Castanospermine, a tetrahydroxylated alkaloid that inhibits beta-glucosidase and beta-glucocerebrosidase

• Published in: Archives of biochemistry and biophysics Vol. 221; no. 2; p. 593
• Main Authors: Saul, R, Chambers, J P, Molyneux, R J, Elbein, A D
• Format: Journal Article
• Language: English
• Published: United States 01-01-1983
• Subjects: Alkaloids - pharmacology; Animals; beta-Glucosidase - antagonists & inhibitors; Cattle; Chemical Phenomena; Chemistry; Glucosidases - antagonists & inhibitors; Glucosylceramidase - antagonists & inhibitors; Glycoside Hydrolases - antagonists & inhibitors; Indolizines; Plants
• ISSN: 0003-9861
• DOI: 10.1016/0003-9861(83)90181-9

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) was tested against a variety of commercially available glycosidases and found to be a potent inhibitor of almond emulsin beta-glucosidase, and also to inhibit fungal beta-xylosidase. This alkaloid was inactive on yeast alpha-glucosidase, alpha- or beta-galactosidase, alpha-mannosidase, beta-N-acetylhexosaminidase, beta-glucuronidase, alpha-L-fucosidase. Fifty-percent inhibition of beta-glucosidase required about 10 micrograms/ml of castanospermine. The amount of inhibition was uniform throughout the time course, and the inhibition with regard to substrate concentration (p-nitrophenyl-beta-D-glucopyranoside) appeared to be of the mixed type. Castanospermine was also a potent inhibitor of beta-glucocerebrosidase when assayed with fibroblast extracts using either a fluorimetric or a radioactive assay. Interestingly enough, castanospermine also inhibited the lysosomal alpha-glucosidase, and this inhibition required comparable levels of alkaloid to that required for inhibition of beta-glucocerebrosidase. However, a number of other lysosomal glycosidases were not sensitive to castanospermine (i.e., alpha- or beta-galactosidase, alpha- or beta-mannosidase, alpha- or beta-L-fucosidase, beta-N-acetylhexosaminidase, beta-glucuronidase).