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Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production.
Am J Clin Nutr 2009; 89(1):142-52AJ

Abstract

BACKGROUND

L-Arginine is an important precursor of nitric oxide (NO) and protein synthesis. Arginine is produced in the body (mainly kidney) by de novo production from citrulline and by protein breakdown. Arginine availability appears to be limited in sepsis.

OBJECTIVE

The objective was to compare arginine and citrulline metabolism in septic patients and nonseptic control patients in an intensive care unit (ICU) and in healthy control subjects.

DESIGN

Ten patients with septic shock, 7 critically ill control patients, and 16 healthy elderly subjects were studied. Metabolism was measured by using a primed continuous (2 h) stable-isotope infusion protocol. NO production was calculated as the conversion rate of arginine to citrulline; de novo arginine production was calculated as the conversion rate of citrulline to arginine. Arterial blood (arterialized venous blood in healthy subjects) was collected for the measurement of amino acid enrichment and concentrations. Data are reported as means +/- SDs.

RESULTS

Whole-body citrulline production was significantly lower in septic patients (4.5 +/- 2.1 micromol . kg(-1) . h(-1)) than in ICU control patients (10.1 +/- 2.9 micromol . kg(-1) . h(-1); P < 0.01) and in healthy control subjects (13.7 +/- 4.1 micromol . kg(-1) . h(-1); P < 0.001). Accordingly, de novo arginine production was lower in patients with sepsis (3.3 +/- 3.7 micromol . kg(-1) . h(-1)) than in healthy controls (11.9 +/- 6.6 micromol . kg(-1) . h(-1); P < 0.01) and tended to be lower in septic patients than in ICU control patients (10.9 +/- 9.4 micromol . kg(-1) . h(-1); P = 0.05). NO production was lower in septic patients than in healthy control subjects (P < 0.01), whereas a larger part of arginine was converted to urea in sepsis.

CONCLUSIONS

Citrulline production is severely low in patients with sepsis and is related to diminished de novo arginine and NO production. These metabolic alterations contribute to reduced citrulline and arginine availability, and these findings warrant further studies of therapeutic nutritional interventions to restore arginine metabolism in sepsis.

Authors+Show Affiliations

Center for Translational Research in Aging & Longevity, Donald W Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19056593

Citation

Luiking, Yvette C., et al. "Reduced Citrulline Production in Sepsis Is Related to Diminished De Novo Arginine and Nitric Oxide Production." The American Journal of Clinical Nutrition, vol. 89, no. 1, 2009, pp. 142-52.
Luiking YC, Poeze M, Ramsay G, et al. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009;89(1):142-52.
Luiking, Y. C., Poeze, M., Ramsay, G., & Deutz, N. E. (2009). Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. The American Journal of Clinical Nutrition, 89(1), pp. 142-52. doi:10.3945/ajcn.2007.25765.
Luiking YC, et al. Reduced Citrulline Production in Sepsis Is Related to Diminished De Novo Arginine and Nitric Oxide Production. Am J Clin Nutr. 2009;89(1):142-52. PubMed PMID: 19056593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. AU - Luiking,Yvette C, AU - Poeze,Martijn, AU - Ramsay,Graham, AU - Deutz,Nicolaas E P, Y1 - 2008/12/03/ PY - 2008/12/6/pubmed PY - 2009/2/6/medline PY - 2008/12/6/entrez SP - 142 EP - 52 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 89 IS - 1 N2 - BACKGROUND: L-Arginine is an important precursor of nitric oxide (NO) and protein synthesis. Arginine is produced in the body (mainly kidney) by de novo production from citrulline and by protein breakdown. Arginine availability appears to be limited in sepsis. OBJECTIVE: The objective was to compare arginine and citrulline metabolism in septic patients and nonseptic control patients in an intensive care unit (ICU) and in healthy control subjects. DESIGN: Ten patients with septic shock, 7 critically ill control patients, and 16 healthy elderly subjects were studied. Metabolism was measured by using a primed continuous (2 h) stable-isotope infusion protocol. NO production was calculated as the conversion rate of arginine to citrulline; de novo arginine production was calculated as the conversion rate of citrulline to arginine. Arterial blood (arterialized venous blood in healthy subjects) was collected for the measurement of amino acid enrichment and concentrations. Data are reported as means +/- SDs. RESULTS: Whole-body citrulline production was significantly lower in septic patients (4.5 +/- 2.1 micromol . kg(-1) . h(-1)) than in ICU control patients (10.1 +/- 2.9 micromol . kg(-1) . h(-1); P < 0.01) and in healthy control subjects (13.7 +/- 4.1 micromol . kg(-1) . h(-1); P < 0.001). Accordingly, de novo arginine production was lower in patients with sepsis (3.3 +/- 3.7 micromol . kg(-1) . h(-1)) than in healthy controls (11.9 +/- 6.6 micromol . kg(-1) . h(-1); P < 0.01) and tended to be lower in septic patients than in ICU control patients (10.9 +/- 9.4 micromol . kg(-1) . h(-1); P = 0.05). NO production was lower in septic patients than in healthy control subjects (P < 0.01), whereas a larger part of arginine was converted to urea in sepsis. CONCLUSIONS: Citrulline production is severely low in patients with sepsis and is related to diminished de novo arginine and NO production. These metabolic alterations contribute to reduced citrulline and arginine availability, and these findings warrant further studies of therapeutic nutritional interventions to restore arginine metabolism in sepsis. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/19056593/Reduced_citrulline_production_in_sepsis_is_related_to_diminished_de_novo_arginine_and_nitric_oxide_production_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.2007.25765 DB - PRIME DP - Unbound Medicine ER -