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

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.

LanguageEnglish (US)
Pages1-9
Number of pages9
JournalAnalytical Biochemistry
Volume566
DOIs
StatePublished - Feb 1 2019

Fingerprint

Metabolism
Isotopes
Gas chromatography
Methionine
Gas Chromatography-Mass Spectrometry
Mass spectrometry
Carbon
Serine
Amino Acids
Glucose
Neoplasms
Glycine
Cells
S-Adenosylmethionine
Transcription
Metabolites
Pyruvic Acid
Epigenomics
Nucleic Acids
Cultured Cells

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

Cite this

Analysis of glucose-derived amino acids involved in one-carbon and cancer metabolism by stable-isotope tracing gas chromatography mass spectrometry. / Sowers, Mark L.; Herring, Jason; Zhang, William; Tang, Hui; Ou, Yang; Gu, Wei; Zhang, Kangling.

In: Analytical Biochemistry, Vol. 566, 01.02.2019, p. 1-9.

Research output: Contribution to journalArticle

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