Previous studies have shown that dipeptides, when introduced into the lumen of human intestine are taken up intact by a peptide transport system, and are partly hydrolyzed to amino acids by brush-border membrane enzymes. The positioning of glycine in the N-terminal position appears to increase the opportunity for intact transport of dipeptides at the expense of reducing brush-border membrane hydrolysis. In a preliminary study, we have compared absorption rates of amino acids from a mixture of dipeptides and a corresponding amino acid mixture. The dipeptide mixture consisted of a series of dipeptides all having glycine in the N-terminal position and either an essential or non-essential amino acid in the C-terminal position. These results have shown: a) the rates of amino acid absorption are considerably greater from the dipeptide than amino acid mixtures, and b) the competition for absorption is minimized or abolished when amino acids are presented in dipeptide rather than in free form. We believe these findings may have useful clinical application in the practice of enteral nutrition, which currently utilizes either amino acid mixtures or protein hydrolysates as the source of nitrogen. We believe a dipeptide mixture may be superior to either free amino acids or protein hydrolysates. To investigate our hypothesis, we have proposed a series of experiments to determine the efficacy of absorption from the dipeptide mixture in the conditions which usually may require enteral nutrition therapy, such as short bowel syndrome, intestinal disease, pancreatic insufficiency, and malnutrition. In view of the fact that very little information is available on the kinetics of peptide absorption or hydrolysis in conditions of malnutrition and intestinal disease in man, we have designed a series of experiments to investigate this problem. Finally, a series of experiments is designed to investigate parameters of nutrition and metabolism and parameters of intestinal morphology, composition, metabolism, and function when a dipeptide mixture replaces an amino acid mixture as the source of nitrogen for enteral nutrition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK015861-12
Application #
3225481
Study Section
(GCN)
Project Start
1978-06-15
Project End
1986-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
12
Fiscal Year
1986
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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