Analysis of glucose-derived amino acids involved in one-carbon and cancer metabolism by stable-isotope tracing gas chromatography mass spectrometry

Mark L. Sowers, Jason Herring, William Zhang, Hui Tang, Yang Ou, Wei Gu, Kangling Zhang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

A major hallmark of cancer is a perturbed metabolism resulting in high demand for various metabolites, glucose being the most well studied. While glucose can be converted into pyruvate for ATP production, the serine synthesis pathway (SSP) can divert glucose to generate serine, glycine, and methionine. In the process, the carbon unit from serine is incorporated into the one-carbon pool which makes methionine and maintains S-adenosylmethionine levels, which are needed to maintain the epigenetic landscape and ultimately controlling what genes are available for transcription. Alternatively, the carbon unit can be used for purine and thymidylate synthesis. We present here an approach to follow the flux through this pathway in cultured human cells using stable isotope enriched glucose and gas chromatography mass spectrometry analysis of serine, glycine, and methionine. We demonstrate that in three different cell lines this pathway contributes only 1–2% of total intracellular methionine. This suggests under high extracellular methionine conditions, the predominance of carbon units from this pathway are used to synthesize nucleic acids.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalAnalytical Biochemistry
Volume566
DOIs
StatePublished - Feb 1 2019

Keywords

  • Cancer metabolism
  • GC/MS
  • Glucose metabolism
  • Isotope traing mass spectrometry
  • One carbon metabolism
  • Serine metabolism
  • Warburg effect

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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