Normal growth depends upon rapid rates of protein accretion in premature and normal neonates. Increases in protein synthesis and/or reductions in proteolysis are necessary for effective protein accretion; clinically it continues to be difficult to achieve adequate protein accretion in extremely premature newborns. Recent data has demonstrated that intravenous nutrition is least effective in reducing whole body proteolysis in the most immature infants. The reasons for this apparent resistance to suppressing proteolysis in extremely premature neonates remains unclear, and to what extent altering nutrient delivery can more effectively support protein anabolism in this population in uncertain. The present application will test the overall hypothesis that the most immature neonates are the most sensitive to incomplete amino acid availability. Specifically, more complete intravenous amino acid solutions are necessary to improve whole body protein anabolism, and an enteral amino acid supply is required to support effective splanchnic protein anabolism. To evaluate this overall hypothesis, the following specific aims will be pursued in extremely premature, premature and term newborns: 1) To assess how altering amino acid composition during intravenous nutrition affects whole body proteolysis, protein synthesis and amino acid balance. Leucine and phenylalanine kinetics will be determined during the sequential addition of the conditional essential amino acids tyrosine and cysteine to a parenteral nutrition mixture. 2) To measure the splanchnic uptake of essential amino acids in response to graded enteral protein intakes. Whole body and dietary leucine and phenylalanine kinetics will be assessed using intravenous and enteral tracers. 3) To evaluate the effect of combined parenteral enteral nutrition on the splanchnic uptake of essential amino acids and whole body proteolysis and protein synthesis. Whole body and dietary leucine and phenylalanine kinetics will be measured during parenteral and combined parenteral and enteral nutrition. 4) To determine how the route of nutrient delivery effects the synthesis of a hepatically derived protein. The fractional synthetic rate of the albumin will be measured during enteral and parenteral nutrient intake. Performing these studies will better define the nutritional regulation of protein metabolism in premature and term newborns as well as providing scientific rationale for designing improved feeding regiments for this population.
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