Inhibition spectra of the human pancreatic endopeptidases

The present work describes the effect of seven naturally occurring proteinase inhibitors on the human pancreatic endopeptidases cationic trypsin, anionic trypsin, chymotrypsin I, chymotrypsin II, and protease E (an elastase-like protease). The inhibitors tested in order of their decreasing effectiveness were alpha-1-proteinase inhibitor (alpha-1-antitrypsin), lima bean trypsin inhibitor, soybean trypsin inhibitor, Bowman-Birk (soybean) inhibitor, Kunitz pancreatic trypsin inhibitor, porcine Kazal inhibitor, and chicken ovomucoid. The human trypsins demonstrated a higher degree of susceptibility to these inhibitors than did the chymotrypsins while human protease E showed remarkably little inhibition by any of these naturally occurring proteinase inhibitors except for alpha-1-proteinase inhibitor. The contribution of each of these proteolytic enzymes to the total proteolytic activity of crude extracts was also investigated using specific active-site directed reagents. These studies revealed that the trypsins constituted approximately 35% of the proteolytic activity while the chymotrypsins represent approximately 32% of the total proteolytic activity. Human protease E and possibly human pancreatic elastase are responsible for approximately 21% of this activity as measured on crude pancreatic extracts.