IN-VIVO INHIBITION OF BETA-GLUCOSIDASE AND BETA-MANNOSIDASE ACTIVITY IN RATS BY 2-DEOXY-2-FLUORO-BETA-GLYCOSYL FLUORIDES AND RECOVERY OF ACTIVITY IN-VIVO AND IN-VITRO

2-Deoxy-2-fluoro-beta-glucosyl and -beta-mannosyl fluorides administer ed to rats in a single dose(10 mg/kg) inhibited beta-glucosidase and b eta-mannosidase activity respectively after 1 h in brain, spleen, live r and kidney tissues. This inhibition, presumably caused by accumulati on of 2-deoxy-2-fluoroglycosyl-enzyme intermediates, indicates that in tact 2-deoxy-2-fluoroglycosyl fluorides are distributed to these organ s and, in the case of brain, that they cross the blood/brain barrier. beta-Glucosidase activity recovered completely or partially in brain, spleen, liver and kidney by 20-48 h. beta-Mannosidase activity partial ly recovered in all tissues by 48 h. beta-Galactosidase activity in br ain and kidney was not significantly affected by administration of eit her the gluco or manno compounds at this dosage, indicating that these inhibitors are directed towards specific glycosidases. Observation of similar relatively rapid rates of beta-glycosidase re-activation in v ivo and in tissue homogenates in vitro at 37 degrees C suggests that h ydrolysis or transglycosylation of 2-deoxy-2-fluoroglycosyl-enzymes, n ot protein synthesis, are the primary mechanisms involved in the recov ery of glycosidase activity inhibited by this class of compounds in vi vo.