Related Experiment Video
Updated: Jul 4, 2026
Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
Published on: December 16, 2021
Interorgan synthesis of arginine is down-regulated in tumor-bearing mice undergoing surgical trauma
Yvonne L J Vissers1, Maarten F von Meyenfeldt, Yvette C Luiking
1Department of Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Abstract:
Renal de novo arginine production has been suggested to be crucial for regulation of arginine production in disease. We investigated how the interorgan pathway for de novo arginine production is affected by the presence of malignant tumor and/or surgical trauma. Controls and methylcholanthrene-sarcoma-bearing mice were studied, both with and without undergoing laparotomy (n = 9-13 per group). One day after laparotomy, amino acid fluxes across the hindquarter, intestine, liver, and kidney were studied. In contrast to healthy mice, the liver of tumor-bearing mice took up citrulline (9 +/- 3 vs 1 +/- 2 nmol/[10 g min], P < .05), simultaneous with attenuated renal arginine output (4 +/- 3 vs 12 +/- 2 nmol/[10 g min], P < .05), despite increased intestinal conversion of glutamine to citrulline (15 +/- 3 vs 8 +/- 1 nmol/[10 g min], P < .05). In tumor-bearing mice undergoing surgery, intestinal citrulline output decreased (from 15 +/- 3 to 8 +/- 2 nmol/[10 g min], P < .05) and renal arginine output remained close to zero despite increased renal citrulline uptake (from 6 +/- 2 to 12 +/- 2 nmol/[10 g min], P < .05). In conclusion, the interorgan pathway for de novo arginine production was differently regulated depending on the pathophysiological situation. In methylcholanthrene-sarcoma-bearing mice, decreased de novo arginine production was accompanied by the presence of hepatic citrulline uptake, whereas tumor-bearing mice subjected to surgical trauma showed concomitant decreased intestinal citrulline output.
Insights
In disease, de novo arginine production is altered by tumors and surgery. The liver shifts to citrulline uptake, reducing kidney arginine output, especially after surgical trauma.
Area of Science:
- Biochemistry
- Physiology
- Oncology
Background:
- De novo arginine production in the kidney is vital for regulating arginine levels during disease.
- The impact of malignant tumors and surgical trauma on the interorgan pathway of de novo arginine production requires further investigation.
Purpose of the Study:
- To investigate how malignant tumors and surgical trauma affect the interorgan pathway for de novo arginine production.
- To understand the metabolic shifts in amino acid fluxes across major organs in response to these conditions.
Main Methods:
- Studied control and methylcholanthrene-sarcoma-bearing mice, with and without laparotomy.
- Analyzed amino acid fluxes across the hindquarter, intestine, liver, and kidney one day post-surgery.
- Utilized isotopic tracing to quantify metabolic pathways.
Main Results:
- Tumor-bearing mice showed hepatic citrulline uptake and reduced renal arginine output, contrasting with controls.
- Surgical trauma in tumor-bearing mice led to decreased intestinal citrulline output and near-zero renal arginine output despite increased renal citrulline uptake.
- Intestinal conversion of glutamine to citrulline increased in tumor-bearing mice but decreased with added surgical trauma.
Conclusions:
- The interorgan pathway for de novo arginine production is differentially regulated by pathological conditions.
- Hepatic citrulline uptake is associated with decreased de novo arginine production in tumor-bearing mice.
- Surgical trauma exacerbates metabolic dysregulation, significantly reducing intestinal citrulline output and renal arginine production.
