SULFATED LIPIDS AS INHIBITORS OF PANCREATIC TRYPSIN AND CHYMOTRYPSIN IN EPITHELIUM OF THE MAMMALIAN DIGESTIVE-TRACT

Cholesterol sulfate and (ISO3)-S-3-GalCer, which were commonly contain ed in the epithelia of mammalian digestive tracts, were found to inhib it the activities of typical digestive enzymes, pancreatic trypsin and chymotrypsin, but steroid sulfates, gangliosides and the other membra ne constituents did not show any inhibitory activity. The preincubatio n of trypsin with (ISO3)-S-3-GalCer at 37 degrees C for 10min was nece ssary to inhibit the activity of trypsin, but cholesterol sulfate show ed its inhibitory activity without preincubation. Sulfated lipid-treat ed enzyme gave the same Km as and lower Vmax than those of the origina l enzymes. Also, both sulfated lipids inhibited pronase from Streptomy ces griseus, but not lysyl endopeptidase from Achromobacter lyticus. T hese findings indicate that cholesterol sulfate and (ISO3)-S-3-GalCer in the digestive tract function as epithelial inhibitors to prevent ti ssue injury by endogenous and exogenous proteases. (C) 1997 Academic P ress.