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Detection of Localized Hepatocellular Amino Acid Kinetics by using Mass Spectrometry Imaging of Stable Isotopes
Author(s) -
Arts Martijn,
Soons Zita,
Ellis Shane R.,
Pierzchalski Keely A.,
Balluff Benjamin,
Eijkel Gert B.,
Dubois Ludwig J.,
Lieuwes Natasja G.,
Agten Stijn M.,
Hackeng Tilman M.,
van Loon Luc J. C.,
Heeren Ron M. A.,
Olde Damink Steven W. M.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702669
Subject(s) - phenylalanine , amino acid , chemistry , mass spectrometry , in vivo , mass spectrometry imaging , hydroxylation , metabolism , tyrosine , stable isotope labeling by amino acids in cell culture , ex vivo , biochemistry , isotope , isotope dilution , chromatography , biology , in vitro , proteomics , enzyme , physics , quantum mechanics , microbiology and biotechnology , gene
Mass spectrometry imaging (MSI) simultaneously detects and identifies the spatial distribution of numerous molecules throughout tissues. Currently, MSI is limited to providing a static and ex vivo snapshot of highly dynamic systems in which molecules are constantly synthesized and consumed. Herein, we demonstrate an innovative MSI methodology to study dynamic molecular changes of amino acids within biological tissues by measuring the dilution and conversion of stable isotopes in a mouse model. We evaluate the method specifically on hepatocellular metabolism of the essential amino acid l ‐phenylalanine, associated with liver diseases. Crucially, the method reveals the localized dynamics of l ‐phenylalanine metabolism, including its in vivo hydroxylation to l ‐tyrosine and co‐localization with other liver metabolites in a time course of samples from different animals. This method thus enables the dynamics of localized biochemical synthesis to be studied directly from biological tissues.