Dynamics of human whole body amino acid metabolism: use of stable isotope probes and relevance to nutritional requirements.

Introduction An improved definition of the requirements for nitrogen and indispensable amino acids in human protein nutrition depends upon a better understanding of the mechanisms responsible for, and nature of, the integration of protein and amino acid metabolism at the whole body level. Although the molecular and cellular events concerned with gene expression (e.g. 1, 2), the formation of tissue and organ proteins (3, 4) and their subsequent breakdown (5, 6) have been outlined, to some extent in great detail, in recent years, the relationships between these molecular, subcellular and organ-specific processes and the maintenance of nutritional status of the intact host remain to be vigorously explored. It is crucial that these relationships be defined if knowledge of protein and amino acid nutrition is to extend much beyond a stage that might be characterized, at present, as being rather empirical and, at times, almost naive. For this reason our research during the past few years has attempted to develop a more complete picture of the organization of whole body protein and amino acid metabolism and how it is affected by various nutritional and non-nutritional factors (e.g. 7-11). In this invited paper, some recent work that we have undertaken at MIT, also in collaboration with others, will be reviewed in order to explore, in greater depth, the physiology of body protein and amino acid metabolism in adult human subjects. Our purpose has been to try to determine how the nitrogen economy of the host is maintained under differing nutritional and physiological conditions. At the outset, it should be mentioned that although our work has been stimulated by many investigators a few of them deserve particular recognition; the pioneering work of Waterlow and his colleagues, conducted initially in Jamaica and