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. This portocol is a continuation of our studies on sulfur amino acid metabolism in critically ill septic children. The immediate objectives of this project are to better define sulfur amino acid requirements in the healthy and in the critically ill septic pediatric population from newborn to adolescent. This is an ambitious goal that can only be approached with one project at a time. In this proposal we are focused exclusively in the healthy and critically ill adolescent population. Amino acid requirements in healthy children are based on extremely limited data. The amino acid requirements for critically ill children in therms of nutritional and functional balance are not known. Methionine, an indispensable sulfur amino acid serves for protein synthesis in addition to DNA methylation and biosynthesis of important compounds such as creatine, choline, etc. However, an excessive methionine administration may contribute to endothelial dysfunction of critical illness through an excessive production of homocysteine. In the present studies we propose to define nutritional requirements of methionine and to begin to explore functional requirements in 196 critically ill septic adolescents and 196 healthy adolescents over a period of 5 years. We propose to modify the """"""""gold"""""""" standard techniqure of amino acid requirement determination, the 24h-indicator amino acid oxidation and balance technique, to make it applicable to both, the healthy and critically ill populations. We plan also to correlate methionine intake with severity of disease, markers of endothelial dysfunction and rates of DNA methylation in peripheral lymphocytes. Our long-term aim is to eventually determine the amino acid requirements that will maintain nutritional balance and function in the pediatric population from newborn to adolescents, to improve outcome in the sick population and to establish sound nutritional standards based on quantitative, reliable data in the healthy pediatric population.
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