The long-term goal of this PSA proposal is to develop fundamental basic science and clinical research skills which will enable the applicant to develop an independent research career in the areas of nutritional metabolism, indirect calorimetry and, tracer methodology. Phase 1 focuses on developing the background, technical skills and instrumentation in several distinct fields to successfully perform the clinical studies in Phase 2. Phase 1 will establish basic science laboratory skills in cell culture and amino acid metabolism using tracer techniques and enzyme determinations. Specifically, the precursors and enzyme activities of fetal hepatic serine biosynthesis through the glycolytic pathways in normal and growth retarded fetuses will be identified. Didactic training will focus on nutrition, statistics and the theoretical and technical aspects of mass spectrometry. In addition, laboratory validation of indirect calorimetry under conditions of supplemental oxygen and mechanical ventilation will be performed. Phase 2 will focus on nutritional studies in neonates weighing less than 1000 g, extremely-low- birthweight (ELBW) infants. The optimal strategy for supplying nutrition to these infants is poorly defined because of limited information on their substrate metabolism. In the recently published NICHD Executive Summary of its proposed five-year nutrition research plan, there is a recognition of suboptimal nutrition in the ELBW infant, and of the need for further investigation in this area, particularly in the first days of life. We propose to study protein kinetics and the effects of the quality of the infused energy on protein metabolism in the ELBW infant in the first 48 hours of life using stable isotope methodology combined with indirect calorimetry. In longitudinal studies, we will assess changes in protein metabolism in ELBW infants in the first 2 weeks of life. These studies are designed to extend the ability to study metabolism in ELBW infants, and to provide information on substrate kinetics that will be critical to developing rational nutritional strategies for the ELBW infant.
