Castanospermine: an apparent tight-binding inhibitor of hepatic lysosomal alpha-glucosidase.
Castanospermine is a potent inhibitor of rat hepatic lysosomal alpha-glucosidase in vitro. The alkaloid showed time-dependent inhibition with an IC50 of 5 X 10(-6) M without preincubation and 1 X 10(-7) M with 1 hr of preincubation. Inhibition appeared competitive without preincubation but noncompetitive after preincubation. The time-dependent inactivation of the enzyme followed pseudo-first-order kinetics with an inactivation constant of 1.2 X 10(3) M-1 sec-1. The apparent irreversibility of enzyme inhibition by castanospermine is postulated to be by tight-binding inhibition.
Ellmers
B R
BR
Rhinehart
B L
BL
Robinson
K M
KM
D000470:Alkaloids / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012639:Seeds / Q000032:analysis; D014197:Trees; D054836:Indolizidines
D000470:Alkaloids; D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; C037806:castanospermine; D054836:Indolizidines