title: Kinetics of the utilization of dietary arginine for nitric oxide and urea synthesis: insight into the arginine-nitric oxide metabolic system in humans.
abstract: BACKGROUND
  The systemic availability of oral/dietary arginine and its utilization for nitric oxide (NO) synthesis remains unknown and may be related to a competitive hydrolysis of arginine into urea in the splanchnic area and systemic circulation.
  
  
  OBJECTIVE
  We investigated the kinetics and dose-dependency of dietary arginine utilization for NO compared with urea synthesis and studied the characteristics of the arginine-NO metabolic system in healthy humans.
  
  
  METHODS
  We traced the metabolic fate and analyzed the utilization dynamics of dietary arginine after its ingestion at 2 nutritional amounts in healthy humans (n = 9) in a crossover design by using [(15)N-(15)N-(guanido)]-arginine, isotope ratio mass spectrometry techniques, and data analysis with a compartmental modeling approach.
  
  
  RESULTS
  Whatever the amount of dietary arginine, 60 ± 3% (±SEM) was converted to urea, with kinetics indicative of a first-pass splanchnic phenomenon. Despite this dramatic extraction, intact dietary arginine made a major contribution to the postprandial increase in plasma arginine. However, the model identified that the plasma compartment was a very minor (~2%) precursor for the conversion of dietary arginine into NO, which, in any case, was small (<0.1% of the dose). The whole-body and plasma kinetics of arginine metabolism were consistent with the suggested competitive metabolism by the arginase and NO synthase pathways.
  
  
  CONCLUSIONS
  The conversion of oral/dietary arginine into NO is not limited by the systemic availability of arginine but by a tight metabolic compartmentation at the systemic level. We propose an organization of the arginine metabolic system that explains the daily maintenance of NO homeostasis in healthy humans.
authors.affiliation: UMR914 Nutrition Physiology and Ingestive Behavior CRNH-IdF, AgroParisTech, Paris, France. francois.mariotti@agroparistech.fr
authors.forename: François
authors.initials: F
authors.lastname: Mariotti
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Petzke
authors.forename: Damien
authors.initials: D
authors.lastname: Bonnet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Szezepanski
authors.forename: Cécile
authors.initials: C
authors.lastname: Bos
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Huneau
authors.forename: Hélène
authors.initials: H
authors.lastname: Fouillet
mesh_terms: D000293:Adolescent; D000328:Adult; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000097:blood / Q000493:pharmacokinetics*; D015992:Body Mass Index; D002852:Chromatography, Ion Exchange; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D008962:Models, Theoretical; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009587:Nitrogen Isotopes / Q000032:analysis; D019518:Postprandial Period; D014508:Urea / Q000097:blood* / Q000652:urine; D055815:Young Adult
chemical_list: D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D014508:Urea; D001120:Arginine; D003404:Creatinine; D019001:Nitric Oxide Synthase; D001119:Arginase