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

Qiushi Sun; Teresa W.M. Fan; Andrew N. Lane; Richard M. Higashi

doi:10.1016/j.trac.2019.115676

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

Qiushi Sun, Teresa W.M. Fan, Andrew N. Lane, Richard M. Higashi

Research output: Contribution to journal › Review article › peer-review

11 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 language	English
Article number	115676
Journal	TrAC - Trends in Analytical Chemistry
Volume	123
DOIs	https://doi.org/10.1016/j.trac.2019.115676
State	Published - Feb 2020

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.

Funding

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 .

Funders	Funder number
National Institutes of Health (NIH)	5P20GM121327, 5R01ES22191, P01CA163223-01A1, 1U24DK097215-01A1, 5R21ES025669-02, 1R01CA118434-01A2
University of Kentucky Markey Cancer Center	P30CA177558

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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10.1016/j.trac.2019.115676

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

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.",

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

author = "Qiushi Sun and Fan, {Teresa W.M.} and Lane, {Andrew N.} and Higashi, {Richard M.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2020",

month = feb,

doi = "10.1016/j.trac.2019.115676",

language = "English",

volume = "123",

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AU - Sun, Qiushi

AU - Fan, Teresa W.M.

AU - Lane, Andrew N.

AU - Higashi, Richard M.

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - C/N positional isotopologues

KW - Data independent MS

KW - Ion chromatography

KW - Multiplexed stable isotope resolved metabolomics (mSIRM)

KW - Nucleotides

KW - Pathway reconstruction

KW - Ultra high-resolution FT-MS

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DO - 10.1016/j.trac.2019.115676

M3 - Review article

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VL - 123

JO - TrAC - Trends in Analytical Chemistry

JF - TrAC - Trends in Analytical Chemistry

M1 - 115676

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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