PEPTIDE ASSIMILATION IN MALNUTRITION AND MALABSORPTION

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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.