Protein is accreted at high rates in early postnatal life; failure to achieve normal protein accretion results in abnormal growth, which is accompanied by significant morbidity and mortality. Although studies assessing the rate of protein gain have been prevalent, the physiologic processes underlying normal protein accretion have not been well elucidated. Our overall objective is to gain insight into the mechanisms of protein accretion in early postnatal life: specifically, to assess how nutrient intake may increase protein synthesis and/or restrain proteolysis, and to examine how these processes may be affected by the stage of development. Preliminary data from our laboratory suggest that the modulating effect of nutrient intake on protein kinetics in the immature infant is dependent upon the underlying rates of protein breakdown and synthesis. Infants with the highest rates of protein breakdown may reduce proteolysis to effect net retention of protein, whereas infants with lower basal rates of proteolysis may respond to nutrient intake with increased protein synthesis to ensure nitrogen accretion. In the present proposal we will test two hypotheses: 1) The mechanism of protein accretion in response to feeding is influenced by the basal rates of protein synthesis and proteolysis. 2) Amino acids, rather than nonprotein substrate, are the major effectors of changes in protein synthesis or proteolysis. To test these hypotheses, leucine and phenylalanine kinetics (as a model to reflect protein synthesis and proteolysis) will be determined with steady state tracer infusions of 1-13C leucine and d5 phenylalanine combined with respiratory calorimetry in selected populations of infants.
Three specific aims will be pursued: 1) To determine how intermittent nutrient intake acutely alters basal rates of protein synthesis and proteolysis at advancing developmental stages. 2) To evaluate the separate effects of nonprotein substrate and amino acids on protein kinetics. 3) To assess the interactive effects of nonprotein substrate and amino acids on protein kinetics. The information gained by performing these studies will result in valuable insight into the physiology of protein accumulation, and thus the growth process. Ultimately, this knowledge may provide a basis for improved nutritional management of sick and premature newborns.
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