Following absorption from the gastrointestinal (GI) tract and transport in the protal circulation, nutrients are firs influenced by metabolic processes in the liver and GI tract. Depending upon the rate and extent of these processes, a certain fraction of the enterally administered nutrient may be taken up and utilized exclusively in these organs. This is referred to as first-pass metabolism (FP). In addition to metabolic processes in the splanchnic bed, FP may be influenced by the rate of intermixing of the systemic and portal compartments. As a result of FP metabolism, enteral feeding and intravenous nutrition administration may lead to different metabolic consequences in visceral and peripheral tissues. Recent evidence indicates that FP metabolism of exogenous leucine increases during feeding. We postulate that this represents a higher availability of leucine during enteral feeding in comparison to parenteral feeding. The proposed work will focus on this phenomenon, emphasizing varying levels of dietary leucine intake. A rat model, employing multiple 13-C and 14-C tracer infusions, will be used for quantification of total FP as well as FP oxidation and transamination into alpha-ketoisocaproate (KIC). The selective utilization of enteral leucine in gastrointestinal and liver protein synthesis will also be measured at different levels of intake. The relationship between labelled CO2 appearance in expired breath in comparison to plasma leucine and KIC enrichment, following simultaneous tracer infusions into the system circulation, the GI tract, and the portal circulation will be studied. These studies will be extended into a burned rat model for evaluation of FP leucine metabolism under hypermetabolic conditions. Measurement of blood flow rates will allow calculation of distribution of systemic leucine to tissues. Simultaneously, protein synthesis and degradation rates, as well as the rate of distribution of enterally administered leucine tracer will be measured. By correlating FP leucine metabolism and availability of exogenous leucine (both enteral and parenteral), with splanchnic protein synthesis and breakdown, we will test the hypothesis that the route of nutritional administration affects nutrient requirements under the increased demands of stress.
