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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Unknown (R22)
Project #
5R22DK015856-17
Application #
3566273
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1983-09-01
Project End
1992-03-31
Budget Start
1990-07-01
Budget End
1991-03-31
Support Year
17
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Tharakan, John F; Yu, Yong M; Zurakowski, David et al. (2008) Adaptation to a long term (4 weeks) arginine- and precursor (glutamate, proline and aspartate)-free diet. Clin Nutr 27:513-22
Louis, Magali; Poortmans, Jacques R; Francaux, Marc et al. (2003) Creatine supplementation has no effect on human muscle protein turnover at rest in the postabsorptive or fed states. Am J Physiol Endocrinol Metab 284:E764-70
Chen, Chung-Lin; Fei, Zhewei; Carter, Edward A et al. (2003) Metabolic fate of extrahepatic arginine in liver after burn injury. Metabolism 52:1232-9
Argaman, Zvi; Young, Vernon R; Noviski, Natan et al. (2003) Arginine and nitric oxide metabolism in critically ill septic pediatric patients. Crit Care Med 31:591-7
Rand, William M; Pellett, Peter L; Young, Vernon R (2003) Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr 77:109-27
Yu, Yong-Ming; Ryan, Colleen M; Fei, Zhe-Wei et al. (2002) Plasma L-5-oxoproline kinetics and whole blood glutathione synthesis rates in severely burned adult humans. Am J Physiol Endocrinol Metab 282:E247-58
Young, V R; Ajami, A M (2001) Metabolism 2000: the emperor needs new clothes. Proc Nutr Soc 60:27-44
Lyons, J; Rauh-Pfeiffer, A; Ming-Yu, Y et al. (2001) Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. Crit Care Med 29:870-7
Yu, Y M; Ryan, C M; Castillo, L et al. (2001) Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal. Am J Physiol Endocrinol Metab 280:E509-17
Forslund, A H; Hambraeus, L; van Beurden, H et al. (2000) Inverse relationship between protein intake and plasma free amino acids in healthy men at physical exercise. Am J Physiol Endocrinol Metab 278:E857-67

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