Figure 2. The intrapancreatic activation of trypsinogen into active trypsin is a process regulated by at least two distinct mechanisms. 1. The PSTI (pancreatic secretory trypsin inhibitor), now referred as to SPINK1 (serine protease inhibitor, Kazal type 1), is synthesized with trypsinogen in a ratio of 1:5, and can inhibit the activation of trypsinogen by trypsin. 2. Trypsin itself by means of a feed-back mechanism can inactivate trypsin and trypsin-like enzymes by hydrolyzing the connecting chain between the two globular domains of the trypsin. Interestingly, in patients with hereditary pancreatitis, trypsin cannot be inactivated because of a mutation (R122H) in the connecting chain making its hydrolysis impossible.