title: Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study.
abstract: BACKGROUND
  Arginine plays a role in many different pathways in multiple cell types. Consequently, a shortage of arginine, caused by pathologic conditions such as cancer or injury, has the potential to disturb many cellular and organ functions. Glutamine is the ultimate source for de novo synthesis of arginine in humans via the intestinal-renal axis. Therefore, we hypothesized that parenteral glutamine supplementation may stimulate the interorgan pathway of arginine production.
  
  
  OBJECTIVE
  The objectives were to quantify arginine production from its precursor glutamine and to establish the contribution of the kidneys to de novo synthesis of arginine in patients receiving intravenous supplementation of glutamine dipeptide during major abdominal surgery.
  
  
  METHODS
  Whole-body and renal metabolism of glutamine, citrulline, and arginine was assessed by stable isotope techniques in 7 patients receiving a perioperative supplement of intravenous alanyl-glutamine (0.5 g · kg(-1) · d(-1)).
  
  
  RESULTS
  Plasma glutamine, citrulline, and arginine concentrations increased significantly in patients receiving intravenous glutamine dipeptide. At whole-body level, 91% of total citrulline turnover was derived from glutamine, whereas 49% of whole-body citrulline turnover was used for de novo synthesis of arginine. The kidneys were responsible for 75% of whole-body arginine production from citrulline.
  
  
  CONCLUSIONS
  Glutamine and citrulline are important sources for de novo arginine synthesis. The kidneys are the main production site for endogenous arginine. After comparison of these results with previous similar studies, our data suggest that an intravenous glutamine supplement doubles renal arginine production from citrulline. This trial was registered at www.trialregister.nl as NTR2914.
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Nikki
authors.initials: N
authors.lastname: Buijs
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Saskia J H
authors.initials: SJ
authors.lastname: Brinkmann
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: J Efraim
authors.initials: JE
authors.lastname: Oosterink
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Joanna
authors.initials: J
authors.lastname: Luttikhold
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Henk
authors.initials: H
authors.lastname: Schierbeek
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Willem
authors.initials: W
authors.lastname: Wisselink
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Albertus
authors.initials: A
authors.lastname: Beishuizen
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Johannes B
authors.initials: JB
authors.lastname: van Goudoever
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Alexander P J
authors.initials: AP
authors.lastname: Houdijk
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.affiliation: From the Departments of Surgery (NB, SJHB, JL, WW, and PAMvL), Internal Medicine (MARV), Intensive Care (AB), and Pediatrics (JBvG), VU University Medical Center, Amsterdam, Netherlands; the Department of Surgery, Medical Center Alkmaar, Trial Center Holland Health, Alkmaar, Netherlands (NB and APJH); the Department of Pediatrics, Academic Medical Center, Emma Children's Hospital, Amsterdam, Netherlands (JEO, HS, and JBvG); and the Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands (AB).
authors.forename: Mechteld A R
authors.initials: MA
authors.lastname: Vermeulen
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D001120:Arginine / Q000096:biosynthesis*; D002956:Citrulline / Q000378:metabolism; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004151:Dipeptides / Q000008:administration & dosage*; D005069:Evaluation Studies as Topic; D005260:Female; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D004151:Dipeptides; D005973:Glutamine; D002956:Citrulline; D001120:Arginine; C054122:alanylglutamine