Altered glycosidase activity in the liver of rats with galactosamine-induced alpha 1-antiprotease deficiency.
Previous studies have shown that chronic administration of D-galactosamine (GalNH2) in rats produces alpha 1-antiprotease (AAP) deficiency and causes accumulation of aberrantly glycosylated AAP in hepatic granules. In order to examine the disordered mechanism which produces this altered glycosylation, the activities of 6 glycosidases in liver homogenates of control and AAP-deficient rats were determined. GalNH2 treatment increases acid pH glycosidase activity, while it decreases intermediate pH alpha-mannosidase and alpha-glucosidase activities. beta-D-Glucosidase, beta-D-mannosidase and beta-D-N-acetylglucosaminidase activities, measured at acid pH, increase more than 2-fold in the GalNH2-treated rats compared to controls. alpha-D-Glucosidase activity measured at intermediate pH decreases 2.5-fold in the experimental rats. alpha-L-Fucosidase and acid phosphatase activities are not significantly changed by GalNH2 treatment. alpha-D-Mannosidase activity can be separated into 2 fractions by ion exchange chromatography. Acid pH alpha-D-mannosidase is increased nearly 2-fold in the GalNH2-treated rats. Intermediate pH alpha-D-mannosidase optimum is decreased alpha-D-mannosidase activities have been observed in humans with AAP deficiency. alpha-Glucosidases and alpha-mannosidases play a crucial role in glycoprotein synthesis. The altered synthesis and structure of AAP in GalNH2-induced AAP deficiency may be a reflection of altered enzyme activities.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002852:Chromatography, Ion Exchange; D005688:Galactosamine / Q000008:administration & dosage / Q000633:toxicity*; D005959:Glucosidases / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008361:Mannosidases / Q000032:analysis / Q000378:metabolism; D011480:Protease Inhibitors / Q000172:deficiency*; D051381:Rats; D005644:alpha-L-Fucosidase / Q000378:metabolism
D011480:Protease Inhibitors; D005688:Galactosamine; D000135:Acid Phosphatase; D005959:Glucosidases; D006026:Glycoside Hydrolases; D008361:Mannosidases; D005644:alpha-L-Fucosidase; D000118:Acetylglucosaminidase