De novo synthesis is the main source of ornithine for citrulline production in neonatal pigs

Abstract

Citrulline is an amino acid synthesized in the gut and utilized for the synthesis of the conditionally essential amino acid arginine. Recently, the origin of the ornithine utilized for citrulline synthesis has become a matter of discussion. Multiple physiological factors may have contributed to the differences found among different researchers; one of these is the developmental stage of the subjects studied. To test the hypothesis that during the neonatal period de novo synthesis is the main source of ornithine for citrulline synthesis, neonatal piglets were infused intravenously or intragastrically with [U-(13)C(6)]arginine, [U-(13)C(5)]glutamine, or [U-(13)C(5)]proline during the fasted and fed periods. [ureido-(15)N]citrulline and [(2)H(2)]ornithine were infused intravenously for the entire infusion protocol. During fasting, plasma proline (13%) and ornithine (19%) were the main precursors for citrulline synthesis, whereas plasma arginine (62%) was the main precursor for plasma ornithine. During feeding, enteral (27%) and plasma (12%) proline were the main precursors for the ornithine utilized in the synthesis of citrulline, together with plasma ornithine (27%). Enteral proline and glutamine were utilized directly by the gut to produce ornithine utilized for citrulline synthesis. Arginine was not utilized by the gut, which is consistent with the lack of arginase activity in the neonate. Arginine, however, was the main source (47%) of plasma ornithine and in this way contributed to citrulline synthesis. In conclusion, during the neonatal period, the de novo pathway is the predominant source for the ornithine utilized in the synthesis of citrulline, and proline is the preferred precursor.

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

“…In addition, the colostrum whey proteins may provide a specific maturation and growth effect on the immature gut epithelium. It is noteworthy that the circulating levels of some amino acids associated with gut growth and immunity [citrulline, arginine, ornithine, glutamine (38,56)] were markedly elevated in the BC group. Elevated levels of the essential amino acid valine in BC pigs could be important for general body growth and maturation during the first postnatal weeks when amino acid requirements are particularly high, also for preterm infants (1).…”

Raw bovine milk improves gut responses to feeding relative to infant formula in preterm piglets

“…Plasma citrulline originates mainly from enterocytes with glutamine and proline being its precursors (3), the former providing ϳ80% of plasma citrulline in humans (10,52). In neonatal pigs, enteral proline is the main precursor for citrulline synthesis, followed by glutamine, on the basis of in vivo, isotopic kinetic measurements (25). The glutamine content of the IF diet was greater than that in BC, BM, and WMP diets, whereas the proline content was comparable among the four diets (Table 1).…”

Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways

“…Several studies show that OAT does not work in this way in the liver, allowing the conversion of excess Orn (generated from Arg in the urea cycle) into P5C [22]. However, it is noteworthy that in the small intestine, OAT works in the reverse direction (P5C → Orn) [196], likely due to its high OAT and low PCDH content [1]. Another study supports the hypothesis that ATP and NADPH can be used to reduce Glu to glutamate-γ-semi-aldehyde, which is subsequently aminated by OAT to yield Orn in the small intestine [197,198].…”