Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease
TL;DR: 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.
Abstract: A severely affected case of Hartnup 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, β-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.
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01 Feb 1985
TL;DR: It now appears certain that two major mechanisms are involved in the absorption of the luminal products of protein digestion: transport of liberated free amino acids by group specific active amino acid transport systems, and uptake of unhydrolysed peptides by mechanisms independent of the specific amino acid entry mechanisms.
Abstract: Although it has become clear that brush-border hydrolysis, and consequent utilization of the monosaccharide transport system, is the predominant method of absorption of the luminal products of carbohydrate digestion in man, it now appears certain that two major mechanisms are involved in the absorption of the luminal products of protein digestion: ( I ) transport of liberated free amino acids by group specific active amino acid transport systems, and (2) uptake of unhydrolysed peptides by mechanisms independent of the specific amino acid entry mechanisms.
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Cites background from "Studies on intestinal absorption of..."
...Despite these transport defects the ‘affected’ amino acids have been shown to be absorbed normally or near normally when presented to the mucosa in the form of homologous or mixed dipeptides (Navab & Asatoor, 1970; Asatoor et al. 197oa,b, 1972; Hellier et al. 19726; Silk et al. 1 9 7 5 ~ ) ....
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TL;DR: This manuscript will focus on the physical and metabolic barrier functions of the intestinal mucosa, the structural features of peptides which influence their passive diffusion and carrier-mediated transport, including efflux mechanisms, and various approaches used to prevent enzymatic degradation of the peptides and increase their permeability across the intestine mucosa.
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129 citations
TL;DR: It is suggested that whereas normal subjects absorb essential amino acids by a dual mechanism of mucosal uptake of free amino acids and oligopeptides, nutrition in Hartnup disease is largely dependent on uptake of oligopes containing the amino acids affected by the intestinal transport defect of the disease.
Abstract: The results of oral tolerance tests of two dipeptides and of their constitutent 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. Results of experiments on absorption and hydrolysis of the two peptides in the rat small intestine are also reported. It is suggested that whereas normal subjects absorb essential amino acids by a dual mechanism of mucosal uptake of free amino acids and oligopeptides, nutrition in Hartnup disease is largely dependent on uptake of oligopeptides containing the amino acids affected by the intestinal transport defect of the disease.
120 citations
TL;DR: The chapter discusses the intralumen and brush border hydrolysis of proteins and peptides , the active uptake of small peptides by the absorptive cells, the effects of peptides on intestinal transport of Na + and water, competition for mucosal uptake among peptides, and the kinetics of intestinal absorption of peptide.
Abstract: Publisher Summary This chapter deals with the transmembrane transport of small peptides in animals, in microorganisms, and in higher plants. Active transmembrane transport of small peptides is a mechanism of very wide distribution in nature and is of major biological importance. The main characteristics of peptide transport in animal intestine, the scutellum of germinating barley, a yeast, and in Escherichia coli (E. coli), are summarized in a tabulated form. The chapter discusses the intralumen and brush border hydrolysis of proteins and peptides , the active uptake of small peptides by the absorptive cells, the effects of peptides on intestinal transport of Na + and water, competition for mucosal uptake among peptides, and the kinetics of intestinal absorption of peptides. The general features of nutritional utilization of peptides by microorganisms, the nature of the microbial cell surface and membrane location of peptide permeases, the methods for studying peptide transport, and the peptide transport in bacteria and other microorganisms are also presented in the chapter. Various possible physiological advantages of transmembrane transport of small peptides are reviewed. Peptide uptake, as opposed to the uptake of free amino acids, might reduce the energy requirement for the transport in more than one way. One of these ways is that if peptides entering the cell are rapidly hydrolyzed, the peptide concentration within the cell may be maintained at a lower level than that outside it. In such a case, peptides could enter the cell by a process of facilitated diffusion, no expenditure of metabolic energy being required.
