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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK015861-14
Application #
3225482
Study Section
Nutrition Study Section (NTN)
Project Start
1978-06-15
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
14
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Adibi, S A; Schenker, S; Morse, E (1996) Mechanism of clearance and transfer of dipeptides by perfused human placenta. Am J Physiol 271:E535-40
Daniel, H; Adibi, S A (1994) Functional separation of dipeptide transport and hydrolysis in kidney brush border membrane vesicles. FASEB J 8:753-9
Adibi, S A; Lochs, H; Abumrad, N N et al. (1993) Removal of glycylglutamine from plasma by individual tissues: mechanism and impact on amino acid fluxes in postabsorption and starvation. J Nutr 123:325-31
Daniel, H; Adibi, S A (1993) Transport of beta-lactam antibiotics in kidney brush border membrane. Determinants of their affinity for the oligopeptide/H+ symporter. J Clin Invest 92:2215-23
Vazquez, J A; Raghunath, M; Adibi, S A (1992) Uptake and hydrolysis of glycylglutamine at the blood-brain barrier. Metabolism 41:121-4
Daniel, H; Morse, E L; Adibi, S A (1992) Determinants of substrate affinity for the oligopeptide/H+ symporter in the renal brush border membrane. J Biol Chem 267:9565-73
Minami, H; Daniel, H; Morse, E L et al. (1992) Oligopeptides: mechanism of renal clearance depends on molecular structure. Am J Physiol 263:F109-15
Minami, H; Morse, E L; Adibi, S A (1992) Characteristics and mechanism of glutamine-dipeptide absorption in human intestine. Gastroenterology 103:3-11
Lochs, H; Hubl, W; Gasic, S et al. (1992) Glycylglutamine: metabolism and effects on organ balances of amino acids in postabsorptive and starved subjects. Am J Physiol 262:E155-60
Daniel, H; Morse, E L; Adibi, S A (1991) The high and low affinity transport systems for dipeptides in kidney brush border membrane respond differently to alterations in pH gradient and membrane potential. J Biol Chem 266:19917-24

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