• Pancreatic enzymes (except amylase and lipase) are synthesized and secreted in an inactive form to protect the pancreas from autodigestion.
  • These proenzymes (zymogens) are activated by trypsin in the duodenal lumen.
  • Trypsinogen is converted into active trypsin by duodenal enterokinase.
• Activation cascade:
  • Trypsin can activate other trypsinogen molecules.
  • Even small amounts of trypsin can trigger this cascade.
• Protective mechanisms to limit premature trypsinogen activation:
  • Serine peptidase inhibitor Kazal-type 1 (SPINK1):
    • Secreted by pancreatic acinar cells.
    • Functions as a trypsin inhibitor, impeding prematurely activated trypsinogen molecules within the pancreas.
  • Trypsin self-inhibition:
    • Trypsin can cleave active trypsin molecules at a second site, rendering them inactive.
• Hereditary pancreatitis:
  • Rare disorder caused by mutations in the trypsinogen or SPINK1 gene.
  • Common mutation results in abnormal trypsin that is not susceptible to inactivating cleavage by trypsin.
  • Protective mechanisms are critical as small amounts of trypsinogen normally activate prematurely within pancreatic acini and ducts.
  • Failure of these mechanisms leads to recurrent acute pancreatitis.