Protein is accreted at high rates in early postnatal life; failure to achieve normal protein retention 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. Protein synthesis and breakdown rates are both elevated in immature individuals; this high rate of protein turnover appears to be required for the tissue remodeling and rapid growth. Ultimately, it is the balance between protein synthesis and proteolysis which determines whether protein accretion (and growth) will be achieved. During postnatal life this balance continuously shifts in response to intermittent nutrient intake; rates of protein synthesis and proteolysis must therefore change in response to nutrient availability. 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 suppress 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. 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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