Glutamine Metabolism in Immune and Muscle Function

Glutamine stands as the most abundant amino acid in human plasma and tissues, serving both as a critical fuel and a nitrogen donor for rapidly proliferating cells. In the immune system, lymphocytes, macrophages and neutrophils rely heavily on glutamine to support nucleotide synthesis, cytokine production and reactive oxygen species management. During activation, these cells upregulate glutamine transport and metabolic enzymes to meet increased bioenergetic and biosynthetic demands. In skeletal muscle, glutamine acts as a key precursor for protein synthesis and interorgan nitrogen exchange. Under catabolic stress—such as prolonged exercise, trauma or infection—muscle tissue releases glutamine to sustain immune function and maintain acid–base balance. Dysregulation of glutamine homeostasis can impair immune competence, exacerbate muscle wasting and compromise recovery. A detailed understanding of glutamine’s role in signalling pathways, such as the mammalian target of rapamycin complex 1 (mTORC1), and its crosstalk with autophagy, is essential for the development of targeted nutritional and pharmacological interventions.

Research from Nature Portfolio

Recent studies have elucidated how autophagy and glutamine metabolism cooperate to reactivate mTORC1 under prolonged amino acid deprivation. By tracing glutamine conversion to glutamate and subsequent replenishment of non-essential amino acids, researchers have demonstrated that autophagy-derived substrates are indispensable for mTORC1 signalling and cell growth during starvation. Inhibition of key enzymes in glutaminolysis or blockage of autophagic flux disrupts this adaptive circuit, underscoring a specific metabolic programme in which glutamine availability directly governs nutrient-sensitive kinase activity and cell proliferation.

Glutamine Metabolism in Immune and Muscle Function publication trend

The graph below shows the total number of articles in glutamine metabolism in immune and muscle function across all publications each year (not limited to Nature Index journals).

Technical terms

Glutaminolysis: The catabolic conversion of glutamine into glutamate and downstream metabolites that feed into the tricarboxylic acid cycle.

Anaplerosis: The replenishment of tricarboxylic acid cycle intermediates through metabolic inputs such as glutamine-derived α-ketoglutarate.

mTORC1: A multiprotein kinase complex that senses amino acid availability, energy status and growth signals to regulate protein synthesis and autophagy.

Autophagy: A lysosome-mediated process by which cells degrade and recycle intracellular components to maintain nutrient homeostasis.

Immunonutrient: A dietary substance, such as glutamine, that modulates immune cell function and inflammatory responses.

References

1. Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation. Nature Communications (2017).
2. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients (2018).
3. Glutamine metabolism and optimal immune and CNS function.. Proceedings of The Nutrition Society (2022).