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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #285269
Title: Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase

Author
item JONES, KYRA - University Of Waterloo
item SIM, LYANN - Children'S Nutrition Research Center (CNRC)
item MOHAN, SANKAR - Simon Fraser University
item KUMARASAMY, JAYAKANTHAN - Simon Fraser University
item LIU, HUI - Simon Fraser University
item AVERY, STEPHEN - Children'S Nutrition Research Center (CNRC)
item NAIM, HASSAN - Hannover School Of Veterinary Medicine
item QUEZADA-CALVILLO, ROBERTO - Arkansas Children'S Nutrition Research Center (ACNC)
item NICHOLS, BUFORD - Children'S Nutrition Research Center (CNRC)
item PINTO, B. MARIO - Simon Fraser University
item ROSE, DAVID - University Of Waterloo

Submitted to: Bioorganic and Medicinal Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2011
Publication Date: 5/24/2011
Citation: Jones, K., Sim, L., Mohan, S., Kumarasamy, J., Liu, H., Avery, S., Naim, H.Y., Quezada-Calvillo, R., Nichols, B.L., Pinto, B., Rose, D.R. 2011. Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase. Bioorganic and Medicinal Chemistry. 19(13):3929-3934.

Interpretive Summary: Food starches provide most food glucose in the form of large insoluble granules. Inhibition of starch digestion is a dietary approach to controlling blood glucose and serum insulin levels in individuals with insulin-resistant (Type II) diabetes. The two human intestinal enzyme complexes are maltase-glucoamylase and sucrase-isomaltase. Each gene product incorporates two enzymes responsible for the final step of starch digestion to absorbable free glucose. Here we compared the inhibitions of the four individual enzyme subunits of both complexes by clinical inhibitors, acarbose and miglitol, and some newly discovered inhibitors from an Ayurvedic remedy used in Asia for the treatment of Type II diabetes. We showed that the inhibitory compounds introduce selectivity towards the four enzyme subunits. Together with our published 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.

Technical Abstract: Inhibition of intestinal alpha-glucosidases and pancreatic alpha-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.