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Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator?
Crit Care Med 2007; 35(9 Suppl):S568-76CC

Abstract

OBJECTIVE

Glutamine and arginine are both used as nutritional supplements in critically ill patients. Although glutamine has been shown to be beneficial for the metabolically stressed patient, considerations about arginine supplementation are not unanimously determined. Our aim is to review the current knowledge on the possible interplay between glutamine and arginine generation in the stressed patient and to elaborate on whether these amino acids may function as a common denominator. Because glutamine can be given by the parenteral and enteral routes, possible different actions on the metabolic fate (e.g., generation of citrulline) with both routes are analyzed.

DATA SOURCE

A summary of data on the clinical effect of glutamine and arginine metabolism is given, incorporating data on glutamine and arginine supplementation. Differences between the route of administration, parenteral or enteral, and the molecular form of supplied glutamine, free or as dipeptide, on citrulline generation by the gut and production of arginine are discussed.

RESULTS

Glutamine and arginine influence similar organ systems; however, they differ in their targets. For example, glutamine serves as fuel for the immune cells, increases human leukocyte antigen-DR expression on monocytes, enhances neutrophil phagocytosis, and increases heat shock protein expression. Arginine affects the immune system by stimulating direct or indirect proliferation of immune cells. This indirect effect is possibly mediated by nitric oxide, which also enhances macrophage cytotoxicity. Furthermore, glutamine serves as a precursor for the de novo production of arginine through the citrulline-arginine pathway. Glutamine has shown to be beneficial in the surgical and critically ill patient, whereas arginine supplementation is still under debate. The route of glutamine administration (parenteral or enteral) determines the effect on citrulline and on the de novo arginine generation. There is a marked difference between the administration of free glutamine and dipeptide enterally or parenterally. Splanchnic extraction of the hydrolyzed glutamine in mice when administering the dipeptide enterally is higher compared with administering free glutamine from the enteral site. In patients, splanchnic extraction of the dipeptide given enterally is 100% when comparing supplementation of the dipeptide intravenously.

CONCLUSIONS

The beneficial effects of free glutamine or dipeptide may depend on the route of administration but also on the metabolic fate of amino acids generated (e.g., citrulline, arginine). Glutamine serves as a substrate for de novo citrulline and arginine synthesis. More research needs to be done to establish the direct clinical relevance of the different metabolic pathways. Future perspectives might include combining enteral and parenteral routes of administrating free glutamine or dipeptide.

Authors+Show Affiliations

Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17713411

Citation

Vermeulen, Mechteld A R., et al. "Specific Amino Acids in the Critically Ill Patient--exogenous Glutamine/arginine: a Common Denominator?" Critical Care Medicine, vol. 35, no. 9 Suppl, 2007, pp. S568-76.
Vermeulen MA, van de Poll MC, Ligthart-Melis GC, et al. Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator? Crit Care Med. 2007;35(9 Suppl):S568-76.
Vermeulen, M. A., van de Poll, M. C., Ligthart-Melis, G. C., Dejong, C. H., van den Tol, M. P., Boelens, P. G., & van Leeuwen, P. A. (2007). Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator? Critical Care Medicine, 35(9 Suppl), pp. S568-76.
Vermeulen MA, et al. Specific Amino Acids in the Critically Ill Patient--exogenous Glutamine/arginine: a Common Denominator. Crit Care Med. 2007;35(9 Suppl):S568-76. PubMed PMID: 17713411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific amino acids in the critically ill patient--exogenous glutamine/arginine: a common denominator? AU - Vermeulen,Mechteld A R, AU - van de Poll,Marcel C G, AU - Ligthart-Melis,Gerdien C, AU - Dejong,Cornelis H C, AU - van den Tol,M Petrousjka, AU - Boelens,Petra G, AU - van Leeuwen,Paul A M, PY - 2007/9/22/pubmed PY - 2007/11/7/medline PY - 2007/9/22/entrez SP - S568 EP - 76 JF - Critical care medicine JO - Crit. Care Med. VL - 35 IS - 9 Suppl N2 - OBJECTIVE: Glutamine and arginine are both used as nutritional supplements in critically ill patients. Although glutamine has been shown to be beneficial for the metabolically stressed patient, considerations about arginine supplementation are not unanimously determined. Our aim is to review the current knowledge on the possible interplay between glutamine and arginine generation in the stressed patient and to elaborate on whether these amino acids may function as a common denominator. Because glutamine can be given by the parenteral and enteral routes, possible different actions on the metabolic fate (e.g., generation of citrulline) with both routes are analyzed. DATA SOURCE: A summary of data on the clinical effect of glutamine and arginine metabolism is given, incorporating data on glutamine and arginine supplementation. Differences between the route of administration, parenteral or enteral, and the molecular form of supplied glutamine, free or as dipeptide, on citrulline generation by the gut and production of arginine are discussed. RESULTS: Glutamine and arginine influence similar organ systems; however, they differ in their targets. For example, glutamine serves as fuel for the immune cells, increases human leukocyte antigen-DR expression on monocytes, enhances neutrophil phagocytosis, and increases heat shock protein expression. Arginine affects the immune system by stimulating direct or indirect proliferation of immune cells. This indirect effect is possibly mediated by nitric oxide, which also enhances macrophage cytotoxicity. Furthermore, glutamine serves as a precursor for the de novo production of arginine through the citrulline-arginine pathway. Glutamine has shown to be beneficial in the surgical and critically ill patient, whereas arginine supplementation is still under debate. The route of glutamine administration (parenteral or enteral) determines the effect on citrulline and on the de novo arginine generation. There is a marked difference between the administration of free glutamine and dipeptide enterally or parenterally. Splanchnic extraction of the hydrolyzed glutamine in mice when administering the dipeptide enterally is higher compared with administering free glutamine from the enteral site. In patients, splanchnic extraction of the dipeptide given enterally is 100% when comparing supplementation of the dipeptide intravenously. CONCLUSIONS: The beneficial effects of free glutamine or dipeptide may depend on the route of administration but also on the metabolic fate of amino acids generated (e.g., citrulline, arginine). Glutamine serves as a substrate for de novo citrulline and arginine synthesis. More research needs to be done to establish the direct clinical relevance of the different metabolic pathways. Future perspectives might include combining enteral and parenteral routes of administrating free glutamine or dipeptide. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/17713411/Specific_amino_acids_in_the_critically_ill_patient__exogenous_glutamine/arginine:_a_common_denominator L2 - http://Insights.ovid.com/pubmed?pmid=17713411 DB - PRIME DP - Unbound Medicine ER -