Sulfated lipids as inhibitors of pancreatic trypsin and chymotrypsin in epithelium of the mammalian digestive tract.

Cholesterol sulfate and I3SO3-GalCer, which were commonly contained in the epithelia of mammalian digestive tracts, were found to inhibit the activities of typical digestive enzymes, pancreatic trypsin and chymotrypsin, but steroid sulfates, gangliosides and the other membrane constituents did not show any inhibitory activity. The preincubation of trypsin with I3SO3-GalCer at 37 degrees C for 10min was necessary to inhibit the activity of trypsin, but cholesterol sulfate showed its inhibitory activity without preincubation. Sulfated lipid-treated enzyme gave the same Km as and lower Vmax than those of the original enzymes. Also, both sulfated lipids inhibited pronase from Streptomyces griseus, but not lysyl endopeptidase from Achromobacter lyticus. These findings indicate that cholesterol sulfate and I3SO3-GalCer in the digestive tract function as epithelial inhibitors to prevent tissue injury by endogenous and exogenous proteases.