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

被引:12
作者
Sun, Qiushi [1 ,4 ]
Fan, Teresa W-M [1 ,2 ,3 ]
Lane, Andrew N. [1 ,2 ,3 ]
Higashi, Richard M. [1 ,2 ,3 ]
机构
[1] Univ Kentucky, Ctr Environm & Syst Biochem, Lexington, KY 40539 USA
[2] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY 40539 USA
[3] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40539 USA
[4] Yale Sch Med, Dept Internal Med Endocrinol, New Haven, CT 06519 USA
关键词
Ion chromatography; Ultra high-resolution FT-MS; Data independent MS2; C-13/N-15 positional isotopologues; Multiplexed stable isotope resolved metabolomics (mSIRM); Pathway reconstruction; Nucleotides; DATA-INDEPENDENT-ACQUISITION; ELECTROPHORESIS-MASS SPECTROMETRY; NECK-CANCER CELLS; ION CHROMATOGRAPHY; LUNG-CANCER; CAPILLARY-ELECTROPHORESIS; FLUX ANALYSIS; LC-MS; GLUTAMINE-METABOLISM; ANIONIC METABOLITES;
D O I
10.1016/j.trac.2019.115676
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
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. (C) 2019 Elsevier B.V. All rights reserved.
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页数:9
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