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Conduritol B epoxide (CBE) is a derivative of the naturally occurring conduritol B and is a catalytic, site-directed, covalent inhibitor of acid beta-glucosidase1 and of alpha-glucosidase.2 Conduritol B epoxide binds covalently and irreversibly to the catalytic site of acid beta-glucosidase, which is the enzyme responsible for the conversion of glucosylceramide to ceramide.3 Gaucher disease, the most prevalent lysosomal storage disease, is caused by mutations in the gene encoding acid betaglucosidase resulting in a defect in the enzyme beta-glucosidase activity and a subsequent accumulation of glucosylceramide. Conduritol B epoxide can be used to rapidly reproduce the effects of Gaucher disease making it ideal for studies of this condition.4 Treatment with CBE results in glucocerebrosides accumulating in neurons, causing changes in axonal morphology, although CBE has no effect on dendrite development. Co-incubation with CBE and inhibitors of sphingolipid synthesis such as fumonisin B1, an inhibitor of acylation of sphingoid long-chain bases, antagonizes the effects of CBE.5
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