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343 citations
TL;DR: A method to assess the relative amounts of the -SH and the -S-S- forms of the amino acid in plasma to know whether both forms are present is of particular importance in the study of excretion of amino acids by the kidney.
Abstract: Studies on the amino acid content of physiological fluids have usually been carried out under conditions that would permit any cysteine present to be oxidized to cystine prior to analysis. Consequently, little quantitative information has been obtained concerning the relative amounts of the -SH and the -S-S- forms of the amino acid in plasma. To know whether both forms are present is of particular importance in the study of excretion of amino acids by the kidney. Cystine is an amino acid which appears in abnormal quantities in the urine in several pathological conditions (1). Failure of tubular reabsorption has usually been invoked to explain this fact (2), an explanation which tacitly assumes that it is cystine (the -S-S- form) not cysteine (the -SH form) that is circulating in the blood and is cleared by the kidney. If cysteine were to be the predominant form normally circulating, oxidation to cystine in the kidney would be required in order to account for the excretion of the disulfide in the urine. Fujita and Numata (3) and Smith and Tuller (4) have reported the presence of cysteine in blood. Another observation which could bear on the subject is that of Brand, Cahill and Harris (5) who showed that the amount of cystine in the urine of a cystinuric subject rose after feeding cysteine and methionine, but not after the ingestion of cystine, the sulfur of which appeared almost exclusively as urinary sulfate. With these thoughts in view, a method has been
212 citations
TL;DR: The 'glycine tolerance test', an oral dose of glycine followed by analysis of peripheral blood samples, was first used for investigating amino acid absorp- tion more than 30 years ago by Heath and Fullerton, who concluded that the test gave 'no useful information regarding the rate of absorption from the gastrointestinal tract'.
Abstract: The 'glycine tolerance test', an oral dose of glycine followed by analysis of peripheral blood samples, was first used for investigating amino acid absorption more than 30 years ago by Heath and Fullerton (1935), who, though they did not investigate any cases of unequivocal malabsorption, concluded that the test gave 'no useful information regarding the rate of absorption from the gastrointestinal tract'. Though the test has been used sporadically ever since in the investigation of gastrointestinal disease, particularly tropical sprue, pancreatic insufficiency, and intestinal resections The published normal values for both these tests are based on few observations, and in several cases these are quite inadequately reported, only mean values being given. Even Butterworth et al, in their investigation of the glycine test in tropical sprue, which is the best account of it, report only nine normal curves. A major disadvantage of the test as usually carried out has been methodological: the colorimetric estimation of amino-acid nitrogen (Folin, 1922) is relatively non-specific, while both the standard gasometric estimations of alpha-amino nitrogen (Hamilton and Van Slyke, 1943), and specific estimation of glycine (Alexander, Landwehr, and Seligman, 1945) are technically fairly difficult, time-consuming, and unsuited to the estimation of numerous samples. The advent of rapid colorimetric ninhydrin methods for plasma alpha-amino nitrogen (a-NH2N), which are nearly as specific as the gasometric determination, and of a more convenient method for specific glycine estimation, combined with recent advances in our knowledge of the physiology of absorption of protein digestion products (Crane, 1961; Matthews and Laster, 1965a), which have radically altered older views, suggested a re-investigation of the glycine tolerance test. The object of the present work was to do this, to investigate the absorption of glycylglycine (diglycine) and glycyl-glycylglycine (triglycine) under similar conditions, and to apply tests of free and peptide glycine absorption in various gastrointestinal disorders. The investigation of peptide absorption in man seemed of particular interest (1) because recent investigations in animals have suggested that small peptides are not hydrolysed mainly in the intestinal lumen, as previously supposed, but transported into the cells of the intestinal mucosa and hydrolysed within them, subsequently being transported onwards and entering the blood as free amino acids (2) because of suggestions that intestinal peptidases might be deficient in idiopathic steatorrhoea. Such deficiency might be either (a) primary deficiency of one particular (hypothetical) peptidase, allowing accumulation of some toxic breakdown product of gliadin and implicated in the …
145 citations