Precursors for ornithine and citrulline synthesis in neonatal pigs

Abstract

Citrulline (CIT) is an amino acid synthesized by gut and utilized for the synthesis of the conditionally essential amino acid arginine (ARG). In turn, the immediate precursor for CIT synthesis, ornithine (ORN), can originate from proline (PRO) and glutamine (GLN) via ornithine aminotransferase (OAT, i.e., de novo synthesis) or from ARG via arginase. To test the hypothesis that during the neonatal period de novo synthesis is the main source of ORN for CIT synthesis, neonatal pigs were infused iv or ig with [U‐13C6]ARG, [U‐13C5]GLN or [U‐13C5]PRO during the fasted and fed periods. (ureido)[15N]CIT and [D2]ORN were infused iv for the entire infusion protocol. During fasting plasma PRO (13%) and ORN (19%) were the main precursors for CIT synthesis, whereas plasma ARG (62%) was the main precursor for plasma ORN. During feeding enteral (27%) and plasma (12%) PRO were the main precursors for the ORN utilized in the synthesis of CIT, together with plasma ORN (27%). Enteral PRO and GLN were utilized directly by the gut to produce ORN utilized for CIT synthesis. ARG was not utilized by the gut, which is consistent with the lack of arginase activity in neonates. ARG, however, was the main source (47%) of plasma ORN and in this way contributed to CIT synthesis. During the neonatal period the directionality of OAT, together with the lack of arginase activity in the gut, determine that the de novo pathway is the main source of ORN for CIT production.