DIETARY METHIONINE UPTAKE BY SPLANCHNIC REGION

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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. The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism and selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. During critical illness the splanchnic area is profoundly affected, and may influence amino acid metabolism. There are limited data on inter-organ amino acid exchange and the role of splanchnic uptake and catabolism of amino acids in critically ill patients. To determine parenteral and enteral amino acid requirements, it is necessary to determine the extent of the first pass disappearance of amino acids in the splanchnic region. We plan to study a group of healthy adolescents who will serve as controls for our critically ill adolescent group. HYPOTHESIS Sulfur amino acid splanchnic uptake in healthy adolescents has not been determined and needs to be define. Hence enteral requirement of sulfur amino acids in sick children need to be defined. SPECIFIC AIMS The first objective of this protocol is to conduct studies of methionine and cysteine splanchnic uptake in healthy children adolescents. The studies in healthy children will serve as controls for our critically ill population. We are requesting GCRC support to conduct our studies in the healthy children. We aim to conduct primed, constant simultaneous intravenous and enteral infusions of L-[1-13C] and L[2H2 ]methionine in a first set of studies and of L-[1-13C] and L[2H2 ] cysteine in a second set of studies in healthy children and to use these data to estimate the contribution of splanchnic sequestration to methionine and cysteine requirements. Primary Endpoint: The fraction of methionine or cysteine tracer that disappears in a first-pass through the splanchnic area BACKGROUND AND SIGNIFICANCE This protocol is a continuation of our studies on sulfur amino acid metabolism in sick children. We have already conducted studies of methionine splanchnic uptake in critically ill infants, children and adolescents (Please see preliminary data). The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism. The splanchnic area selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. Intestinal amino acid metabolism plays an important role in modulating the entry of absorbed dietary amino acids into the portal circulation. Thus, the pattern of amino acids in the diet differs markedly from that in portal venous blood and does not reflect their availability to extraintestinal tissues. This concept has important implications for protein and amino acid nutrition. The extensive catabolism of dietary essential amino acids in the first pass by the small intestine, a large organ in the body, results in decreased nutritional efficiency. Thus, intestinal amino acid metabolism will influence the utilization efficiency of dietary amino acids and therefore their requirements. Furthermore, it is not known how inter-organ amino acid exchange and splanchnic uptake are affected under pathologic conditions, and how these processes influence amino acid requirements under conditions of disease. There are data on the splanchnic uptake of leucine, arginine, glutamine and methionine in healthy subjects. In the pediatric population there are two studies on leucine splanchnic uptake, in a population of patients with cystic fibrosis and in the newborn period. These studies yield leucine splanchnic uptake values of 24% and 30% respectively. There are no data on methionine and cysteine splanchnic uptake in healthy or sick children. Therefore, the first objective of this proposal is to determine the rates of splanchnic uptake of methionine and cysteine in sick children.