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Related Concept Videos

Urea Cycle01:23

Urea Cycle

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The urea cycle describes how liver cells convert ammonia to urea. Ammonia is a toxic waste product of protein catabolism. Land animals must convert ammonia into the less toxic urea which can be safely eliminated by the kidneys through urine. Marine animals excrete ammonia directly, and the surrounding water dilutes the ammonia to safe levels.
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Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
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Related Experiment Video

Updated: Apr 5, 2026

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
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Ammonia Detoxification Inhibits Liver Metastasis by Reshaping Hepatic Microenvironment.

Sumin Sun1,2,3, Haili Hu1,2,3, Long Chen1,3,4

  • 1Jiangsu Institute of Cancer Research, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 4, 2026
PubMed
Summary

Pathological ammonia accumulation in the liver promotes cancer metastasis by altering the microenvironment. The ammonia detoxifier L-ornithine-L-aspartate (LOLA) reduces liver metastasis in mouse models.

Keywords:
ammoniafibroblastsliver metastasismyeloidtumor microenvironment

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Area of Science:

  • Oncology
  • Metabolic pathways
  • Cancer microenvironment

Background:

  • Liver metastases are a significant unmet need in cancer therapy.
  • Dysregulated ammonia metabolism contributes to liver metastasis formation.

Purpose of the Study:

  • To investigate the role of pathological ammonia accumulation in promoting liver metastasis.
  • To explore L-ornithine-L-aspartate (LOLA) as a therapeutic strategy.

Main Methods:

  • Metabolomic and transcriptomic analyses.
  • Tumor microenvironmental profiling and single-cell RNA sequencing.
  • In vivo mouse models of liver metastasis.

Main Results:

  • Cancer cell metabolic reprogramming impairs the urea cycle, leading to ammonia accumulation.
  • Ammonia remodels the hepatic microenvironment by altering immune cells and fibroblasts.
  • LOLA treatment reduces ammonia levels, reshapes the microenvironment, and decreases metastatic burden.

Conclusions:

  • Pathological ammonia accumulation is crucial for establishing a pro-metastatic liver microenvironment.
  • LOLA is a promising therapeutic agent for liver metastasis by detoxifying ammonia.