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 Ki = 0.8 microM for the hydrolysis of maltose and with Ki values of 0.4 and 0.3 microM, respectively, for the hydrolysis of maltooligosaccharides. In a previous work (Günther 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 Ki values for all used maltooligosaccharides are nearly equal, but for maltose hydrolysis the Ki values are significantly higher by a magnitude factor of two. The differences concerning Ki values can be explained by means of the two-binding-mode model.
Breitmeier
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Zentrum Biochemie, Arbeitsbereich Enzymologie, Medizinische Hochschule Hannover, Germany.
Günther
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Heymann
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D017485:1-Deoxynojirimycin / Q000494:pharmacology*; D020909:Acarbose; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005936:Glucans / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006868:Hydrolysis; D007421:Intestine, Small / Q000201:enzymology*; D007700:Kinetics; D008320:Maltose / Q000031:analogs & derivatives / Q000378:metabolism*; D008956:Models, Chemical; D009844:Oligosaccharides / Q000378:metabolism*; D014312:Trisaccharides / Q000378:metabolism / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005936:Glucans; D065089:Glycoside Hydrolase Inhibitors; D009844:Oligosaccharides; D014312:Trisaccharides; C021705:maltooligosaccharides; D017485:1-Deoxynojirimycin; C031146:maltoheptaose; C008317:maltotriose; D008320:Maltose; C009819:maltotetraose; D020909:Acarbose