Effects of castanospermine on purified lysosomal alpha-1,4-glucosidase

The indolizidine alkaloid castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) inhibits hydrolysis of maltose, glycogen and isomaltose by purified lysosomal alpha-glucosidase yielding Ki values of 0.095, 0.10 and 0.30 mumol/l, respectively. Castanospermine exhibited high affinity for both the maltose and isomaltose sites. In distinct contrast, the alkaloid exhibited little or no affinity for the site catalyzing hydrolysis of glycogen as indicated by a noncompetitive mode of inhibition. Kinetic data presented in this report indicate castanospermine to be a very potent inhibitor of lysosomal alpha-glucosidase.