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Am J Physiol Endocrinol Metab (June 26, 2007). doi:10.1152/ajpendo.00290.2007
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Submitted on May 10, 2007
Accepted on June 20, 2007

A multi-tracer stable isotope quantification of the effects of arginine intake on whole-body arginine metabolism in neonatal piglets

Kristine L Urschel1, Mahroukh Rafii2, Paul B Pencharz3, and Ronald O. Ball4*

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

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

We have shown that deficient arginine intake increased the rate of endogenous arginine synthesis from proline. In this paper we report in vivo quantification of the effects of arginine intake on total arginine synthesis, the rates of conversion between arginine, citrulline, ornithine and proline, and on nitric oxide synthesis. Male piglets, with gastric catheters for diet and isotope infusion and femoral vein catheters for blood sampling, received a complete diet for 2 d, and then either a generous (+Arg; 1.80 g·kg-1·d-1; n = 5) or deficient (-Arg; 0.20 g·kg-1·d-1; n = 5) arginine diet for 5 d. On d 7, piglets received a primed, constant infusion of [guanido-15N2]arginine, [ureido-13C; 5,5-2H2]citrulline, [U-13C5]ornithine and [15N; U-13C5]proline in an integrated study of the metabolism of arginine and its precursors. Arginine synthesis ((µmol·kg-1·h-1) from both proline (+Arg: 42; -Arg: 74; pooled SE: 5) and citrulline (+Arg: 67; -Arg: 120; pooled SE: 15) were higher in piglets receiving the -Arg diet (P < 0.05); and for both diets proline accounted for ~60% of total arginine synthesis. The conversion of proline to citrulline (+Arg: 39; -Arg: 67; pooled SE: 6) was similar to the proline to arginine conversion, confirming that citrulline formation limits arginine synthesis from proline in piglets. Nitric oxide synthesis (µmol·kg-1·h-1), measured by the rate conversion of [guanido-15N2]arginine to [ureido-15N]citrulline, was greater in piglets receiving the +Arg diet (105) than the -Arg diet (46; pooled SE: 10) (P < 0.05). This multi-isotope method allowed many aspects of arginine metabolism to be quantified simultaneously.




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