Glutamine reliance in cell metabolism.

TLDR: This review introduces the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamines metabolism to explain why cells exhibit metabolic reliance on glutamine and proposes a metabolic target for therapeutic intervention in cancer.

Abstract: As knowledge of cell metabolism has advanced, glutamine has been considered an important amino acid that supplies carbon and nitrogen to fuel biosynthesis. A recent study provided a new perspective on mitochondrial glutamine metabolism, offering mechanistic insights into metabolic adaptation during tumor hypoxia, the emergence of drug resistance, and glutaminolysis-induced metabolic reprogramming and presenting metabolic strategies to target glutamine metabolism in cancer cells. In this review, we introduce the various biosynthetic and bioenergetic roles of glutamine based on the compartmentalization of glutamine metabolism to explain why cells exhibit metabolic reliance on glutamine. Additionally, we examined whether glutamine derivatives contribute to epigenetic regulation associated with tumorigenesis. In addition, in discussing glutamine transporters, we propose a metabolic target for therapeutic intervention in cancer. Insights into how the amino acid glutamine powers cellular metabolism could pave the way for effective therapeutic strategies for ‘starving’ tumor cells. Healthy cells can manufacture enough glutamine to sustain normal function, but cancerous growth creates heavier demand for this important molecule. Jung Min Han and colleagues at Yonsei University in Incheon, South Korea have reviewed the various cellular functions of glutamine, and discuss opportunities to cut off supply and thereby derail tumor proliferation. Glutamine serves as a building block both for amino acids and nucleic acids, and is also consumed during mitochondrial energy production. Several groups are exploring the feasibility of inactivating glutamine synthesis or halting cellular uptake of this amino acid as a means of depriving cancer cells of nutrients. A deeper understanding of glutamine’s metabolic functions should accelerate progress on this front.