Arginine is synthesized from proline, not glutamate, in enterally fed human preterm neonates

In neonatal mammals, arginine is synthesized in the enterocyte, with either proline or glutamate as the dietary precursor. We have shown several times in piglets that proline is the only precursor to arginine, although in vitro evidence supports glutamate in this role. Because of this uncertainty, we performed a multitracer stable isotope study to determine whether proline, glutamate, or both are dietary precursors for arginine in enterally fed human neonates. Labeled arginine (M + 2), proline (M + 1), and glutamate (M + 3) were given enterally to 15 stable, growing preterm infants (GA at birth 30-35 wk) at 1-3 wk postnatal age. Enrichment in urine of the tracer amino acids and the M + 1 and M + 3 isotopomers of arginine were measured by LC-tandem mass spectrometry to determine the contribution of proline and glutamate to arginine synthesis. Plateau enrichments of arginine and proline tracers were measurable in urine. Urinary glutamate enrichment was not detected. Conversion of proline to arginine was detected. However, the M + 3 isotopomer of arginine, which would have been synthesized from glutamate, was not detected. We conclude that, in contrast to the current consensus in the literature based on in vitro studies, proline is the major contributor to arginine synthesis in human preterm infants.