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Updated: Jul 12, 2026
Untargeted Metabolomics from Biological Sources Using Ultraperformance Liquid Chromatography-High Resolution Mass Spectrometry UPLC-HRMS
Published on: May 20, 2013
A targeted metabolomic method to detect epigenetically relevant metabolites.
Joan Miro-Blanch1, Alexandra Junza1, Jordi Capellades2
1Universitat Rovira i Virgili, Department of Electronic Engineering, 43007, Tarragona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain.
We developed a new method to measure over 30 epigenetically relevant metabolites, including short-chain fatty acids (SCFAs), and used stable isotope tracing to track key molecules like S-adenosylmethionine (SAM) and acetyl-CoA.
Area of Science:
- Metabolomics and Epigenetics
- Analytical Chemistry
- Biochemistry
Background:
- Epigenetic modifications are crucial in regulating gene expression and are influenced by cellular metabolism.
- Understanding the interplay between metabolites and epigenetic processes requires sensitive and versatile analytical methods.
- Key metabolic donors, S-adenosylmethionine (SAM) and acetyl-CoA, are central to methylation and acetylation, respectively.
Purpose of the Study:
- To create a sensitive analytical method for simultaneous detection of epigenetically relevant metabolites without derivatization.
- To establish stable isotope tracing to track the biosynthesis of SAM and acetyl-CoA.
- To demonstrate the method's accuracy and reproducibility in linking metabolism to epigenetics.
Main Methods:
- Developed a targeted metabolomics approach to quantify over 30 metabolites, including short-chain fatty acids (SCFAs), SAM, and acetyl-CoA.
- Employed a biphasic extraction followed by GC-MS/MS and LC-MS/MS for comprehensive metabolite analysis.
- Implemented stable isotope tracing using 13C-labeled nutrients to track carbon flow into SAM and acetyl-CoA.
Main Results:
- Successfully quantified over 30 epigenetically relevant metabolites with high reproducibility and sensitivity in biological samples.
- Observed significant differences in SCFA levels between germ-free and conventional mice, linking gut microbiota to metabolism.
- Demonstrated that vitamin B12 enhances OSKM reprogramming by increasing SAM labeling from 13C-serine and identified differential acetyl-CoA labeling in IDH1-mutant glioma cells.
Conclusions:
- The developed analytical method enables simultaneous quantification of key epigenetic metabolites and their precursors.
- Stable isotope tracing provides novel insights into metabolic pathways supporting epigenetic modifications, including glycolysis, folate, and methionine cycles.
- This approach facilitates integrative multi-omics studies to explore metabolism-epigenetics interplay in diverse biological contexts and diseases.
