Studies of the Metabolism of Asialotransferrins: Relationship Between the Carbohydrate Composition of Bovine, Canine, and Porcine Asialotransferrins and their Metabolic Behavior in the Rabbit

Abstract

The catabolism and distribution of bovine, canine, and porcine asialotransferrins relative to the corresponding parent proteins were studied in rabbits using a dual-isotope tracer technique. The capillary transfer rates and the partitions between intra- and extravascular spaces of these asialotransferrins did not differ significantly from the corresponding values for the control proteins but the asialotransferrins were catabolized faster. However, the difference in catabolic rates only amounted to 13–20%, which was in the same order as established previously for rabbit asialotransferrin (15%) but was considerably less than for human asialotransferrin (350%). This behavior clearly indicates that, in contradistinction to human asialotransferrin, bovine, canine, and porcine asialotransferrins are not eliminated from the plasma of rabbits via the Ashwell–Morell pathway for asialoglycoproteins.To explain the discrepancy in the behavior in vivo of the heterologous asialotransferrins, the carbohydrate compositions of the native proteins were measured and compared. The data show that bovine, porcine, dog, and rabbit transferrins contain approximately half the amount of carbohydrate found for the human protein. Furthermore, the human asialotransferrin carbohydrate chains terminate with galactosyl residues, which can be cleaved by β-galactosidase, whereas bovine, porcine, dog, and rabbit asialotransferrins do not liberate galactose in the presence of β-galactosidase.These observations are consistent with the hypothesis that the rapid elimination of a heterologous asialotransferrin can only be expected if the terminal galactose residues are accessible and that the slightly accelerated catabolism of homologous and certain heterologous asialotransferrins is due to loss of negative charge from the protein.