Inhibition of some hepatic lysosomal glycosidases by ethanolamines and phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside

The hepatic lysosomal glycosidases alpha-glucosidase and beta-glucuronidase were inhibited in vitro and in vivo by mono- and diethanolamines. The in v ivo inhibition is dose dependent and occurs at a value less than LD50. Phen yl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside inhibited alpha-glucos idase both in vitro and in vivo. The treatment of the enzymes in vitro by e thanolamine exhibited a reversible inhibition of the mixed and competitive types for alpha-glucosidase and beta-glucuronidase, respectively. Diethanol amine showed a reversible inhibition of the competitive type for both enzym es. It is a potent inhibitor for beta-glucuronidase, in vitro, whose inhibi tion constant (K-i) is 5 x 10(-5) M. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta -D-glucopyranoside is a potent inhibitor only for hepatic alpha-glucosidase with a K-i value of 1.6 x 10(-5) M. The pattern of the pH dependence of en zymic activity was not affected by ethanolamine inhibition. The magnitude o f the inhibition of enzymes is dependent on the structure of the inhibitor. (C) 1999 Elsevier Science Ltd. All rights reserved.