use of active sitedirected inhibitors to study in situ degradation of glycoproteins by the perfused rat liver use was made of the asialoglycoprotein receptor system in a perfused rat liver in order to study lysosomal degradation and subsequent metabolism of radioactive derivatives of asialoovine submaxillary mucin and asialoalpha 1acid glycoprotein a trace of nacetyld63hgalactosaminelabeled asialoovine submaxillary 4 micrograms was completely taken up by the tissue in less than 20 min after 3 h 24 of the radioactivity from the mucin reappeared on newly synthesized serum glycoproteins that were secreted into the perfusate 63h galactose asialoalpha 1acid glycoprotein was also rapidly cleared by the liver however after 3 h greater than 60 of the radioactivity derived from this sugar labeled glycoprotein was secreted back into the perfusate as 3hglucose rat livers perfused with 015 mm betadgalactopyranosylmethylpnitrophenyltriazene lost 90 of their betadgalactosidase activity within 1 h while other representative glycosidases showed no change as followed by hydrolysis of pnitrophenylglycosides livers pretreated with this triazene compound metabolized 3hgalnac asialoovine submaxillary mucin normally but were unable to process 3hgal asialoalpha 1acid glycoprotein as evidenced by a complete inhibition of 3hglucose release following addition of the latter substrate metabolism of nacetyl14cglucosamine asialoalpha 1acid glycoprotein was similarly inhibited by 70 125ilabeled asialoalpha 1acid glycoprotein catabolism was not affected by the chemically induced betadgalactosidase deficiency subcellular fractionation of inhibitortreated livers accumulating radioactive carbohydrate showed the majority of the label was associated with a fraction enriched in lysosomes analysis of the trapped radioactivity by high resolution biogel p4 chromatography revealed nearly intact oligosaccharides minus only the reducing nacetylglucosamine of the chitobiose core direct comparison of these sugar chains with those isolated from human and canine gm1 gangliosidosis liver by silicic acid thin layer chromatography showed those isolated from rat liver to be identical to the major subset of oligosaccharides found in the human disease in similar experiments in which the galactosyl triazene was replaced by swainsonine an alphadmannosidase inhibitor catabolism of 14cglcnac asialoalpha 1acid glycoprotein resulted in the accumulation of a single oligosaccharide of the structure man314cglcnac1 these results demonstrate an endonacetylbetadglucosaminidase is active in rat liver lysosomes