Two potent competitive inhibitors discriminating α-glucosidase family I from family II

The inhibition kinetics for isoacarbose (a pseudotetrasaccharide, IsoAca) and acarviosine-glucose (pseudotrisaccharide, AcvGlc), both of which are derivatives of acarbose, were investigated with various types of alpha-glucosidases obtained from microorganisms, plants, and insects. IsoAca and AcvGlc, competitive inhibitors, allowed classification of alpha-glucosidases into two groups. Enzymes of the first group were strongly inhibited by AcvGlc and weakly by lsoAca, in which the K-i values of AcvGlc (0.35-3.0 PM) were 21 - to 440-fold smaller than those of lsoAca. However, the second group of enzymes showed similar Ki values, ranging from 1.6 to 8.0 muM for both compounds. This classification for alpha-glucosidases is in total agreement with that based on the similarity of their amino acid sequences (family I and family II). This indicated that the alpha-glucosidase families I and II could be clearly distinguished based on their inhibition kinetic data for lsoAca and AcvGlc. The two groups of alpha-glucosidases seemed to recognize distinctively the extra reducing-terminal glucose unit in IsoAca. (C) 2004 Elsevier Ltd. All rights reserved.