Trypsinogen is a zymogen or a proenzyme. Proenzymes are inactive precursors of enzymes. Trypsinogen is the inactive precursor of the digestive enzyme trypsin.
What is trypsinogen?
Trypsinogen is a so-called proenzyme. A proenzyme is a precursor of an enzyme. However, this precursor is inactive and must first be activated. Activation is carried out by proteases, the enzyme itself or as a function of pH values or chemicals. In its active form, trypsinogen is called trypsin. It plays an important role in digestion and here in particular in the cleavage of proteins. A deficiency of trypsinogen can lead to digestive disorders.
Function, effect, and tasks
Trypsinogen is produced by the pancreas. Production takes place in the exocrine part of the pancreas. The pancreas is the most important digestive gland in the human body. Together with trypsinogen, other digestive enzymes and proenzymes are produced here. Together with chymotrypsinogen and elastase, trypsinogen belongs to the protein-cleaving enzymes. They are also referred to as proteases. These substances, together with the enzymes for carbohydrate cleavage, the enzymes for fat cleavage and a bicarbonate-containing fluid, form the pancreatic secretion. Per day, the pancreas produces about one and a half liters of this digestive secretion. However, the exact amount and composition of the secretion released depends on the food consumed. For example, the more protein that has been eaten, the higher the proportion of protein-splitting enzymes. However, the secretion of trypsinogen is also controlled by parasympathetic and endocrine mechanisms. The hormones secretin and cholecystokinin (CCK) play a crucial role here.
Formation, occurrence, properties, and optimal values
Via the pancreatic ducts, trypsinogen enters the large pancreatic duct together with the rest of the pancreatic secretion. This opens into the small intestine. In the small intestine, trypsinogen is converted into its active form. For this purpose, a hexapeptide is cleaved from the proenzyme by an enterokinase. This produces the active digestive enzyme trypsin. Trypsin is an endopeptidase and cleaves proteins. More precisely, depending on the intestinal region, trypsin cleaves protein bonds with the basic amino acids lysine, arginine and cysteine. Under basic conditions, i.e. at a pH between seven and eight, trypsin works most effectively. These conditions are provided by the alkaline pancreatic secretion in the small intestine. However, trypsin has another task. It serves as an activator for other proenzymes. For example, it converts the proenzyme chymotrypsinogen into the active form chymotrypsin. However, the question remains why the pancreas does not produce trypsin directly, but first an inactive precursor. The answer is quite simple. If active digestive enzymes were already circulating in the pancreas, they would also already begin their work in the pancreas. The pancreas would thus digest itself. This process is also called autodigestion. It is found, for example, in acute pancreatitis.
Diseases and disorders
Acute pancreatitis is an inflammation of the pancreas. The most common cause of such dangerous inflammation is gallstones. When these travel from the gallbladder through the bile ducts, they often get stuck at the junction with the small intestine. In many people, the bile duct opens into the small intestine together with the pancreatic duct, so that if the bile duct becomes obstructed at this point, the pancreatic duct automatically becomes obstructed as well. As a result of this obstruction, the pancreatic digestive secretions back up into the small ducts. For reasons that are not yet fully understood, there is an early activation of the proenzymes. Thus, trypsinogen becomes trypsin, and chymotrypsinogen becomes chymotrypsin. The digestive enzymes perform their work in the pancreas and digest the pancreatic tissue. This results in tissue breakdown and severe inflammation. Acute pancreatitis begins suddenly with severe pain in the upper abdomen. The pain may radiate belt-like into the back and be accompanied by nausea and vomiting. There is accumulation of air in the abdomen, which, in connection with the characteristic defensive tension, leads to the phenomenon of rubber belly.If the walls of the pancreas are damaged to such an extent that pancreatic secretions leak into the abdominal cavity, other organs may also be affected. This can lead to sepsis. In severe courses, blue-green spots may be observed around the belly button (Cullen’s sign) or around the flanks (Grey-Turner’s sign). An increased serum concentration of trypsin can be detected in the laboratory. In pancreatic insufficiency, on the other hand, there is a deficiency of trypsinogen and thus also a deficiency of trypsin. The other digestive enzymes and proenzymes are also affected by the loss of pancreatic function. Pancreatic insufficiency usually results from previous inflammation. Chronic pancreatitis plays a particularly important role here. It is the result of chronic alcohol abuse in more than 80% of cases. However, pancreatic insufficiencies can also occur in cystic fibrosis, for example. Cystic fibrosis is a hereditary disease that affects the pancreas, lungs, liver and intestines. In particular, the glands of these organs are affected. The pancreatic secretion of patients suffering from cystic fibrosis is much more viscous than in healthy people. It clogs the pancreatic ducts, leading to inflammation. Due to the lack of digestive enzymes, pancreatic insufficiency primarily causes digestive problems. Those affected suffer from flatulence, bloating and diarrhea. Also typical are so-called fatty stools, which are caused by a lack of fat digestion. The stools then appear greasy, shiny and have a foul odor. Weight loss despite unchanged or even increased food intake is also characteristic.
