Applications of chromatography-ultra high-resolution MS for stable isotope-resolved metabolomics (SIRM) reconstruction of metabolic networks

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7 Scopus citations

Abstract

Metabolism is a complex network of compartmentalized and coupled chemical reactions, which often involve transfers of substructures of biomolecules, thus requiring metabolite substructures to be tracked. Stable isotope resolved metabolomics (SIRM) enables pathways reconstruction, even among chemically identical metabolites, by tracking the provenance of stable isotope-labeled substructures using NMR and ultrahigh resolution (UHR) MS. The latter can resolve and count isotopic labels in metabolites and can identify isotopic enrichment in substructures when operated in tandem MS mode. However, MS2 is difficult to implement with chromatography-based UHR-MS due to lengthy MS1 acquisition time that is required to obtain the molecular isotopologue count, which is further exacerbated by the numerous isotopologue source ions to fragment. We review here recent developments in tandem MS applications of SIRM to obtain more detailed information about isotopologue distributions in metabolites and their substructures.

Original languageEnglish
Article number115676
JournalTrAC - Trends in Analytical Chemistry
Volume123
DOIs
StatePublished - Feb 2020

Bibliographical note

Funding Information:
This work was supported by NIH grants P01CA163223-01A1 , 1U24DK097215-01A1 , 1R01CA118434-01A2 , 5R21ES025669-02 , 5R01ES22191 , 5P20GM121327 and the Metabolomics Shared Resource of the University of Kentucky Markey Cancer Center P30CA177558 .

Publisher Copyright:
© 2019 Elsevier B.V.

Keywords

  • C/N positional isotopologues
  • Data independent MS
  • Ion chromatography
  • Multiplexed stable isotope resolved metabolomics (mSIRM)
  • Nucleotides
  • Pathway reconstruction
  • Ultra high-resolution FT-MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy

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