S U M MARY Serum concentrations of ,B-alanine and L-histidine are compared in five normal adults after ingestion of the dipeptide carnosine (/-alanyl-L-histidine) and after equivalent amounts of the constituent free amino acids. The results indicate that absorption is significantly more rapid after the ingestion ofthe amino acids than after the dipeptide. The use of the test in a case of Hartnup disease suggests that carnosine is taken up by intestinal cells as the dipeptide, but subsequent hydrolysis and delivery of the constituent amino acids to the portal blood is a slower process than transport of the free amino acids themselves.

SUMMARY The results of oral tolerance tests of two dipeptides and of their constituent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide.

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.

SUMMARY A severely affected case ofHartnup disease is reported,where the patient responded rapidly to nicotinamide. This supports the view that all the clinical features, except reduced stature from general nutritional defect, are secondary to tryptophan and nicotinamide deficiency rather than to an unknown toxic factor. Severe malabsorption of both tryptophan and phenylalanine was demonstrated. The dipeptide carnosine was absorbed normally whereas when the two constituent amino acids, f-alanine and L-histidine, were ingested, absorption of the former was normal but that of the latter was grossly defective. The suggestion is advanced that in cases of Hartnup disease protein nutrition is maintained by intestinal uptake of amino acids as oligopeptides rather than as free amino acids. By contrast, both modes of absorption are probably important in normal subjects. Radiology of the small intestine is abnormal in Hartnup disease when a large amount of protein is admixed with the barium meal.Hartnup disease is an autosomal recessive hereditary disease which manifests clinically with a pellagrous rash and neuropsychiatric abnormalities and is associated with a diagnostic type of aminoaciduria. Impaired transport of certain neutral amino acids has been demonstrated in the proximal renal tubules (Cusworth

These observations suggest that the rate of nosocomial pneumonia is not increased in patients in the intensive care unit who receive prophylaxis with cimetidine to prevent stress ulcer bleeding.