Darren J. Creek
Probing the Metabolic Network in Bloodstream-Form Trypanosoma brucei Using Untargeted Metabolomics with Stable Isotope Labelled Glucose
Creek, Darren J.; KIM, DONG-HYUN; Mazet, Muriel; Achcar, Fiona; Anderson, Jana; Kamour, Ruwida; Morand, Pauline; Millerioux, Yoann; Biran, Marc; Kerkhoven, Eduard J.; Chokkathukalam, Achuthanunni; Weidt, Stefan K.; Burgess, Karl E. V.; Breitling, Rainer; Watson, David G.; Bringaud, Fr�d�ric; Barrett, Michael P.
Authors
DONG-HYUN KIM Dong-hyun.Kim@nottingham.ac.uk
Associate Professor
Muriel Mazet
Fiona Achcar
Jana Anderson
Ruwida Kamour
Pauline Morand
Yoann Millerioux
Marc Biran
Eduard J. Kerkhoven
Achuthanunni Chokkathukalam
Stefan K. Weidt
Karl E. V. Burgess
Rainer Breitling
David G. Watson
Fr�d�ric Bringaud
Michael P. Barrett
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.
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 19, 2015 |
Publication Date | Mar 1, 2015 |
Deposit Date | May 23, 2018 |
Print ISSN | 1553-7366 |
Electronic ISSN | 1553-7374 |
Publisher | Public Library of Science |
Peer Reviewed | Peer Reviewed |
Volume | 11 |
Issue | 3 |
DOI | https://doi.org/10.1371/journal.ppat.1004689 |
Public URL | https://nottingham-repository.worktribe.com/output/1102934 |
Publisher URL | https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004689 |
PMID | 25775470 |
You might also like
Evidence for large-scale gene-by-smoking interaction effects on pulmonary function
(2017)
Journal Article
Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana
(2017)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search