Absorption and malabsorption of glycine and glycine peptides in man.

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 …