Kheradmand · Metabolomics : Official journal of the Metabolomic Society 2026 · In vitro controlled laboratory experiment · n=?

Excess glutamine rewires endothelial cell metabolism.

Level 5 - mechanism / opinion, no new human data

In vitro laboratory study using cultured primary human cells.

PubMed 42631795 · doi:10.1007/s11306-026-02515-4 · record verified 2026-08-26

What was done

Primary human coronary artery endothelial cells were cultured across varying concentrations of glutamine under both normal and high-glucose conditions. Researchers quantified glutamine uptake and glutamate secretion using a bioanalyzer, measured cellular oxidative respiration using a Seahorse metabolic analyzer, and traced glutamine carbon incorporation into the tricarboxylic acid (TCA) cycle, amino acids, and antioxidant pathways via liquid chromatography-mass spectrometry.

What was found

The abstract reports directional findings without specific numerical values. Increasing extracellular glutamine increased cellular glutamine uptake, while glutamate secretion plateaued above 2 mM. Excess glutamine was primarily stored intracellularly and increased oxidative respiration, TCA cycle isotope enrichment, and carbon flux into glutathione, UDP-GlcNAc, and amino acids. Concurrently, total intracellular concentrations of succinate, unsaturated fatty acids, and one-carbon metabolism-related metabolites decreased.

Why it matters

These results show that high glutamine concentrations induce metabolic rewiring and selective metabolite depletion in endothelial cells, cautioning against uncritical glutamine supplementation in vascular disease research and standard cell culture protocols.

Limits

The study is restricted to an in vitro cell culture model and lacks in vivo validation or clinical vascular outcomes. The abstract provides no exact quantitative metrics, sample sizes (replicate numbers), or statistical significance values.

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