Mechanisms of Dipeptide Uptake by Rat Small Intestine in Vitro

Abstract

1. The uptake of l-methionine and glycine as free amino acids, and from their dipeptides by everted rings of rat small intestine in vitro has been investigated. The concentrations used covered a wide range, including values likely to be near those found in the lumen of the intestine. 2. Though no intact peptides were found in the mucosal cells, evidence was obtained which showed that hydrolysis of the peptides was cellular at all concentrations. Total hydrolysis of peptides by the intestine was very great in relation to amino acid uptake over very short incubation times, suggesting that much hydrolysis took place superficially. 3. Except at the lowest concentrations, the rates of uptake of amino acids from the peptides were more rapid than from the equivalent amino acid mixtures. Competition for uptake between glycine and methionine was avoided when they were presented in the form of l-methionylglycine. 4. Anoxia inhibited uptake of methionine from free l-methionine and from l-methionyl-l-methionine. It also inhibited hydrolysis of l-methionyl-l-methionine by intact intestine, but not by intestinal homogenates, suggesting that peptide uptake may be energy-dependent. The l-amino acid oxidase of snake venom, which destroys l-methionine but has no effect on glycine or on the peptides studied, inhibited methionine uptake from peptides when present at high concentrations, suggesting that a major site of hydrolysis is enzyme-accessible. 5. It is suggested that there may be two modes of uptake of amino acids from oligopeptides: (1) surface hydrolysis by mechanisms closely linked to the amino acid entry mechanisms, and (2) peptide entry into the mucosal cells by a special mechanism, followed by intracellular hydrolysis.

Amino Acid Transport Pathways in the Small Intestine of the Neonatal Rat

“…Proline and glycine probably have affinities for both neutral amino acid transport pathways [22]. Table IV shows the intracellular accumulation of Cycloleucine (14) 2.28 ± 0.13 a-Aminoisobutyric acid (15) 0.30 ± 0.03 0-Alanine (11) 0.23 ± 0.04 T-Aminobutyric acid (8) 0.15 ± 0.02 1 Except for the substitution of the indicated 0, 7, and nonmetabolized amino acids, the methods used in obtaining and expressing the results are the same as for Table I. some amino acids utilizing the imino acid-glycine pathway. Although their accumulations were appreciably lower than those of the neutral amino acids shown in Table I, accumulations o£ the amino acids that used both neutral amino acid pathways (i.e., glycine and proline) were significantly greater (P < 0.001) than the very slow accumulations of the amino acids that used only the imino acid-glycine pathway (i.e., betaine and sar cosine).…”

“…Recent studies have indicated that the intestinal absorption of amino acids from dipeptides occurs more rapidly than from the free amino acid [11,19] and is apparently mediated by an independent transport system [8,33]. Since low molecular weight peptides account for most of the nitrogenous material in the intestinal lumen during digestion of a protein meal [7,21], this transport system may represent a potentially important pathway for mediating amino acid absorption from dietary protein.…”

Effects of Pro-Arg, a Novel Dipeptide Derived from Protamine Hydrolysate on H2O2-Induced Oxidative Stress in Human Diploid Fibroblasts

“…Previously reported indicated dipeptides can enter cells both in vitro and in vivo. 41,42) Therefore, this dipeptide, Pro-Arg, may enter the cultured cells. However, whether it can enter cells fully or partially needs further investigation.…”

The Responses of Rat Intestinal Brush Border and Cytosol Peptide Hydrolase Activities to Variation in Dietary Protein Content DIETARY REGULATION OF INTESTINAL PEPTIDE HYDROLASES

“…Evidence from in vitro (26) and in vivo (27) studies has been interpreted as suggesting two modes of peptide transport, (a) surface hydrolysis by mechanisms closely linked to the amino acid entry mechanisms, and (b) peptide entry into mucosal cells by a special mechanism, followed by intracellular hydrolysis. It was of interest, therefore, to determine whether or not the activities of intestinal peptide hydrolases are regulated by dietary protein in a manner analagous to the regulation of intestinal disaccharidases by dietary carbohydrate.…”