A carbonyl capture approach for profiling oxidized metabolites in cell extracts

Stephanie J. Mattingly, Tao Xu, Michael H. Nantz, Richard M. Higashi, Teresa W M Fan

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Fourier-transform ion-cyclotron resonance mass spectrometry (FT-ICR-MS) detection of oxidized cellular metabolites is described using isotopologic, carbonyl-selective derivatizing agents that integrate aminooxy functionality for carbonyl capture, quaternary nitrogen for electrospray enhancement, and a hydrophobic domain for sample cleanup. These modular structural features enable rapid, sensitive analysis of complex mixtures of metabolite-derivatives by FT-ICR-MS via continuous nanoelectrospray infusion. Specifically, this approach can be used to globally assess levels of low abundance and labile aldehyde and ketone metabolites quantitatively and in high throughput manner. These metabolites are often key and unique indicators of various biochemical pathways and their perturbations. Analysis of lung adenocarcinoma A549 cells established a profile of carbonyl metabolites spanning multiple structural classes. We also demonstrate a procedure for metabolite quantification using pyruvate as a model analyte.

Original languageEnglish (US)
Pages (from-to)989-996
Number of pages8
JournalMetabolomics
Volume8
Issue number6
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Cyclotrons
Fourier Analysis
Metabolites
Cell Extracts
Mass Spectrometry
Ions
Ketones
Complex Mixtures
Pyruvic Acid
Aldehydes
Cyclotron resonance
Nitrogen
Mass spectrometry
Fourier transforms
Throughput
Derivatives
A549 Cells
Adenocarcinoma of lung

Keywords

  • α-ketoglutarate
  • Aldehyde
  • Cellular oxidation state
  • Ketone
  • Mass spectrometry
  • Metabolite profiling
  • Oxaloacetate
  • Pyruvate

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Mattingly, S. J., Xu, T., Nantz, M. H., Higashi, R. M., & Fan, T. W. M. (2012). A carbonyl capture approach for profiling oxidized metabolites in cell extracts. Metabolomics, 8(6), 989-996. https://doi.org/10.1007/s11306-011-0395-z

A carbonyl capture approach for profiling oxidized metabolites in cell extracts. / Mattingly, Stephanie J.; Xu, Tao; Nantz, Michael H.; Higashi, Richard M.; Fan, Teresa W M.

In: Metabolomics, Vol. 8, No. 6, 12.2012, p. 989-996.

Research output: Contribution to journalArticle

Mattingly, SJ, Xu, T, Nantz, MH, Higashi, RM & Fan, TWM 2012, 'A carbonyl capture approach for profiling oxidized metabolites in cell extracts', Metabolomics, vol. 8, no. 6, pp. 989-996. https://doi.org/10.1007/s11306-011-0395-z
Mattingly, Stephanie J. ; Xu, Tao ; Nantz, Michael H. ; Higashi, Richard M. ; Fan, Teresa W M. / A carbonyl capture approach for profiling oxidized metabolites in cell extracts. In: Metabolomics. 2012 ; Vol. 8, No. 6. pp. 989-996.
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