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1 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
2 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada; The Research Institute, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada
3 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada; The Research Institute, The Hospital for Sick Children, Toronto, ON, Canada; Department of Nutritional Science, University of Toronto, Toronto, ON, Canada
* To whom correspondence should be addressed. E-mail: ron.ball{at}ualberta.ca.
Arginine is conditionally indispensable in the neonate and its synthesis in the intestine is not sufficient to meet requirement. 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.d-1) or deficient (0.20 g.kg-1.d-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.d-1), and maximal (0.68 g.kg-1.d-1) levels (P < 0.05, pooled SEM, 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 to a >3-fold 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 non-intestinal tissues. This study demonstrated 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.
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