Alpha-glucosidase enzyme (GAA)

Alpha-glucosidase enzymes are a class of glycoside hydrolases that catalyze the hydrolysis of terminal, non-reducing α-1,4-linked glucose residues from oligosaccharides and disaccharides, releasing free α-glucose. The enzyme is essential for the final steps of carbohydrate digestion in the small intestine and for glycogen degradation in lysosomes. In humans, the best-known isoform is acid alpha-glucosidase (GAA), which is necessary for lysosomal glycogen breakdown. Deficiency in human GAA activity leads to Pompe disease, a severe metabolic myopathy due to lysosomal glycogen accumulation. As a therapeutic target, alpha-glucosidase is inhibited by drugs such as acarbose, miglitol, and voglibose, which are used to modulate postprandial hyperglycemia in type 2 diabetes. The enzyme is widely distributed in nature, with distinct forms in various tissues and across species. Its inhibitors are well-characterized and represent a validated pharmacological strategy to control carbohydrate absorption and blood glucose levels after meals.

Other names

Acid alpha-glucosidaseLysosomal alpha-glucosidaseMaltaseGAA (for gene/protein)α-D-glucoside glucohydrolase (systematic name)Glucosidase alpha, acid

Competitive enzyme inhibition (e.g., acarbose, miglitol, and voglibose inhibit substrate binding to decrease glucose release from dietary carbohydrates). Slowing of oligosaccharide-to-glucose conversion delays glucose absorption and blunts postprandial blood sugar rise.