MECHANISMS OF NEONATAL PROTEIN ACCRETION

Project: Research project

Description

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.
StatusFinished
Effective start/end date5/1/9212/31/07

Funding

  • National Institutes of Health: $170,255.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $324,536.00
  • National Institutes of Health: $324,536.00
  • National Institutes of Health
  • National Institutes of Health: $316,910.00
  • National Institutes of Health: $331,025.00
  • National Institutes of Health: $216,434.00
  • National Institutes of Health: $307,719.00
  • National Institutes of Health
  • National Institutes of Health: $220,823.00
  • National Institutes of Health
  • National Institutes of Health

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Extremely Low Birth Weight Infant
Proteins
Energy Metabolism
neonates
proteolysis
protein synthesis
protein metabolism
Proteolysis
Growth
parenteral feeding
essential amino acids
phenylalanine
leucine
amino acids
enteral feeding
Pregnancy
Leucine
kinetics
proteins
Calorimetry

ASJC

  • Medicine(all)