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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Citrulline Is an Effective Arginine Precursor in Enterally Fed Neonatal Piglets^1,2

Kristine L. Urschel^*, Anna K. Shoveller^*,3, Richard R. E. Uwiera, Paul B. Pencharz^*,**,, and Ronald O. Ball^*,**,,4

^* Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada T6G 2P5; Health Sciences and Laboratory Animal Services, University of Alberta, Edmonton AB, Canada T6G 2S2; ^** The Research Institute, The Hospital for Sick Children, Toronto, and the Departments of Paediatrics and Nutritional Science, University of Toronto, Toronto, ON, Canada M5G 1X8

⁴ To whom correspondence should be addressed. E-mail: ron.ball{at}ualberta.ca.

Although neonatal piglets can synthesize some arginine from proline, there is a limit to this synthesis, and piglets fed an arginine-deficient diet have diminished whole-body arginine status. To help elucidate where the limitation in arginine synthesis may occur, our objective was to determine the most effective arginine precursor in 1-wk-old enterally fed piglets. Piglets were administered either an arginine-deficient (basal) diet [1.15 mmol arginine/(kg·d)] or the basal diet supplemented with equimolar [9.18 mmol/(kg·d)] amounts of proline (+Pro), ornithine (+Orn), citrulline (+Cit) or arginine (+Arg) for 5 d (n = 5/diet). Daily blood samples were taken and indicators of whole-body arginine status including plasma amino acid, ammonia, and urea concentrations were measured. A primed, constant intragastric (i.g.) infusion of L-[U-¹⁴C]proline was given to measure the proline to arginine conversion, and intravenous (i.v.) and i.g. infusions of L-[guanido-¹⁴C]arginine were given to determine arginine flux and to quantify the splanchnic extraction of dietary arginine. Piglets fed the +Cit and +Arg diets had lower plasma ammonia and urea concentrations (P < 0.05) and higher plasma arginine concentrations (P < 0.0001) and arginine fluxes (P < 0.05) than piglets fed the other 3 diets. Piglets fed +Cit and +Arg had a lower proline to arginine conversion (P < 0.05). During first-pass splanchnic metabolism, 52% of the dietary arginine was extracted, and this extraction was not affected by whole-body arginine status (P > 0.05). These data indicate that citrulline, but not ornithine or proline, is an effective arginine precursor, and that either citrulline formation or availability appears to limit arginine synthesis in neonatal piglets.

KEY WORDS: • arginine biosynthesis • citrulline • first-pass splanchnic metabolism

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