Arginine: At the crossroads of nitrogen metabolism Review


Authors: Fung, T. S.; Ryu, K. W.; Thompson, C. B.
Review Title: Arginine: At the crossroads of nitrogen metabolism
Abstract: L-arginine is the most nitrogen-rich amino acid, acting as a key precursor for the synthesis of nitrogen-containing metabolites and an essential intermediate in the clearance of excess nitrogen. Arginine’s side chain possesses a guanidino group which has unique biochemical properties, and plays a primary role in nitrogen excretion (urea), cellular signaling (nitric oxide) and energy buffering (phosphocreatine). The post-translational modification of protein-incorporated arginine by guanidino-group methylation also contributes to epigenetic gene control. Most human cells do not synthesize sufficient arginine to meet demand and are dependent on exogenous arginine. Thus, dietary arginine plays an important role in maintaining health, particularly upon physiologic stress. How cells adapt to changes in extracellular arginine availability is unclear, mostly because nearly all tissue culture media are supplemented with supraphysiologic levels of arginine. Evidence is emerging that arginine-deficiency can influence disease progression. Here, we review new insights into the importance of arginine as a metabolite, emphasizing the central role of mitochondria in arginine synthesis/catabolism and the recent discovery that arginine can act as a signaling molecule regulating gene expression and organelle dynamics. © The Author(s) 2025.
Keywords: signal transduction; controlled study; human cell; review; nonhuman; animal; metabolism; animals; gene expression; protein processing; protein processing, post-translational; protein synthesis; gene control; amino acid; mitochondria; mitochondrion; metabolite; cell organelle; nitrogen; arginine; pharmacology; catabolism; urea; creatine phosphate; nitrogen metabolism; humans; human; arginine deficiency; arginine metabolism; metabolite signaling; tissue culture medium; nitrogen urine level
Journal Title: EMBO Journal
Volume: 44
Issue: 5
ISSN: 0261-4189
Publisher: Wiley Blackwell  
Date Published: 2025-03-03
Start Page: 1275
End Page: 1293
Language: English
DOI: 10.1038/s44318-025-00379-3
PUBMED: 39920310
PROVIDER: scopus
PMCID: PMC11876448
DOI/URL:
Notes: Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Craig Thompson -- Source: Scopus
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MSK Authors
  1. Craig Bernie Thompson
    155 Thompson
  2. Keunwoo Ryu
    6 Ryu
  3. Tak Shun Fung
    3 Fung