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Citrulline and de novo arginine synthesis in perinatal and young pigs
Arginine is a conditional essential amino acid that becomes essential when its demand (e.g., growth, disease) exceeds its production. The endogenous synthesis of arginine is a multiorgan process where citrulline synthesized by the gut is utilized by two renal enzymes (arginine succinate lyase and synthase, ASS and ASL) to produce arginine. Because ASS and ASL are present in the gut of neonatal pigs, it is believed that the intestinal-renal axis for arginine synthesis is not functional in the newborn. However, this is not consistent with the high plasma citrulline concentrations seen in perinatal pigs.
To address this apparent paradox we measured citrulline production and concentrations in premature (P-10; 10d preterm and 1.0±0.1 kg BW), neonatal (P8; 8d and 2.5±0.2 kg BW) and young pigs (P30; 30d and 7.5±0.3 kg BW). We also utilized stable isotopes to study the interorgan production of citrulline and arginine in neonatal and young pigs.
Premature pigs (P-10) have a reduced (P < 0.001) ability to produce citrulline (23±2 µmol•kg-1•h-1) when compared with older animals (74±4 and 41±3 µmol•kg-1•h-1, P8 and P30). Plasma citrulline concentrations, however, were not different (P = 0.31; 171, 190 and 145 µmol/L, P-10, P8 and P30 respectively). A substantial dilution of the citrulline tracer in the portal circulation of P8 and P30 pigs indicated enteral citrulline production. Likewise, the appearance of labeled arginine in the renal vein demonstrated citrulline utilization for arginine synthesis by both age groups. Based on the labeling pattern of the arginine released by the PDV we were unable to detect any arginine synthesis by the gut; the arginine released by the PDV was likely to originate from protein breakdown since the essential amino acid phenylalanine was also released. The quantitation of organ fluxes indicated a production of 22±7 and 21±7 µmol of citrulline/L blood flow by the PDV (P8 and P30) and a renal conversion into arginine of 19±7 and 16±5 µmol/L blood flow. This demonstrates that the intestinal-renal axis for arginine synthesis is present in the neonatal pig. Although ASS and ASL were present in the small intestine of P8 pigs, they were localized in the tip of the villus whereas the enzymes responsible for the synthesis of citrulline were present in the base and crypt. The lack of co-localization of these enzymes prevents the gut from synthesizing arginine and explains the high levels of circulating citrulline observed in perinatal pigs.
Keywords: arginine, citrulline, neonate, pig, tracer