trypsinogeeni

Trypsinogen is the inactive precursor, or zymogen, of the digestive enzyme trypsin. In humans it is produced mainly by pancreatic acinar cells and secreted into the small intestine as part of pancreatic juice. The activation of trypsinogen to trypsin occurs at the duodenal brush border, where the enzyme enteropeptidase (enterokinase) cleaves a specific activation peptide. Once activated, trypsin begins protein digestion and also activates other pancreatic zymogens, including chymotrypsinogen, procarboxypeptidases, and, indirectly, pancreatic lipase cofactors, amplifying digestive processes.

Structure and biochemistry: Trypsinogen is a single polypeptide that contains an N-terminal activation peptide. Activation alters the conformation of the catalytic triad of trypsin, enabling proteolysis. As trypsin activity increases, there is potential for autodigestion if the system is not properly regulated, which is normally prevented by endogenous inhibitors.

Genetics and clinical relevance: In humans, two main trypsinogen genes encode isoforms: PRSS1 (trypsinogen 1) and PRSS2 (trypsinogen 2). Mutations in PRSS1 that promote premature activation or increased stability of trypsin can predispose to hereditary pancreatitis. Genetic and environmental factors, including inhibitors such as SPINK1, influence disease risk. PRSS2 mutations are less clearly associated with pancreatitis.

Diagnostic and physiological role: Trypsinogen levels are used as biomarkers of pancreatic function. Elevated serum trypsinogen can indicate pancreatic injury or inflammation, while reduced activity may reflect pancreatic insufficiency. Immunoreactive trypsinogen (IRT) is measured in newborn screening for cystic fibrosis, where high levels prompt confirmatory testing. In normal digestion, regulated activation ensures efficient protein digestion without tissue damage.