2‐ 15N Glutamine tracer overestimate rates of Arginine and Citrulline synthesis in healthy adult men

Abstract

Recent studies have documented transfer of labeled nitrogen from 2–15N glutamine (Gln) to citrulline (Cit) and arginine (Arg) in fasting human adults. Conversely, in neonates we have shown no synthesis of Arg from glutamate. Therefore, we performed a multitracer study with 2‐15N and 1‐13C Gln given enterally to 5 healthy men fed a standardized milkshake diet. There was no difference in plasma enrichments between the two Gln tracers. 1‐13C isomers of Cit and Arg were synthesized from 1‐13C Gln. Three isomers each of Cit and Arg were synthesized from the 2‐15N Gln tracer; 2‐15N, 5‐15N and 2,5 15N2. The enrichments of these isomers of Cit and Arg expressed as atom percent excess are shown in the table. Enrichment of Arg and Cit isomers synthesized from 1‐13C and 2‐15N Gln 1–13C 2–15N 5–15N 2,5–15N Cit (%) 1.41 2.61,2 4.02 0.8 Arg (%) 0.141 0.41 0.8 0.1 Significantly greater enrichment was found of both 5‐15N Arg and Cit compared to 2‐15N isomers2, indicating the amino N from Gln is mostly transferred to Arg and Cit by transamination. Similarly, the enrichment of the 1‐13C isomers was significantly less than the 2‐15N isomers 1 suggesting rapid formation of α‐ketoglutarate and recycling of the nitrogen label. Our results show Gln is acting primarily as a nitrogen donor for Arg synthesis and studies using 15N label overestimate Arg synthesis rates.Grant Funding Source: CIHR