title: Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase.
abstract: Inhibition of intestinal α-glucosidases and pancreatic α-amylases is an approach to controlling blood glucose and serum insulin levels in individuals with Type II diabetes. The two human intestinal glucosidases are maltase-glucoamylase and sucrase-isomaltase. Each incorporates two family 31 glycoside hydrolases responsible for the final step of starch hydrolysis. Here we compare the inhibition profiles of the individual N- and C-terminal catalytic subunits of both glucosidases by clinical glucosidase inhibitors, acarbose and miglitol, and newly discovered glucosidase inhibitors from an Ayurvedic remedy used for the treatment of Type II diabetes. We show that features of the compounds introduce selectivity towards the subunits. Together with structural data, the results enhance the understanding of the role of each catalytic subunit in starch digestion, helping to guide the development of new compounds with subunit specific antidiabetic activity. The results may also have relevance to other metabolic diseases such as obesity and cardiovascular disease.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Kyra
authors.initials: K
authors.lastname: Jones
authors.forename: Lyann
authors.initials: L
authors.lastname: Sim
authors.forename: Sankar
authors.initials: S
authors.lastname: Mohan
authors.forename: Jayakanthan
authors.initials: J
authors.lastname: Kumarasamy
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Avery
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
authors.forename: Roberto
authors.initials: R
authors.lastname: Quezada-Calvillo
authors.forename: Buford L
authors.initials: BL
authors.lastname: Nichols
authors.forename: B Mario
authors.initials: BM
authors.lastname: Pinto
authors.forename: David R
authors.initials: DR
authors.lastname: Rose
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D020909:Acarbose / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D009005:Monosaccharides / Q000737:chemistry; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology; D013213:Starch / Q000378:metabolism*; D013394:Sucrase-Isomaltase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013402:Sugar Alcohols / Q000737:chemistry / Q000494:pharmacology; D013431:Sulfates / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; C114502:Kotalanol; D009005:Monosaccharides; D018036:Selenium Compounds; D013402:Sugar Alcohols; D013431:Sulfates; C497875:blintol; C427963:salacinol; C045621:miglitol; D017485:1-Deoxynojirimycin; D013213:Starch; D013394:Sucrase-Isomaltase Complex; D000520:alpha-Glucosidases; D020909:Acarbose