Absorption of protein digestion products: a review.

Each major phase in the evolution of our present concept of the absorption of proteins and their digestion products has been initiated by an improvement in analytical techniques or experimental methods. Before 1900, it was thought that the final products of protein digestion were proteoses and peptones, and it seemed likely that proteins were absorbed in these forms. Then Cohnheim (1901) discovered an intestinal enzyme, 'erepsin', that catalysed the hydrolysis of these larger protein breakdown products to amino-acids. This was followed by the demonstration that amino-acids were present in the small intestine during protein digestion (Kutscher and Seemann, 1901; Abderhalden, K6r6sy, and London, 1907), that animals could live on diets containing only hydrolysed protein (Loewi, 1902; Henderson and Dean, 1903) and could utilize amino-acids given intravenously (Buglia, 1912), and that there was a rise in the non-protein nitrogen of the blood during the absorption of protein, protein hydrolysates, or amino-acids (Cathcart and Leathes, 1906; Folin and Denis, 1912). These observations suggested that proteins were absorbed from the gut and transported to the tissues as amino-acids, but since the analytical methods then available were not sufficiently specific to show unequivocally the presence of free amino-acids in the bloodstream, it was possible to maintain that amino-acids might be synthesized into protein while passing through the intestinal wall and reach the tissues mainly in this form (Abderhalden, 1912). In 1912, Van Slyke and Meyer, using the recently developed nitrous acid method, showed that there was a large rise in the amino-nitrogen of mesenteric and peripheral blood during the absorption of alanine and after feeding protein, and investigated the metabolic fate of absorbed amino-acids (Van Slyke and Meyer, 1912; 1913). Abel, Rowntree, and Turner (1914) obtained free amino-acids from the blood by vividialysis, and showed that they increased after a protein meal. This work laid the foundation for the theory that protein was completely hydrolysed within the lumen of the gut, and that the constituent amino-acids were absorbed into the bloodstream by simple diffusion (e.g., Verzar and McDougall, 1936). This theory, though based on evidence that is now seen to be incomplete (e.g., Dent and Schilling 1949; Fisher, 1954) seemed adequate to explain nearly all the older observations and dominated the field for many years. Further advances began in 1951, when it was shown by means of stereochemically specific methods that the L-isomers of many amino-acids were preferentially absorbed, which could not readily be explained if absorption were by simple diffusion. The development of techniques for studying absorption by isolated intestine in vitro made it possible to show that L-amino acids were actively transported by the small intestine, and since this time there has been great progress in knowledge of the mechanisms of absorption of protein digestion products. This paper gives an account of modern views on this subject and includes a brief description of the experimental methods which have contributed most to advances in the field.