This is a continuation grant application to explore quantitative aspects of the metabolism of specific, conditionally indispensable or dispensable amino acids in the intact, healthy human adult. Earlier nitrogen balance studies demonstrated the nutritional indispensability of nine amino acids, with the other common amino acids of tissue proteins classified as being dispensable. The classification is no longer satisfactory as nutrition and metabolic knowledge has advanced. It is hypothesized that the cellular availability of the nutritionally dispensable amino acids for meeting physiologic needs is determined by the nitrogen and amino acid composition of the diet and in turn affected by the dynamic status of tissue and organ protein turnover. Unique stable isotope tracer approaches will be exploited to quantify in vivo aspects of some of these amino acids under well-defined nutritional conditions. Specifically we will (a) establish stable isotope tracer models for investigating quantitative aspects of the metabolism of specific dispensable, or conditionally indispensable, amino acids- these are (i) the proline, arginine and ornithine """"""""triad"""""""" (11) tyrosine and (iii) cystine; (b) explore the consequences of alterations in the dietary intake of total nitrogen and/or specific amino acids on the metabolism of the foregoing amino acids, using the improved stable isotope probes and approaches for this purpose: (c) explore the kinetics of the interrelationships between selected indispensable amino acids (leucine and threonine) and the dietary supply of dispensable amino acids. The proposed studies will identify in vivo physiological mechanisms responsible for changes in the metabolism of specific dispensable amino acids. The longer-term objective of this research is to achieve a more complete understanding about the in vivo regulation and integration of """"""""dispensable amino acids. The longer- term objective of this research is to achieve a more complete understanding about the in vivo regulation and integration of """"""""dispensable' amino acid metabolism and the quantitative contribution made to the nitrogen economy of the intact human host. From this understanding it will be possible to improve upon diagnostic tools taken to assess protein and amino acid nutritional status, on the one hand, and the nutritional requirements, on the other, of the human subject under differing patho-physiological conditions.
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