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Arginine synthesis is regulated by dietary arginine intake in the enterally fed neonatal piglet

¹Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G 2P5; ²The Research Institute, The Hospital for Sick Children, and the Departments of ³Paediatrics and ⁴Nutritional Science, University of Toronto, Toronto, Ontario, Canada M5G 1X8

Submitted 28 July 2003 ; accepted in final form 11 May 2004

Arginine is conditionally indispensable in the neonate, and its synthesis in the intestine is not sufficient to meet requirements. It is not known how neonatal endogenous arginine synthesis is regulated and the degree to which proline and glutamate are used as precursors. Primed, constant intraportal and intragastric infusions of L-[U-¹⁴C]proline and L-[3,4-³H]glutamate, and intragastric L-[guanido-¹⁴C]arginine were used to measure whole body and first-pass intestinal arginine synthesis in 10 neonatal piglets fed generous (1.80 g·kg^–1·day^–1) or deficient (0.20 g·kg^–1·day^–1) quantities of arginine for 5 days. Glutamate tracer was not detected in arginine, indicating a biologically insignificant conversion of <1% of arginine flux. Endogenous arginine synthesis from proline had obligatory (0.36 g·kg^–1·day^–1) and maximal (0.68 g·kg^–1·day^–1) levels (P < 0.05, pooled SE 0.05). Although first-pass gut metabolism is responsible for 42–63% of whole body arginine synthesis, the gut is incapable of upregulating proline to arginine conversion during arginine deficiency, compared with a more than threefold increase without first-pass gut metabolism. These data suggest that upregulation of proline-to-arginine conversion occurs via increased arterial extraction of proline by the gut or in nonintestinal tissues. This study demonstrates that dietary arginine is an important regulator of endogenous arginine synthesis in the neonatal piglet and that proline, but not glutamate, is an important precursor for arginine synthesis in the neonate.

proline; glutamate; arginine requirement; biosynthesis; amino acid kinetics; first-pass metabolism

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