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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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The impact of p53 on the urea cycle and nitrogen metabolism enzymes: Mechanisms and implications for cancer

Santhanagopalakrishnan Rajesh Iyer1, Beata Schlichtholz1

  • 1Department of Biochemistry, Medical University of Gdańsk, Poland.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|August 22, 2025
PubMed

Insights

The tumor suppressor protein p53 regulates nitrogen metabolism via the urea cycle, impacting cancer cell growth. Targeting urea cycle enzymes offers new cancer biomarkers and therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Metabolism

Background:

  • The tumor suppressor protein p53 (encoded by the TP53 gene) is crucial for genomic stability.
  • Its role in metabolic reprogramming, especially nitrogen metabolism, is increasingly recognized.
  • The urea cycle is vital for ammonia detoxification and biosynthesis.

Purpose of the Study:

  • To review the emerging role of p53 in nitrogen metabolism and the urea cycle.
  • To explore the implications of p53-mediated urea cycle regulation in cancer.
  • To propose urea cycle enzymes as potential cancer biomarkers and therapeutic targets.

Main Methods:

  • Literature review synthesizing current research on p53, nitrogen metabolism, and the urea cycle.
  • Analysis of p53's regulatory mechanisms on urea cycle enzymes.
  • Discussion of the role of urea cycle dysregulation in cancer.

Main Results:

  • p53 significantly influences nitrogen homeostasis by controlling urea cycle enzyme expression and activity.
  • This regulation impacts interconnected metabolic pathways (polyamine, methionine, glutathione, proline).
  • Cancer cells exploit urea cycle dysregulation to support their growth and survival.

Conclusions:

  • p53 plays a critical, underappreciated role in nitrogen metabolism.
  • Targeting urea cycle enzymes presents novel prognostic and therapeutic opportunities in oncology.
  • This research highlights nitrogen metabolism as a key area in cancer research and therapy.
Keywords:
Ammonia detoxificationCellular metabolic adaptationEnzyme regulationGlutathioneMethionine metabolismNitrogen metabolismPolyaminesUrea cyclep53

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