Detection of Localized Hepatocellular Amino Acid Kinetics by Using Mass Spectrometry Imaging of Stable Isotopes

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2017 May 12

PMID 28493648

Citations 12

Authors

Martijn Arts

Zita Soons

Shane R Ellis

Keely A Pierzchalski

Benjamin Balluff

Gert B Eijkel

Ludwig J Dubois

Natasja G Lieuwes

Stijn M Agten

Tilman M Hackeng

Luc J C van Loon

Ron M A Heeren

Steven W M Olde Damink

Affiliations

Soon will be listed here.

Abstract

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.

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