Class selection of amino acid metabolites in body fluids using chemical derivatization and their enhanced 13C NMR

Narasimhamurthy Shanaiah, M. Aruni Desilva, G. A.Nagana Gowda, Michael A. Raftery, Bryan E. Hainline, Daniel Raftery

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

We report a chemical derivatization method that selects a class of metabolites from a complex mixture and enhances their detection by 13C NMR. Acetylation of amines directly in aqueous medium with 1,1′-13C2 acetic anhydride is a simple method that creates a high sensitivity and quantitative label in complex biofluids with minimal sample pretreatment. Detection using either 1D or 2D 13C NMR experiments produces highly resolved spectra with improved sensitivity. Experiments to identify and compare amino acids and related metabolites in normal human urine and serum samples as well as in urine from patients with the inborn errors of metabolism tyrosinemia type II, argininosuccinic aciduria, homocystinuria, and phenylketonuria demonstrate the method. The use of metabolite derivatization and 13C NMR spectroscopy produces data suitable for metabolite profiling analysis of biofluids on a time scale that allows routine use. Extension of this approach to enhance the NMR detection of other classes of metabolites has also been accomplished. The improved detection of low-concentration metabolites shown here creates opportunities to improve the understanding of the biological processes and develop improved disease detection methodologies.

Original languageEnglish (US)
Pages (from-to)11540-11544
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number28
DOIs
StatePublished - Jul 10 2007

Keywords

  • Carbon-13
  • Inborn errors of metabolism
  • Metabolite profiling
  • Metabolomics metabonomics

ASJC Scopus subject areas

  • Genetics
  • General

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