isomaltase

Isomaltase is a brush-border enzyme of the small intestine that catalyzes the hydrolysis of alpha-1,6-glycosidic bonds found in isomaltose and in α-limit dextrins, releasing glucose. It is one of the activities of the sucrase–isomaltase enzyme complex, which also contains sucrase activity that splits sucrose into glucose and fructose. In humans, the enzyme is expressed in the enterocytes of the small intestine, primarily in the proximal small intestine, and is anchored to the apical cell membrane as part of the membrane-bound enzyme complex.

Isomaltase is encoded by the SI gene. The encoded polypeptide is synthesized as a single precursor that is proteolytically processed to yield two catalytic domains corresponding to sucrase and isomaltase activities, which together confer the dual function of the complex. The enzyme acts on dietary starch breakdown products and is essential for complete digestion of starch-related dextrins.

Substrates include isomaltose and α-limit dextrins with α-1,6 linkages. The optimum pH is near neutral, compatible with the small-intestinal milieu. The enzyme can be inhibited by general alpha-glucosidase inhibitors and dietary factors that impact carbohydrate digestion.

Clinical relevance: Congenital sucrase–isomaltase deficiency (CSID) results from mutations in the SI gene and leads to impaired digestion of sucrose and starch, causing osmotic diarrhea, abdominal pain, and bloating after carbohydrate-containing meals. Management includes dietary modification to reduce intake of sucrose and starch and enzyme replacement therapy with sacrosidase preparations that provide sucrase–isomaltase activity.

Isomaltase activity can be studied in pancreatic or intestinal brush-border preparations, and altered activity can serve as a diagnostic clue in CSID.