METABOLISM AND CLINICAL APPLICATION OF OLIGOPEPTIDES

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For over two decades we have been investigation various questions concerned with assimilation of oligopeptides. These investigations have included transport and hydrolysis of dipeptides and metabolism of their amino acid residues. Although our research has produced considerable amounts of new information on metabolism of oligopeptides, particularly dipeptides, there are still many questions that remain unanswered. The aim of this grant application is to provide answers to some of these questions by completing seven research projects. In the first project we will investigate the digestive and absorptive function of the intestinal mucosal membrane and protein metabolism when dipeptides are the sole source of dietary nitrogen in man. In the second project we will investigate the importance of peptide entry into portal circulation after a protein meal or during enteral nutrition with dipeptides in dogs. In the third project we will investigate the influence of molecular structure on assimilation of dipeptides by isolated liver, muscle, kidney, brain, and red cells in rats. In the fourth project we will investigate metabolism of the alpha-aminonitrogen and the carbon skeleton of dipeptides during continuous IV dipeptide infusion in rats. In the fifth project we will investigate the effects of dietary and hormonal alterations on metabolism of dipeptides by liver, muscle and kidney in rats. In the sixth project we will investigate whether restoration of body protein of patients by parenteral nutrition in enhanced by provision of tyrosine, glutamine, and cysteine as glycyl- dipeptides. Due to problems either in solubility or stability, parenteral amino acid solutions lack these amino acids. In the seventh project we will investigate whether peptide assimilation by liver, muscle, kidney and gut in vivo in dogs would differ if the size of peptide were increased from 2 to 3 residues (tripeptides). The basis for the above studies has been detailed in the grant application. A wide range of techniques, validated either by us or by other investigators, are proposed for investigation of each project. We believe that completion of the above projects will sufficiently advance the field of peptide metabolism to a stage which will allow a wide clinical application of peptides to the practice of enteral and parenteral nutrition. The importance of enteral and parenteral nutrition is underscored by the fact that patients who are unable to maintain their nutrition no longer need to suffer the serious consequences of malnutrition.