Intracellular proteolysis of pancreatic zymogens

B,andchymotrypsinogen 2)totheir active forms. Thus, this conversion maybeageneralized phenomenon ofpancreatic zymogens. Theconversion isdetected within tenminutes oftreatment andisnotassociated withchanges inacinar cell morphology; ithas beenpredicted thatthelysosomal thiol protease, cathepsin B,mayinitiate this conversion. Small amounts ofcathepsin Barefound inthesecretory pathway, andcathepsin Bcanactivate trypsinogen invitro; however, exposure ofacini toathiol protease inhibitor (E64) didnotblock this conversion. Conversion wasinhibited bytheserine protease inhibitor, benzamidine, andby raising theintracellular pH,using chloroquine ormonensin. Thislimited proteolytic conversion appears torequire alowpHcompartment andaserine protease activity. After long periods of treatment (60minutes), theamountsoftheactive enzymeformsbegantodecrease; this observation suggested that theactive enzymeforms werebeing degraded. Treatment ofacini withE64reduced this late decrease inactive enzymeforms, suggesting that thiol proteases, including lysosomal hydrolases, maybeinvolved inthedegradation oftheactive enzymeforms. Thesefindings indicate that pathways forzymogen activation aswell asdegradation ofactive enzymeforms arepresent within thepancreatic acinar cell.