkhoven and 7 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
12.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 123 citations in OpenAlex.

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  8. Frontiers in microbiology · 2024
    Article
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  19. Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery.Metabolomics : Official journal of the Metabolomic Society · 2022
    Review
  20. Article

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 12 institutions in 5 countries.

Darren J CreekDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Parkville, Victoria, Australia.
Muriel MazetCentre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, CNRS UMR-5536, Bordeaux, France.
Fiona AchcarWellcome Trust Centre of Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Jana AndersonDepartment of Public Health, Institute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Dong-Hyun KimCentre for Analytical Bioscience, School of Pharmacy, University of Nottingham, University Park, Nottingham, United Kingdom.
Ruwida KamourDepartment of Medicinal and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tripoli, Tripoli, Libya.
Pauline MorandCentre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, CNRS UMR-5536, Bordeaux, France.
Yoann MilleriouxCentre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, CNRS UMR-5536, Bordeaux, France.
Marc BiranCentre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, CNRS UMR-5536, Bordeaux, France.
Eduard J KerkhovenSystems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
Achuthanunni ChokkathukalamGlasgow Polyomics, Wolfson Wohl Cancer Research Centre, Garscube Campus, College of Medical Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Stefan K WeidtGlasgow Polyomics, Wolfson Wohl Cancer Research Centre, Garscube Campus, College of Medical Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Karl E V BurgessGlasgow Polyomics, Wolfson Wohl Cancer Research Centre, Garscube Campus, College of Medical Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Rainer BreitlingManchester Institute of Biotechnology, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
David G WatsonStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
Frédéric BringaudCentre de Résonance Magnétique des Systèmes Biologiques, Université de Bordeaux, CNRS UMR-5536, Bordeaux, France.
Michael P BarrettWellcome Trust Centre of Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Glasgow Polyomics, Wolfson Wohl Cancer Research Centre, Garscube Campus, College of Medical Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
University of Glasgow · GBCentre National de la Recherche Scientifique · FRCentre de Résonance Magnétique des Systèmes Biologiques · FRChalmers University of Technology · SEMonash University · AUUniversité de Bordeaux · FRUniversity of Manchester · GBUniversity of Nottingham · GBUniversity of Strathclyde · GBUniversity of Tripoli · LYWellcome Centre for Molecular Parasitology · GBWellcome Trust · GB

Funding

Biotechnology and Biological Sciences Research Council BB/I004599/1Wellcome Trust 085349Wellcome Trust 104111
6 · The paper itself

Abstract

Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

Indexed as

AnimalsCells, CulturedGlucoseGlycerolMetabolic Networks and PathwaysMetabolomicsOxidation-ReductionPentose Phosphate PathwaySuccinic AcidTrypanosoma brucei bruceiGlucoseGlycerolSuccinic Acid

Identifiers

PMID25775470
PMCPMC4361558
OpenAlexW2170954647

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.