Protein Digestion and Absorption

About three-quarters of a century ago, Santayana wrote, "Those who cannot remember the past are condemned to repeat it." This somber dictum is splendidly illustrated by the history of the study of protein digestion and absorption over the same three-quarters of a century (12,13). This chapter begins with a summary of this history, since it provides a deeper understanding of the principles involved than a mere outline of present views accompanied by an account of the minutiae of recent advances in the field. By the late 19th century, it was understood that protein digestion was initiated by pepsin and continued by the proteolytic activity ("trypsin") of the pancreatic juice, the result of this digestion being "peptones", e.g., mixtures of polypeptides of moderate size with a proportion of dipeptides and free amino acids (17). Since peptones could not be demonstrated in the portal blood after protein meals, and for other reasons, it became widely believed that they were resynthesised to plasma proteins in the intestinal wall. This "hypothesis of resynthesis" received the powerful support of Abderhalden. The modern era in the study of protein absorption began at the turn of the century when a young medical graduate in the Department of Physiology in Heidelberg (a Department headed by Willy Kiihne, who had investigated and named trypsin) set himself the task of verifying the hypothesis of resynthesis. This young man was Otto Cohnheim; his findings were of such importance, and his career, which ended in tragedy, so interesting, that I wrote a short biography of him (14). What Cohnheim found was that extracts of the intestinal mucosa, far from synthesizing peptones into larger molecules, broke them down completely to free amino acids. Without this demonstration, further advances in the fields of protein absorption and metabolism would have been impossible. Cohnheim named the enzyme(s) responsible "erepsin" from a Greek root meaning "to break down" (4). At first, Cohnheim was unable to say whether erepsin acted within the absorptive cells or within the intestinal lumen: "Ob das Erepsin intracellular wirkt, Oder in das Darmlumen secernirt wird, kann ich noch nicht sagen". A year later, however, he was able to say— he had formed the view that erepsin was primarily an intracellular enzyme. It followed that peptides might be expected to enter the absorptive cells and