No 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.

I . The absorption rates of L-methionine and L-methionyl-L-methionine (dimethionine) from the upper jejunum and lower ileum of the rat were studied in vivo after different dietary treatments. Rates were expressed per unit gut length and per unit gut weight; the former was considered to be the more satisfactory under the different dietary conditions.2. The dietary treatments were either short-term (10 d) or long-term (40-84 d).3. The rate of absorption of methionine increased in the jejunum after a restricted dietary intake, a high-protein diet or a high-methionhe diet, but decreased after long-term protein deprivation. Short-term dietary restriction had a similar effect on methionine absorption in jejunum and ileum, though less pronounced in the latter. The rate of absorption of dimethionine was less influenced by dietary changes than that of methionine. 4.Under all conditions studied, the absorption rate of methionine was greater when presented as the dipeptide than when presented as the equivalent amount of free amino acid. This confirms that dimethionine is taken up intact from the intestinal lumen, and it seems likely that there are different mechanisms of mucosal uptake for methionine and its dipcptide.Preliminary investigations of absorption rates of methionine and the dipeptide L-methionyl-L-methionine (dimethionine) after a short period of reduced dietary intake (a dietary condition referred to as 'semistarvation' by Crampton, showed that reduced food intake increased the absorption of both amino acid and peptide, but that the effect on absorption of the peptide was less marked. This suggested that the mechanisms of intestinal uptake of the two compounds might not be identical. I n view of this, and because we know of no other study of peptide absorption following several dietary alterations, we have investigated the effects of different diets on the rates of absorption of methionine and dimethionine.Newey & Smyth (1959,1960,1962) first showed that mucosal uptake of dipeptides, with cellular hydrolysis, occurred in the small intestinc of the rat and dog. Studies of relative absorption rates of amino acids and small peptides and investigations of defects in intestinal amino acid transport have now shown that mucosal uptake of small peptides occurs in many mammalian species, including man (Matthews,

I. Yudkin's (1967) questionnaire on the dietary intake of sugar was given to 41 j businessmen for self-administration.2. The results showed an inverse relationship between sugar intake and relative weight (actual weight as a percentage of expected weight for height and age) and additional evidence suggests a direct relationship between sugar intake and adequate exercise.3. The statement that 'sugar was restricted' was shown to be a €actor of considerable importance affecting the reported level of sugar intake and should be taken into account when comparing different series.4. The positive association between cigarette smoking and mean sugar consumption in this series was due to the low-sugar intake of ex-smokers.5 . In future studies on the role of sucrose in the aetiology of ischaemic disease, both smoking habits and levels of activity should be recorded.

1. Though mucosal uptake of peptides plays an important part in protein absorption, little is known about the site of maximal absorption of peptides in the small intestine. This paper reports an investigation of the characteristics of absorption and hydrolysis of L-methionyl-L-methionine (Met-Met) and glycylglycine (Gly-Gly) by tied loops along the length of the small intestine of the rat, and those of absorption of the equivalent L-methionine (Met) and glycine (Gly).2. Absorption of Met-Met, or a mixture of Met-Met and Met, was maximal in the proximal half of the small intestine, whereas absorption of Met was maximal in the distal half. Absorption of Met-Met was greater than that of the equivalent Met, especially in the proximal small intestine. In most sites, absorption of a mixture of Met-Met and Met was not significantly different from that of the equivalent Met-Met. Absorption of Met was not increased by raising its concentration from 100 to 200 ,umol/ml, but addition of Met-Met (50 ,umol/ml) produced a large increase in absorption, indicating that absorption of Met from Met-Met is independent of that from free Met. During absorption of Met-Met, large amounts of free Met appeared in the intestinal lumen. Most of this resulted from intralumen hydrolysis. The hydrolytic ability of mucosal homogenates was several times greater than that required to hydrolyse the Met-Met disappearing from the lumen during absorption.3. The sites of maximal absorption of Gly-Gly, Gly and a mixture of Gly-Gly and Gly, were all in the proximal half of the intestine near the mid-point. Absorption of Gly-Gly was greater than that of the equivalent Gly, especially in the proximal sites. In several sites, there was no significant difference between absorption of a mixture of Gly-Gly and Gly and that of the equivalent Gly-Gly. During absorption of Gly-Gly, the amounts of free Gly appearing in the lumen were small except in the two most distal sites. Most of the free Gly resulted from back-diffusion from the mucosa. The hydrolytic ability of mucosal homogenates was barely adequate to hydrolyse the Gly-Gly disappearing from the lumen during absorption. 4.The results suggest that there is no real discrepancy between the site of maximal absorption of protein digestion products from tied loops of small intestine and that of their absorption in the intact animal. They indicate that absorption of Met and Met-Met involves independent mechanisms, and confirm previous evidence that the capacity of the intestine to absorb mixtures of peptides and amino acids is greater than its capacity to absorb amino acids alone.