Hepatic uptake and degradation of trace doses of asialofetuin and asialoorosomucoid in the intact rat

Asialoorosomucoid and asialofetuin were prepared by using sialidase, which was removed chromatographically before the proteins were labelled with radioactive iodine. After intravenous administration of a small amount oa asialoglycoprotein (3--4 microgram/100 g body wt.) protein-bound and non-protein radioactivities in plasmas and livers of rats were determined at intervals over a period of 30 min. Transfer of either tracer protein from plasma to liver was almost complete in 5 min. Proteolysis of asialofetuin was evident very shortly thereafter, but degradation of asialoorosomucoid commenced after a significant delay and was initially slow relative to that of asialofetuin. Studies in vitro with crude hepatic lysosomal enzyme preparations indicated that asialoorosomucoid was less readily digested than asialofetuin, and that desialylation of orosomucoid or fetuin did not noticeably increase the susceptibility of these proteins to protease action. Proteolysis of asialofetuin was also demonstrable in liver homogenates in conditions under which albumin and asialotransferrin were stable. A generalized mathematical model was devised to represent the uptake and degradation of asialoglycoproteins by the liver. The theoretical assumptions that gave the best fits with experiment are outlined and discussed.