blood analysis

Trypsin and chymotrypsin

Trypsin and chymotrypsin are two key enzymes in the digestion of dietary proteins. Both are produced and secreted as zymogens, ie in an inactive form, by the pancreas; the zymogen precursor of trypsin is called trypsinogen, while that of chymotrypsin is called chymotrypsinogen.

Trypsin and chymotrypsin belong to the large family of proteolytic enzymes (involved in protein digestion) and to the endopeptidase subgroup. These substances - including gastric pepsin and pancreatic elastase - attack peptide bonds within the amino acid chain, giving rise to smaller molecular fragments. The enzymes belonging to the second group, that of exopeptidases, complete the work of trypsin and chymotrypsin, detaching individual amino acids from the ends of the peptide chain; Pancreatic carboxypeptidases (A1, A2 and B, which attack the carboxyl end) belong to this family, but also aminopeptidases (which attack the aminoterminal end) and dipeptidases, both produced and secreted by the mucosa of the small intestine. Some carboxypeptidases, similar to those seen for trypsin (trypsinogen) and chymotrypsin (chymotrypsinogen), are secreted by the pancreas in an inactive form. In all three cases the enzyme involved in the enzymatic activation process is the enteropeptidase, a protein produced and secreted by the cells of the duodenal mucosa; more specifically, the enteropeptidase is specific for trypsinogen, which once converted into trypsin also activates the other proteolytic enzymes, including trypsinogen itself.

The functional differences between trypsin and chymotrypsin simply concern their specificity, that is the ability to recognize and break down only the bonds formed by well-defined amino acids. Trypsin intervenes mainly on the peptide bonds that engage basic amino acids (such as arginine and lysine), while chymotrypsin hydrolyzes mainly bonds involving tyrosine, phenylalanine, tryptophan, leucine and methionine.

Thanks to the various proteolytic enzymes, with the contribution of gastric acidity, dietary proteins - originally formed by several tens of amino acids - are broken down into dipeptides, tripeptides and free amino acids, all easily absorbable substances that from the capillaries of the intestinal mucosa come transported to the liver.

Trypsin and chymotrypsin in faeces

The determination of chymotrypsin and trypsin in faeces is used, and was especially so in the past, as an indirect test of the functional capacity of the exocrine pancreas. If something does not work properly at this gland level, it is logical to expect a reduced synthesis of trypsin and chymotrypsin, which will also be deficient in faeces. The test has good sensitivity, but is burdened by the real risk of false positives and false negatives. The use of laxatives, for example, decreases the concentration of enzymes in the fecal material, while the intake of digestive pancreatic extracts (such as pancreatin) or vegetables (eg pineapple stalk, papaya, papain and bromelain) cause false negative results. Also the intestinal bacterial flora slightly influences the quantity of trypsin and chymotrypsin that arrive unaltered in the faeces; for this reason the use of antibiotics can produce false negatives; on the contrary, in the presence of diverticulosis and other conditions that favor bacterial proliferation, false positive results can be recorded.

A classic application of trypsin and chymotrypsin dosage in faeces is the detection of pancreatic insufficiency in patients with cystic fibrosis. One of the consequences of this disease is the impairment of normal transport of trypsin and other digestive enzymes from the pancreas to the duodenum; for this reason, at birth, the faeces of the child with cystic fibrosis are particularly compact, to the point of causing an intestinal obstruction. As a result, particularly small amounts of chymotrypsin and trypsin are recorded in meconium.