Amino acids suppress proteolysis independent of insulin throughout the neonatal period.

To determine how increased amino acid availability alters rates of whole body proteolysis and the irreversible catabolism of the essential amino acids leucine and phenylalanine throughout the neonatal period, leucine and phenylalanine kinetics were measured under basal conditions and in response to intravenous amino acids in two separate groups of healthy, full-term newborns (at 3 days and 3 wk of age). The endogenous rates of appearance of leucine and phenylalanine (reflecting proteolysis) were suppressed equally in both groups and in a dose-dependent fashion (by approximately 10% with 1.2 g x kg(-1) x day(-1) and by approximately 20% with 2.4 g x kg(-1) x day(-1)) in response to intravenous amino acid delivery. Insulin concentrations remained unchanged from basal values during amino acid administration. The irreversible catabolism of leucine and phenylalanine increased in a stepwise fashion in response to intravenous amino acids; again, no differences were observed between the two groups. This study clearly demonstrates that the capacity to acutely increase rates of leucine oxidation and phenylalanine hydroxylation is fully present early in the neonatal period in normal newborns. Furthermore, these data suggest that amino acid availability is a primary regulator of proteolysis in normal newborns throughout the neonatal period.

Acute changes in leucine and phenylalanine kinetics produced by parenteral nutrition in premature infants.

To determine the effect of parenteral nutrition on the balance and catabolism of leucine (by oxidation) and phenylalanine (by hydroxylation) and to assess any acute changes in proteolysis and/or protein synthesis, leucine and phenylalanine kinetics were measured by stable isotope tracer infusions in nine 32-wk gestation premature infants under both basal conditions and in response to an i.v. infusion of glucose, lipid, and amino acids. Leucine and phenylalanine balance both changed from negative to positive during parenteral nutrition. However, leucine and phenylalanine catabolism were differently affected by parenteral nutrition; the rate of leucine oxidation increased 2-fold, whereas the rate of phenylalanine hydroxylation was unchanged from basal values. Phenylalanine utilization for protein synthesis and leucine utilization for protein synthesis (based on both plasma leucine and alpha-ketoisocaproic acid enrichments) increased significantly during parenteral nutrition. The endogenous rates of release of leucine (based on plasma leucine enrichment) and phenylalanine (both reflecting proteolysis) were significantly reduced during parenteral nutrition. The endogenous rate of release of leucine (based on alpha-ketoisocaproic acid enrichment) was slightly but not significantly lower during parenteral nutrition. The substantial increase in leucine oxidation without changes in phenylalanine hydroxylation suggests a possible limitation in the phenylalanine/tyrosine supply during parenteral nutrition. In addition, these results suggest that premature infants respond to parenteral nutrition with acute increases in whole body protein synthesis as well as a probable reduction in proteolysis.

Proteolysis and phenylalanine hydroxylation in response to parenteral nutrition in extremely premature and normal newborns.

To determine to what extent intravenous nutrition can reduce proteolysis in very immature and normal newborns, and to assess the capacity of preterm and normal newborns to convert phenylalanine to tyrosine, phenylalanine and leucine kinetics were measured under basal conditions and during parenteral nutrition in clinically stable, extremely premature (approximately 26 wk of gestation) infants and in normal term newborns. In response to parenteral nutrition, there was significantly less suppression (P < 0.001) of endogenous leucine and phenylalanine rate of appearance in extremely premature infants compared with term infants. Phenylalanine utilization for protein synthesis during parenteral nutrition increased significantly (P < 0.01) and by the same magnitude (approximately 15%) in both extremely premature and term infants. Phenylalanine was converted to tyrosine at substantial rates in both extremely premature and term infants; however, this conversion rate was significantly higher (P < 0.05) in extremely premature infants during both the basal and parenteral nutrition periods. These data provide clear evidence that there is no immaturity in the phenylalanine hydroxylation pathway. Furthermore, although parenteral nutrition appears to produce similar increases in protein synthesis in extremely premature and term infants, proteolysis is suppressed much less in extremely premature newborns. The factors responsible for this apparent resistance to suppression of proteolysis in the very immature newborn remain to be elucidated.