Arginine synthesis from enteral glutamine in healthy adults in the fed state

Tomlinson C, Rafii M, Ball RO, Pencharz P. Arginine synthesis from enteral glutamine in healthy adults in the fed state. Am J Physiol Endocrinol Metab 301: E267-E273, 2011. First published May 3, 2011; doi:10.1152/ajpendo.00006.2011.-Recent studies have documented transfer of labeled nitrogen from [2-N-15] glutamine to citrulline and arginine in fasting human adults. Conversely, in neonates and piglets we have shown no synthesis of arginine from [2-N-15] 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-N-15 and 1-C-13, 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-C-13 isotopomers of citrulline and arginine were synthesized from [1-C-13] glutamine. Three isotopomers each of citrulline and arginine were synthesized from the [2-N-15] glutamine tracer: 2-N-15, 5-N-15, and 2,5-N-15(2). Significantly greater enrichment was found of both [5-N-15] arginine (0.75%) and citrulline (3.98%) compared with [2-N-15] arginine (0.44%) and [2-N-15] citrulline (2.62%), indicating the amino NH2 from glutamine is mostly transferred to arginine and citrulline by transamination. Similarly, the enrichment of the 1-C-13 isotopomers was significantly less than the 2-N-15 isotopomers, suggesting rapid formation of alpha-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-N-15] glutamine will overestimate arginine synthesis rates.