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

doi:10.1007/s11306-011-0395-z

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 journal › Article › peer-review

29 Scopus citations

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 language	English
Pages (from-to)	989-996
Number of pages	8
Journal	Metabolomics
Volume	8
Issue number	6
DOIs	https://doi.org/10.1007/s11306-011-0395-z
State	Published - Dec 2012

Bibliographical note

Funding Information:
Acknowledgments We acknowledge financial support from NIH 1RO1CA118434-01A2 (TWMF), 3RO1CA118434-02S1 (TWMF), Kentucky Lung Cancer Research Program OGMB101380 (TWMF), and the University of Louisville Clinical & Translational Science Pilot Grant 20003. The FT-ICR-MS instrumentation at the Center for Regulatory and Environmental Analytical Metabolomics Mass Spectrometry Facility was funded by NSF/EPSCoR grant # EPS-0447479 (TWMF).

Funding

Acknowledgments We acknowledge financial support from NIH 1RO1CA118434-01A2 (TWMF), 3RO1CA118434-02S1 (TWMF), Kentucky Lung Cancer Research Program OGMB101380 (TWMF), and the University of Louisville Clinical & Translational Science Pilot Grant 20003. The FT-ICR-MS instrumentation at the Center for Regulatory and Environmental Analytical Metabolomics Mass Spectrometry Facility was funded by NSF/EPSCoR grant # EPS-0447479 (TWMF).

Funders	Funder number
Kentucky Lung Cancer Research Program	OGMB101380
NSF-Kentucky EPSCoR	EPS-0447479
TWMF	3RO1CA118434-02S1
National Institutes of Health (NIH)	1RO1CA118434-01A2
University of Louisville	20003

Keywords

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

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Clinical Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s11306-011-0395-z

Cite this

@article{0a910ed6293b4947bea985b4eae6e123,

title = "A carbonyl capture approach for profiling oxidized metabolites in cell extracts",

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.",

keywords = "Aldehyde, Cellular oxidation state, Ketone, Mass spectrometry, Metabolite profiling, Oxaloacetate, Pyruvate, α-ketoglutarate",

author = "Mattingly, {Stephanie J.} and Tao Xu and Nantz, {Michael H.} and Higashi, {Richard M.} and Fan, {Teresa W.M.}",

note = "Funding Information: Acknowledgments We acknowledge financial support from NIH 1RO1CA118434-01A2 (TWMF), 3RO1CA118434-02S1 (TWMF), Kentucky Lung Cancer Research Program OGMB101380 (TWMF), and the University of Louisville Clinical & Translational Science Pilot Grant 20003. The FT-ICR-MS instrumentation at the Center for Regulatory and Environmental Analytical Metabolomics Mass Spectrometry Facility was funded by NSF/EPSCoR grant # EPS-0447479 (TWMF).",

year = "2012",

month = dec,

doi = "10.1007/s11306-011-0395-z",

language = "English",

volume = "8",

pages = "989--996",

number = "6",

}

TY - JOUR

T1 - A carbonyl capture approach for profiling oxidized metabolites in cell extracts

AU - Mattingly, Stephanie J.

AU - Xu, Tao

AU - Nantz, Michael H.

AU - Higashi, Richard M.

AU - Fan, Teresa W.M.

N1 - Funding Information: Acknowledgments We acknowledge financial support from NIH 1RO1CA118434-01A2 (TWMF), 3RO1CA118434-02S1 (TWMF), Kentucky Lung Cancer Research Program OGMB101380 (TWMF), and the University of Louisville Clinical & Translational Science Pilot Grant 20003. The FT-ICR-MS instrumentation at the Center for Regulatory and Environmental Analytical Metabolomics Mass Spectrometry Facility was funded by NSF/EPSCoR grant # EPS-0447479 (TWMF).

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

KW - Aldehyde

KW - Cellular oxidation state

KW - Ketone

KW - Mass spectrometry

KW - Metabolite profiling

KW - Oxaloacetate

KW - Pyruvate

KW - α-ketoglutarate

UR - http://www.scopus.com/inward/record.url?scp=84868347609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868347609&partnerID=8YFLogxK

U2 - 10.1007/s11306-011-0395-z

DO - 10.1007/s11306-011-0395-z

M3 - Article

AN - SCOPUS:84868347609

SN - 1573-3882

VL - 8

SP - 989

EP - 996

JO - Metabolomics

JF - Metabolomics

IS - 6

ER -

A carbonyl capture approach for profiling oxidized metabolites in cell extracts

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this