Developmental changes in the utilization of citrulline by neonatal pigs

Authors: MOHAMMAD, MAHMOUD - Children'S Nutrition Research Center (CNRC); DIDELIJA, INKA - Children'S Nutrition Research Center (CNRC); WANG, XIOYING - Children'S Nutrition Research Center (CNRC); STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); Burrin, Douglas - Doug; MARINI, JUAN - Children'S Nutrition Research Center (CNRC)

Submitted to: American Journal of Physiology - Renal Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2019
Publication Date: 11/25/2019
Citation: Mohammad, M., Didelija, I., Wang, X., Stoll, B., Burrin, D.G., Marini, J. 2019. Developmental changes in the utilization of citrulline by neonatal pigs. American Journal of Physiology - Renal Physiology. https://doi.org/doi:10.1152/ajprenal.00469.2019.
DOI: https://doi.org/10.1152/ajprenal.00469.2019

Interpretive Summary: The genetic expression of the enzymes that make the amino acid arginine in the kidney is lower in neonates and for this reason it is believe that neonates have a limited capacity to make arginine. By giving a dose of citrulline, the precursor for arginine synthesis, we were able to determine its utilization. We confirmed that in preterm and term pigs at birth the ability to utilize citrulline for arginine production is lower than in one week old animals. However, the capacity to utilize citrulline in these pigs at birth is high and thus citrulline supplementation in neonatal, including premature, pigs is a viable option to increase arginine availability.

Technical Abstract: Developmental changes in the renal expression and activity of argininosuccinate synthase (ASS1) and lyase (ASL), enzymes that utilize citrulline for the production of arginine, have been reported. Thus the ability of neonates, and especially premature ones, to produce arginine may be compromised. To determine the utilization of citrulline in vivo, we measured renal expression of ASS1 and ASL and conducted citrulline compartmental and non-compartmental kinetics using [15N] citrulline in pigs of five different ages (from 10 d preterm to 5 weeks of age). The tracer was given in substrate amounts to also test the ability of neonatal pigs to utilize exogenous citrulline. Preterm and term pigs at birth had lower ASS1 and ASL expression than older animals, which was reflected in the longer half-life of citrulline in the neonatal groups. The production and utilization of citrulline by 1 week old pigs was greater than in pigs of other ages, including 5 week old animals. Plasma citrulline concentration was not able to capture these differences in citrulline production and utilization. In conclusion, the developmental changes in renal ASS1 and ASL gene expression are reflected in the ability of the pigs to utilize citrulline. However, it seems that there is an excess capacity to utilize citrulline at all ages, including during prematurity, since the bolus dose of tracer did not result in an increase in endogenous citrulline. Our results support the idea that citrulline supplementation in neonatal, including premature, pigs is a viable option to increase arginine availability.