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Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine

INTRODUCTION: Despite the use of buffering agents the (1)H NMR spectra of biofluid samples in metabolic profiling investigations typically suffer from extensive peak frequency shifting between spectra. These chemical shift changes are mainly due to differences in pH and divalent metal ion concentrat...

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Autores principales: Tredwell, Gregory D., Bundy, Jacob G., De Iorio, Maria, Ebbels, Timothy M. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025509/
https://www.ncbi.nlm.nih.gov/pubmed/27729829
http://dx.doi.org/10.1007/s11306-016-1101-y
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author Tredwell, Gregory D.
Bundy, Jacob G.
De Iorio, Maria
Ebbels, Timothy M. D.
author_facet Tredwell, Gregory D.
Bundy, Jacob G.
De Iorio, Maria
Ebbels, Timothy M. D.
author_sort Tredwell, Gregory D.
collection PubMed
description INTRODUCTION: Despite the use of buffering agents the (1)H NMR spectra of biofluid samples in metabolic profiling investigations typically suffer from extensive peak frequency shifting between spectra. These chemical shift changes are mainly due to differences in pH and divalent metal ion concentrations between the samples. This frequency shifting results in a correspondence problem: it can be hard to register the same peak as belonging to the same molecule across multiple samples. The problem is especially acute for urine, which can have a wide range of ionic concentrations between different samples. OBJECTIVES: To investigate the acid, base and metal ion dependent (1)H NMR chemical shift variations and limits of the main metabolites in a complex biological mixture. METHODS: Urine samples from five different individuals were collected and pooled, and pre-treated with Chelex-100 ion exchange resin. Urine samples were either treated with either HCl or NaOH, or were supplemented with various concentrations of CaCl(2), MgCl(2), NaCl or KCl, and their (1)H NMR spectra were acquired. RESULTS: Nonlinear fitting was used to derive acid dissociation constants and acid and base chemical shift limits for peaks from 33 identified metabolites. Peak pH titration curves for a further 65 unidentified peaks were also obtained for future reference. Furthermore, the peak variations induced by the main metal ions present in urine, Na(+), K(+), Ca(2+) and Mg(2+), were also measured. CONCLUSION: These data will be a valuable resource for (1)H NMR metabolite profiling experiments and for the development of automated metabolite alignment and identification algorithms for (1)H NMR spectra. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-016-1101-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-50255092016-10-09 Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine Tredwell, Gregory D. Bundy, Jacob G. De Iorio, Maria Ebbels, Timothy M. D. Metabolomics Original Article INTRODUCTION: Despite the use of buffering agents the (1)H NMR spectra of biofluid samples in metabolic profiling investigations typically suffer from extensive peak frequency shifting between spectra. These chemical shift changes are mainly due to differences in pH and divalent metal ion concentrations between the samples. This frequency shifting results in a correspondence problem: it can be hard to register the same peak as belonging to the same molecule across multiple samples. The problem is especially acute for urine, which can have a wide range of ionic concentrations between different samples. OBJECTIVES: To investigate the acid, base and metal ion dependent (1)H NMR chemical shift variations and limits of the main metabolites in a complex biological mixture. METHODS: Urine samples from five different individuals were collected and pooled, and pre-treated with Chelex-100 ion exchange resin. Urine samples were either treated with either HCl or NaOH, or were supplemented with various concentrations of CaCl(2), MgCl(2), NaCl or KCl, and their (1)H NMR spectra were acquired. RESULTS: Nonlinear fitting was used to derive acid dissociation constants and acid and base chemical shift limits for peaks from 33 identified metabolites. Peak pH titration curves for a further 65 unidentified peaks were also obtained for future reference. Furthermore, the peak variations induced by the main metal ions present in urine, Na(+), K(+), Ca(2+) and Mg(2+), were also measured. CONCLUSION: These data will be a valuable resource for (1)H NMR metabolite profiling experiments and for the development of automated metabolite alignment and identification algorithms for (1)H NMR spectra. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-016-1101-y) contains supplementary material, which is available to authorized users. Springer US 2016-09-15 2016 /pmc/articles/PMC5025509/ /pubmed/27729829 http://dx.doi.org/10.1007/s11306-016-1101-y Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Tredwell, Gregory D.
Bundy, Jacob G.
De Iorio, Maria
Ebbels, Timothy M. D.
Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine
title Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine
title_full Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine
title_fullStr Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine
title_full_unstemmed Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine
title_short Modelling the acid/base (1)H NMR chemical shift limits of metabolites in human urine
title_sort modelling the acid/base (1)h nmr chemical shift limits of metabolites in human urine
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025509/
https://www.ncbi.nlm.nih.gov/pubmed/27729829
http://dx.doi.org/10.1007/s11306-016-1101-y
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