Studies of the Metabolism of Asialotransferrins: The Mechanism for the Hypercatabolism of Human Asialotransferrin in the Rabbit

The behavior in vivo of human asialotransferrin in rabbits was studied in such a manner as to permit a comparison of this catabolic process with the generalized hepatic clearance mechanism for asialoglycoproteins described by Ashwell and Morell.Progressive desialylation of human transferrin in the range 50–100% yielded transferrin molecules with circulation times inversely proportional to the loss of sialic acid. The shape of plasma protein-bound radioactivity curves indicated that treatment of transferrin with neuraminidase resulted in at least two types of asialo derivatives. The biological half-life of one of them was close to 60% of that of control transferrin and the other one disappeared from the plasma with a half-life of approximately 1.5–2.5 h. Oxidation of over 50% of the terminal galactosyl groups in human asialotransferrin prolonged the circulation time of asialotransferrin.Assays of tissue radioactivities following mixed injection of human control and asialotransferrins showed that the two proteins possessed the same affinity for lung, kidney, and spleen, but asialotransferrin was preferentially taken up by the liver.On the basis of these observations, it seems likely that the mechanism which has been claimed as a generalized pathway for the clearance of asialoglycoproteins is also responsible for the rapid elimination of heterologous human asialotransferrin in the rabbit.