Acarbose and 1-deoxynojirimycin inhibit maltose and maltooligosaccharide hydrolysis of human small intestinal glucoamylase-maltase in two different substrate-induced modes

The inhibition of the glucoamylase-maltase-catalyzed maltose and maltooligosaccharide hydrolysis by acarbose and 1-deoxynojirimycin has been demonstrated. Acarbose and 1-deoxynojirimycin act as potent competitive inhibitors with K-i = 0.8 mu M for the hydrolysis of maltose and with K-i values of 0.4 and 0.3 mu M, respectively, for the hydrolysis of maltooligosaccharides. In a previous work (Gunther et al., Arch. Biochem. Biophys. 327, 295-302, 1996) using maltitol and maltobionate as inhibitors we were able to discriminate two different binding modes for glucoamylase-maltase: a maltose and an oligosaccharide binding mode. Here we found that structurally quite different substances, namely, the pseudotetrasaccharide acarbose and the monomeric glucose analog 1-deoxynojirimycin, act as competitive inhibitors for maltose and maltooligosaccharide hydrolysis, The K-i values for all used maltooligosaccharides are nearly equal, but for maltose hydrolysis the K-i values are significantly higher by a magnitude factor of two. The differences concerning K-i values can be explained by means of the two-binding-mode model. (C) 1997 Academic Press.