title: Arginine synthesis from enteral glutamine in healthy adults in the fed state.
abstract: Recent studies have documented transfer of labeled nitrogen from [2-(15)N]glutamine to citrulline and arginine in fasting human adults. Conversely, in neonates and piglets we have shown no synthesis of arginine from [2-(15)N]glutamate, and others have shown in mice that glutamine is a nitrogen, but not a carbon donor, for arginine synthesis. Therefore, we performed a multitracer study to determine whether glutamine is a nitrogen and/or carbon donor for arginine in healthy adult men. Two glutamine tracers, 2-(15)N and 1-(13)C, were given enterally to five healthy men fed a standardized milkshake diet. There was no difference in plasma enrichments between the two glutamine tracers. 1-(13)C isotopomers of citrulline and arginine were synthesized from [1-(13)C]glutamine. Three isotopomers each of citrulline and arginine were synthesized from the [2-(15)N]glutamine tracer: 2-(15)N, 5-(15)N, and 2,5-(15)N(2). Significantly greater enrichment was found of both [5-(15)N]arginine (0.75%) and citrulline (3.98%) compared with [2-(15)N]arginine (0.44%) and [2-(15)N]citrulline (2.62%), indicating the amino NH(2) from glutamine is mostly transferred to arginine and citrulline by transamination. Similarly, the enrichment of the 1-(13)C isotopomers was significantly less than the 2-(15)N isotopomers, suggesting rapid formation of α-ketoglutarate and recycling of the nitrogen label. Our results show that the carbon for 50% of newly synthesized arginine comes from dietary glutamine but that glutamine acts primarily as a nitrogen donor for arginine synthesis. Hence, studies using [2-(15)N]glutamine will overestimate arginine synthesis rates.
authors.affiliation: Division of Gastroenterology and Nutrition,Research Institute, The Hospital for Sick Children, University of Toronto, 555 University Ave., Toronto, Ontario, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Tomlinson
authors.forename: Mahroukh
authors.initials: M
authors.lastname: Rafii
authors.forename: Ronald O
authors.initials: RO
authors.lastname: Ball
authors.forename: Paul
authors.initials: P
authors.lastname: Pencharz
mesh_terms: D001120:Arginine / Q000096:biosynthesis* / Q000097:blood*; D002247:Carbon Isotopes; D002956:Citrulline / Q000096:biosynthesis / Q000097:blood; D004435:Eating / Q000502:physiology*; D018698:Glutamic Acid / Q000096:biosynthesis / Q000097:blood; D005973:Glutamine / Q000493:pharmacokinetics*; D006801:Humans; D007656:Ketoglutaric Acids / Q000097:blood; D008297:Male; D008954:Models, Biological; D009587:Nitrogen Isotopes; D009952:Ornithine / Q000096:biosynthesis / Q000097:blood; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D007656:Ketoglutaric Acids; D009587:Nitrogen Isotopes; D005973:Glutamine; D002956:Citrulline; D018698:Glutamic Acid; D001120:Arginine; D009952:Ornithine