Endopeptidase activity results in the formation of peptides, which are then acted upon by pancreatic ectopeptidases. These enzymes cleave single amino acids from the end of a peptide chain. The specific ectopeptidases present in pancreatic juice are either carboxypeptidase A, which targets neutral amino acids, or carboxypeptidase B, which targets basic amino acids located at the C-terminus. Hence, the digestion of a protein meal by gastric and pancreatic secretions produces neutral and basic amino acids, as well as short peptides with acidic amino acids at their C-termini, making them resistant to carboxypeptidase A or B (Fig. 30.13).

The brush border is the site of the final phase of protein digestion. Mature enterocytes express various peptidases on their brush borders, including amino-peptidases and carboxypeptidases. These enzymes generate products that are suitable for uptake across the apical membrane (see Fig. 30.11). It is important to note that despite the presence of active proteolytic enzymes, some dietary peptides are resistant to hydrolysis, either partially or completely. Peptides containing proline or glycine, in particular, are digested slowly. Fortunately, the intestine can absorb short peptides in addition to single amino acids. Although the majority of peptides taken up into the enterocyte remain intact, they undergo a final stage of digestion in the cytosol of the enterocyte to release their constituent amino acids for use within the cell or elsewhere in the body (Fig. 30.14). However, some di- and tripeptides may also be transported into the blood without further breakdown.

Fig. 30.13 illustrates the luminal digestion of peptides resulting from partial proteolysis in the stomach. Carboxypeptidase A acts on peptides with C-terminal neutral amino acids, while chymotrypsin and elastase act on larger peptides. Carboxypeptidase B targets peptides with C-terminal basic amino acids, and short peptides containing free neutral and basic amino acids are also present.

Fig. 30.14 depicts the uptake of a wide variety of dipeptides and tripeptides across the brush border membrane through the action of the proton-coupled symporter known as peptide transporter 1 (PepT1). The protongradient necessary for this process is created by the action of sodium/hydrogen exchangers (NHEs) in the apical membrane. While most peptides are digested in the cytosol to release their constituent amino acids for export, a small proportion may be exported intact.

The body possesses plasma membrane transporters capable of facilitating the uptake of water-soluble products resulting from protein digestion. Due to the large number of amino acids, there are several specific transporters involved (see Figs. 30.11 and 30.14). Amino acid transporters are clinically significant as the absence of specific transporters in various genetic disorders can lead to reduced ability to transport the corresponding amino acid(s). However, such mutations often have no significant nutritional implications as the amino acid in question can be assimilated through other transporters with overlapping specificity or in the form of peptides. Nonetheless, the possibility of pathology in other organ systems cannot be ruled out.
amino acids. The peptides that result from endopeptidase activity are then acted on by pancreatic ectopeptidases. These enzymes cleave single amino acids from the end of a peptide chain, and those present in pancreatic juice are specific for either neutral (carboxypeptidase A) or basic (carboxypeptidase B) amino acids situated at the C-terminus. Thus the products that result after digestion of a protein meal by gastric and pancreatic secretions include neutral and basic amino acids, as well as short peptides that have acidic amino acids at their C-termini and thus are resistant to carboxypeptidase A or
B (Fig. 30.13
The final phase of protein digestion takes place at the brush border. Mature enterocytes express a variety of peptidases on their brush borders, including both amino-peptidases and carboxypeptidases that generate products suitable for uptake across the apical membrane (see
Fig.
30.11 ). However, it should be noted that even with the substantial complement of active proteolytic enzymes, some dietary peptides are either relatively or totally resistant to hydrolysis. In particular, peptides containing either proline or glycine are digested very slowly. Fortunately the intestine can take up short peptides in addition to single amino acids. The majority of peptides taken up into the enterocyte in their intact form are then subjected to a final stage of digestion in the cytosol of the enterocyte to liberate their constituent amino acids for use in the cell or elsewhere in the body (Fig. 30.14 ). However, some di-and tripeptides may also be transported into the blood in their intact form.
•Fig. 30.13 Luminaldigestionofpeptidesresultingfrompartialproteolysisinthestomach.AA,aminoacid.(RedrawnfromBarrettKE.Gastrointestinal Physiology. NewYork:McGraw-Hill;2006.)Peptide with C-terminal neutral AA Carboxypeptidase AChymotrypsin Elastase Large peptides Trypsin Peptide with C-terminal basic AA Short peptides free neutral and basic AAs SerArg Carboxypeptidase B Ser Arg •Fig. 30.14 Awidevarietyofdipeptidesandtripeptidesaretakenupacrossthebrushbordermembranebytheproton-coupledsymporterknownaspeptide transporter 1 (PepT1).Theprotongradientiscreatedbytheactionofsodium/hydrogenexchangers(NHEs)intheapicalmembrane.Peptidesarelargelydigestedinthecytosoltotheirconstituentaminoacidsforexporttothebody,butasmallproportionmaybeexportedintact.
Uptake of Peptides and Amino Acids
The body is also endowed with a series of plasma membrane transporters capable of promoting uptake of the water-soluble products of protein digestion. Given the large number of amino acids, there is a relatively large number of specific transporters (see
Figs. 30.11 30.14 ). Amino acid transporters are of clinical interest because their absence in a variety of genetic disorders results in diminished ability to transport the relevant amino acid or acids. However, such mutations are often clinically silent, at least from a nutritional standpoint, because the amino acid in question can be assimilated by other transporters with overlapping specificity or in the form of peptides. This does not rule out the possibility of pathology in other organ systems in