Proteins

Proteins 
Unlike other digestive enzymes, those with proteoly­tic activity are generally secreted in an inactive form. As a result, the gastric initiation of protein breakdm.vrJ. by pep­sins depends on activation of pepsinogen (the inactive form of pepsin) by Hel or by small amounts of pepsin itself. The mixture of polypeptides (known as proteoses  pep tones, and oligopeptides) produced by gastric digestion is further degraded by pancreatic proteasess, which principally function in the lumen of the small intestine. Trypsin, secreted as trypsinogen, is activated by intestinal enterokinase or by trypsin itself, depeuding on the pH of the medium. Trypsin also converts chymotryp­sinogen to its active form. Both of these enzymes are endopeptidases and can degrade either intact proteins or polypeptides into smaller units, the major difference in their action being the specificity of the peptide bonds cleaved by each. Appreciable amounts of intact protein enter the intestine daily from the intestinal secretions and desquamated epithelial cells and are digested along with the dietary proteins. Thus gastric digestion is not essential for the use of protein in the body.
Though much of protein degradation by pancreatic proteases takes place in the lumen of the digestive tract, some polypeptide hydrolysis is also believed to occur a t the  brushborder by adsorbed enzymes. Pancreatic juice also contains exopeptidases, mostly carboxypeptidases, which spli t off amino acids from the carboxy terminus of peptides.
The digestive process in the intestinal lumen pro­duces a mixture of amino acids and oligopeptides that may be very complex, as one can envision from the many possible amino acid sequences that occur in proteins. Further cleavage of oligopeptides into dipeptides and amino acids results from the action of intestinal pep­tidases located on the brushborder. Though only free amino acids are found in the portal blood after protein ingestion, a significant proportion of protein is believed to leave the lumen as small peptides, which are then hydro­lyzed by mucosal peptidases either in the brushborder or intracellularly. Present experimental evidence favors both sites, as shown in the scheme of protein absorption proposed by Matthews.
Dipeptides appear to be hydrolyzed mostly intra­cellularly, whereas membrane hydrolysis predominates for tetra and larger oligopeptides, and extensive hydroly­sis of tripeptides takes place at both sites.
The transport mechanisms for amino acids, and more recently for peptides, have been the subject of in ten­sive study. According to presently available evidence the transport offree amino acids from the lumen to the portal capillaries is accomplished by carrier mediated processes that seem to be sodium and energy dependent for most amino acids. Several distinct transport mechanisms seem to exist, each of which is active with a group of amino acids with similar properties. It is also likely that individ­ual amino acids may use more than one transport system.
Competi tion benveen amino acids of the same trans­port group has been demonstrated. This competition is avoided if the same amino acids are present as small peptides.These observations suggest the existence of separate transport systems for uptake of peptides and amino acids into the epithelial cell. Other lines of evidence also support this view.
Contrary to a view long held, the absorption of ami no acids from and tripeptides is more rapid than that from the equivalent amino acid mixtures. Similarly, in some diseases involving severely impaired absorption of free amino acids due to a defective transport system (Hartnup disease, cystinuria) the same amino acids can be absorbed when they are part of small peptides.The capacity to absorb peptides independently of amino acid absorption explains the relatively good nutritional status and freedom from intestinal disturbances of patients with defective amino acid transport.
Because various pathologic conditions appear to af­fect peptide absorption less than amino acid absorption, the use of a mixture of peptides may be mos t beneficial in the treatment of protein deficits in patients with problems of maldigestion or malabsorption from diverse causes.
In contrast to the pancreatic exopeptidases, the mucosal enzymes are aminopeptidases. Studies have shown that mucosal peptidase activity responds to changes in the level of dietary protein, due mainly to the adaptive response of the brushborder enzymes.