Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A second indolizidine alkaloid, epimeric with castanospermine, has been isolated from seeds of the Australian tree Castanospermum australe. The structure was established as 6-epicastanospermine by proton and carbon-13 nuclear magnetic resonance spectroscopy and mass spectrometry. 6-Epicastanospermine was found to be a potent inhibitor of amyloglucosidase, (an exo-1,4-alpha-glucosidase), a weak inhibitor of beta-galactosidase, and not to inhibit beta-glucosidase and alpha-mannosidase. These results indicate that glycosidase inhibitory activity cannot be predicted by comparison of the structure and stereochemistry with the appropriate sugars, since 6-epicastanospermine is an analog of mannose and not of glucose. The inhibition of amyloglucosidase was found to be competitive and to be more effective at higher pH values. Castanospermine and 6-epicastanospermine differed in their effect upon the mung bean processing enzymes, glucosidase I and II, in that the former is a potent inhibitor whereas the latter is a very poor inhibitor. Subtle alterations in stereochemistry of these alkaloids can therefore produce significant changes in their biological activity.
 ...
PMID:6-Epicastanospermine, a novel indolizidine alkaloid that inhibits alpha-glucosidase. 309 43

Castanospermine, an inhibitor of alpha-glucosidase activity, was injected into rats to determine its effects in vivo. Daily injections of alkaloid, at levels of 0.5 mg/g of body weight, or higher, for 3 days decreased hepatic alpha-glucosidase to 40% of control values, whereas alpha-glucosidase in brain was reduced to 25% of control values and that in spleen and kidney was reduced to about 40%. In liver, both the neutral (pH 6.5) and the acidic (pH 4.5) alpha-glucosidase activities were inhibited, but the former was more susceptible. On the other hand, beta-N-acetylhexosaminidase activity was elevated in the livers of treated animals, whereas beta-galactosidase activity was unchanged and alpha-mannosidase activity was somewhat inhibited. Livers of treated animals were examined by light and electron microscopy and compared to control animals to determine whether changes in morphology had occurred. In treated animals fed normal rat chow, the hepatocytes were smaller in size and simplified in structure, whereas the high-glucose diet lessened these alterations. Furthermore, in those animals receiving castanospermine at 1.0 mg or higher per g of body weight for 3 days, there was a marked decrease in the amount of glycogen in the cytoplasm, while a large number of lysosomes were observed that were full of dense, granular material. That this dense material was indeed glycogen was shown by the fact that it disappeared when blocks of fixed tissue were pretreated with alpha-amylase. Glycogen levels in liver, as measured either colorimetrically or enzymatically, were somewhat depressed at the higher levels of castanospermine.
 ...
PMID:Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals. 388 59

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).
 ...
PMID:Castanospermine, a tetrahydroxylated alkaloid that inhibits beta-glucosidase and beta-glucocerebrosidase. 640 22