ArticleAmerican journal of physiology. Renal physiology2014
Extrarenal citrulline disposal in mice with impaired renal function.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- L-Citrulline: Novel Pharmacotherapy to Improve Outcomes in Infants and Children at Risk of Systemic or Pulmonary Vascular Disease.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps.Clinical kidney journal · 2026Review
- Molecular mechanisms and therapies for tumor inhibition through the arginine metabolism pathway.Frontiers in oncology · 2026Review
- Impacts of conditionally essential amino acids, cysteine, and tyrosine on intestinal inflammation in celiac disease.Amino acids · 2025Review
- Pegylated arginine deiminase depletes plasma arginine but maintains tissue arginine availability in young pigs.American journal of physiology. Endocrinology and metabolism · 2021Article
- Arginine recycling in endothelial cells is regulated BY HSP90 and the ubiquitin proteasome system.Nitric oxide : biology and chemistry · 2021Article
- Arginase II Plays a Central Role in the Sexual Dimorphism of Arginine Metabolism in C57BL/6 Mice.The Journal of nutrition · 2020Article
- Developmental changes in the utilization of citrulline by neonatal pigs.American journal of physiology. Renal physiology · 2020Article
- Citrulline Generation Test: What Does It Measure?JPEN. Journal of parenteral and enteral nutrition · 2019Article
- The Citrulline Recycling Pathway Sustains Cardiovascular Function in Arginine-Depleted Healthy Mice, but Cannot Sustain Nitric Oxide Production during Endotoxin Challenge.The Journal of nutrition · 2018Article
- The construction of a panel of serum amino acids for the identification of early chronic kidney disease patients.Journal of clinical laboratory analysis · 2018Article
- Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice.The Journal of nutrition · 2017Article
- Vitamin E in New-Generation Lipid Emulsions Protects Against Parenteral Nutrition-Associated Liver Disease in Parenteral Nutrition-Fed Preterm Pigs.JPEN. Journal of parenteral and enteral nutrition · 2016Article
- Interrelationships between glutamine and citrulline metabolism.Current opinion in clinical nutrition and metabolic care · 2016Review
- Dietary arginine requirements for growth are dependent on the rate of citrulline production in mice.The Journal of nutrition · 2015Article
- Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice.PloS one · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal, it only accounts for ~60-70% of the citrulline produced. Because the only known fate for citrulline is arginine synthesis and the enzymes that catalyze this reaction are widespread among body tissues, we hypothesized that citrulline can be utilized directly by tissues to meet, at least partially, their arginine needs. To test this hypothesis, we used stable and radioactive tracers in conscious, partially nephrectomized (½ and ⅚) and anesthetized acutely kidney-ligated mouse models. Nephrectomy increased plasma citrulline concentration but did not affect citrulline synthesis rates, thus reducing its clearance. Nephrectomy (⅚) reduced the amount of citrulline accounted for as plasma arginine from 88 to 42%. Acute kidney ligation increased the half-life and mean retention time of citrulline. Whereas the rate of citrulline conversion into plasma arginine was reduced, it was not eliminated. In addition, we observed direct utilization of citrulline for arginine synthesis and further incorporation into tissue protein in kidney-ligated mice. These observations indicate that a fraction of the citrulline produced is utilized directly by multiple tissues to meet their arginine needs and that extrarenal sites contribute to plasma arginine. Furthermore, when the interorgan synthesis of arginine is impaired, these extrarenal sites are able to increase their rate of citrulline utilization.
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