Inhibitory effect of pseudo-aminosugars on oligosaccharide glucosidases I and II and on lysosomal alpha-glucosidase from rat liver.
We examined the inhibitory effect of three pseudo-aminosugars (validamine, valienamine, and valiolamine), which were isolated from the broth of Streptomyces hygroscopicus, on the oligosaccharide-processing glucosidases I and II involved in glycoprotein biosynthesis in rat liver. Both glucosidases I and II were inhibited to the same extent by the pseudoaminosugars, and valiolamine had a more potent inhibitory activity than validamine or valienamine. A 50% inhibition of valiolamine was observed at 12 microM for glucosidase I and glucosidase II activities acting respectively on the substrates Glc3Man9GlcNAc2 and p-nitrophenyl alpha-D-glucopyranoside. Further, in order to investigate further the ability of valiolamine to inhibit glucosidase I, reaction products were analyzed by gel filtration on a Bio-Gel P-4 column. We also compared the inhibitory action of these pseudo-aminosugars on the acid alpha-glucosidase of rat liver lysosomes. They competitively inhibited the hydrolysis of both substrates, maltose and glycogen. Valiolamine again had a more potent lysosomal alpha-glucosidase inhibitory activity than the other two. The Ki values of valiolamine for the hydrolysis of maltose and glycogen were 8.1 and 11 microM, respectively. Valiolamine is a particularly effective inhibitor of oligosaccharide glucosidases I and II and of lysosomal alpha-glucosidase. Hence valiolamine might be useful as a research tool in investigations of carbohydrate metabolism.
Takeuchi
M
M
Department of Biochemistry, School of Pharmacy, Hokuriku University, Ishikawa.
Kamata
K
K
Yoshida
M
M
Kameda
Y
Y
Matsui
K
K
D000606:Amino Sugars / Q000494:pharmacology*; D000818:Animals; D002850:Chromatography, Gel; D053138:Cyclohexenes; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D065089:Glycoside Hydrolase Inhibitors; D006595:Hexosamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013302:Streptomyces / Q000378:metabolism; D000520:alpha-Glucosidases; D050111:Imino Sugars
D000606:Amino Sugars; D053138:Cyclohexenes; D005959:Glucosidases; D065089:Glycoside Hydrolase Inhibitors; D006595:Hexosamines; D007294:Inositol; D000520:alpha-Glucosidases; C042908:validamine; C030791:valienamine; C043270:valiolamine; D050111:Imino Sugars; C034251:4-nitrophenyl-alpha-glucosidase; C042059:glucosidase I