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Sucrase-isomaltase (SI) is a dual-function enzyme complex anchored to the brush border membrane of the small intestinal mucosa. It belongs to the glycosyl hydrolase family 31 and plays a pivotal role in the terminal digestion of dietary carbohydrates by hydrolyzing sucrose into glucose and fructose, and isomaltose into glucose (UniProt P14410). This enzyme is a primary therapeutic target for the management of type 2 diabetes mellitus; alpha-glucosidase inhibitors such as acarbose and miglitol competitively inhibit SI to delay carbohydrate absorption and mitigate postprandial hyperglycemia (StatPearls, 2023). Beyond metabolic disease, genetic mutations in the SI gene cause congenital sucrase-isomaltase deficiency (CSID), a condition leading to malabsorption, osmotic diarrhea, and failure to thrive in infants (NIH, 2022). For patients with CSID, sacrosidase (Sucraid) is used as an enzyme replacement therapy to restore sucrase activity (PubChem, 2024). Therapeutic modulation of this target is highly effective for glycemic control but is frequently associated with gastrointestinal side effects, such as flatulence and abdominal discomfort, caused by the colonic fermentation of unabsorbed sugars.
Competitive inhibition of the alpha-glucosidase enzymes in the intestinal brush border to delay carbohydrate digestion (StatPearls, 2023); or enzyme replacement therapy to restore sucrase activity in deficient patients (PubChem, 2024).
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