This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Threonine, a non-transaminating essential amino acid, is involved in a number of metabolic processes such as protein synthesis; signal transduction cascades, collagen synthesis and glycine biosynthesis. The catabolism of threonine is complex involving enzymes in the cytoplasmic and in the mitochondrial compartment. Threonine is predominantly metabolized by the splanchnic tissues (liver and gut). Published studies in human adults and in animals suggest developmental differences in threonine catabolism. Studies have also shown that the plasma level of threonine is higher in premature infants receiving parenteral or enteral nutrition. Our data show that premature infants receiving parenteral nutrition have a two-fold increase in the plasma concentration of threonine and higher plasma levels of glycine compared to term infants. It is hypothesized that higher plasma levels of threonine in premature infants are a consequence of higher rate of protein turnover, an enzymatic immaturity of threonine catabolizing enzymes and a lower rate of threonine oxidation. Intravenous administration of exogenous amino acids (parenteral nutrition) bypasses the first pass metabolism of threonine and will lead to a further increase in the plasma level of threonine. Although threonine does not contribute to the synthesis of glycine in newborn infants; a higher level of threonine in premature infants will interfere with metabolism of glycine resulting in higher plasma levels of glycine. In the proposed study, premature infants less than 32 weeks gestation and less than/or equal to 1500 grams birth weight will be recruited. Infants will be studied while they are acutely ill and while growing and receiving full enteral nutrition. Premature infants will be randomized to receive either intravenous glucose solution or total parenteral nutrition containing 3g/kg/d of protein (providing 44 millimol/kg/h of threonine) within 72 hours after birth. Using stable isotopic tracers, the effect of total parenteral nutrition on threonine kinetics, rate of oxidation of threonine, contribution of threonine to glycine, impact of plasma threonine levels on the conversion of glycine to serine and relationship of threonine kinetics to whole body protein turnover and protein oxidation will be examined. In a separate group of growing premature infants, the effect of enteral nutrition (containing 60 millimol/kg/h of threonine) on the above parameters will be examined.
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