Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [13C]-Glycerate Probes

Jun Chen, Evan LaGue, Junjie Li, Chendong Yang, Edward P. Hackett, Manuel Mendoza, Jeffry R. Alger, Ralph J. DeBerardinis, Ian R. Corbin, Kelvin L. Billingsley, Jae Mo Park

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The interplay between glycolysis and gluconeogenesis is central to carbohydrate metabolism. Here, we describe novel methods to assess carbohydrate metabolism using [13C]-probes derived from glycerate, a molecule whose metabolic fate in mammals remains underexplored. Isotope-based studies were conducted via NMR and mass spectrometry analyses of freeze-clamped liver tissue extracts after [2,3-13C2]glycerate infusion. The ex vivo investigations were correlated with in vivo measurements using hyperpolarized [1-13C]glycerate. Application of [13C]glycerate to N-nitrosodiethylamine (DEN)-treated rats provided further assessments of intermediary carbohydrate metabolism in hepatocellular carcinoma. This method afforded direct analyses of control versus DEN tissues, and altered ratios of 13C metabolic products as well as unique glycolysis intermediates were observed in the DEN liver/tumor. Isotopomer studies showed increased glycerate uptake and altered carbohydrate metabolism in the DEN rats.

Original languageEnglish (US)
Pages (from-to)196-202
Number of pages7
JournalAnalysis and Sensing
Volume1
Issue number4
DOIs
StatePublished - Nov 2021

Keywords

  • NMR spectroscopy
  • glycerate
  • hepatocellular carcinoma
  • hyperpolarized C
  • metabolism

ASJC Scopus subject areas

  • Electrochemistry
  • Analytical Chemistry
  • Biochemistry
  • Spectroscopy

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