Our overall objective is to gain insight into the mechanism 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. In the present proposal we will test the following hypotheses: 1) The mechanism of protein accretion in response to feeding is influenced by the basal rates of protein synthesis and proteolysis. Infants with high basal rates of protein synthesis and proteolysis will respond to nutrient intake by reducing proteolysis; infants with lower rates of breakdown and synthesis during fasting will respond by increasing synthesis. Because protein turnover decreases with advancing age, we propose that premature newborns will accrete protein primarily by reductions in proteolysis, and older infants by increased protein synthesis. We hypothesize that the switch point is term gestation. 2) Amino acids, rather than nonprotein substrate, are the major effectors of changes in protein synthesis or proteolysis. While provision of nonprotein substrate may have some effect on protein metabolism (especially at high basal proteolysis rates), we postulate that provision of amino acids will have a far greater effect on reducing proteolysis and/or stimulating protein synthesis.
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