Probing the Metabolic Network in Bloodstream-Form Trypanosoma brucei Using Untargeted Metabolomics with Stable Isotope Labelled Glucose
Artikel i vetenskaplig tidskrift, 2015

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.


D. J. Creek

Monash University

M. Mazet

Centre de Resonance Magnetique des Systemes Biologiques

F. Achcar

Wellcome Trust Centre for Molecular Parasitology

J. Anderson

University of Glasgow

D. H. Kim

University of Nottingham

R. Kamour

University of Tripoli

P. Morand

Centre de Resonance Magnetique des Systemes Biologiques

University of California

Y. Millerioux

Centre de Resonance Magnetique des Systemes Biologiques

M. Biran

Centre de Resonance Magnetique des Systemes Biologiques

Eduard Kerkhoven

Chalmers, Biologi och bioteknik, Systembiologi

A. Chokkathukalam

University of Glasgow

S. K. Weidt

University of Glasgow

K. E. V. Burgess

University of Glasgow

R. Breitling

University of Manchester

D. G. Watson

University of Strathclyde

F. Bringaud

Centre de Resonance Magnetique des Systemes Biologiques

M. P. Barrett

University of Glasgow

Wellcome Trust Centre for Molecular Parasitology

PLoS Pathogens

1553-7366 (ISSN) 1553-7374 (eISSN)

Vol. 11 1-25 e1004689


Biologisk systematik