Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism
Open accessAbstract
Background The liver plays a central role in amino acid metabolism. However, because of limited accessibility of the portal vein, human data on this subject are scarce.Objective We studied hepatic amino acid metabolism in noncirrhotic fasting patients undergoing liver surgery.Design Twenty patients undergoing hepatectomy for colorectal metastases in a normal liver were studied. Before resection, blood was sampled from a radial artery, portal vein, hepatic vein, and renal vein. Organ blood flow was measured by duplex ultrasound scan.Results The intestine consumed glutamine and released citrulline. Citrulline was taken up by the kidney. This was accompanied by renal arginine release, which supports the view that glutamine is a precursor for arginine synthesis through an intestinal-renal pathway. The liver was found to extract citrulline from this pathway at a rate that was dependent on intestinal citrulline release (P < 0.0001) and hepatic citrulline influx (P = 0.03). Fractional hepatic extractions of citrulline (8.4%) and arginine (11.5%) were not significantly different. Eighty-eight percent of arginine reaching the liver passed it unchanged. Splanchnic citrulline release could account for one-third of renal citrulline uptake.Conclusions This is the first study of hepatic and interorgan amino acid metabolism in humans with a normal liver. The data indicate that glutamine is a precursor of ornithine, which can be converted to citrulline by the intestine; citrulline is transformed in the kidneys to arginine. Hepatic citrulline uptake limits the amount of gut-derived citrulline reaching the kidney. These findings may have implications for interventions aimed at increasing systemic arginine concentrations.
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Unlike arginine, citrulline catabolism is limited in the intestines as well as its extraction from hepatic tissue, resulting in the majority of citrulline passing into systemic circulation before conversion to arginine.
“Unlike arginine, citrulline catabolism is limited in the intestines [540] as well as its extraction from hepatic tissue [541] resulting in the majority of citrulline passing into systemic circulation before conversion to arginine [542].”
From ISSN exercise & sports nutrition review update: research & recommendations (2018) · cites this paper as [541]
The Discussion reports hepatic citrulline extraction of 8.4%, but says it was not significantly different from arginine extraction (11.5%). The ‘Citrulline exchange between the intestine and the liver’ section reports that net splanchnic release was only 45% of intestinal citrulline release. Thus, the paper supports some hepatic passage of citrulline, but not the implied contrast with arginine or the claim that most gut-derived citrulline reaches systemic circulation. (LLM, conf=0.84)
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- Authors
- van de Poll, M. C., Siroen, M. P., van Leeuwen, P. A., Soeters, P. B., Melis, G. C., Boelens, P. G., Deutz, N. E., & Dejong, C. H.
- Affiliations
- Maastricht University Medical Centre (NL)
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 85
- Issue
- 1
- Pages
- 167-172
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W1881669090
- Cited by
- 182
- References
- 34
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 12 · 2020: 12 · 2019: 9 · 2018: 4 · 2017: 15 · 2016: 10 · 2015: 10 · 2014: 9 · 2013: 12 · 2012: 9
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- arginine metabolism, citrulline metabolism, glutamine, hepatic amino acid metabolism, hepatectomy, colorectal cancer metastasis, fasting
- MeSH terms
- Adult, Aged, Arginine, Blood Flow Velocity, Citrulline, Female, Glutamine, Hepatectomy, Humans, Intestine, Small, Kidney, Liver, Male, Middle Aged, Organ Specificity, Ornithine, Colorectal Neoplasms
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