Desialylation of transferrin

Marz, L., Hatton, M. W., Berry, L. R. and Regoeczi, E, 1982, The structural heterogeneity of the carbohydrate moiety of desialylated human transferrin. Canadian Journal of Biochemistry 60, 624-630. 

Regoeczi et al. (1974) were able to find a 15% and a 29% increase in the rate of removal of homologous asialotransferrin preparations from the plasma of rabbits and humans, respectively. However, they observed that when human asialotransferrin was injected into rabbits, it was removed 3.5 times more rapidly than the homologous asialotransferrin. Removal of normal human transferrin from rabbit plasma was not significantly different from the normal rabbit compound. In subsequent work (Regoeczi and Hatton, 1974) was found that progressively desialylated human transferrin molecules had plasma half-lives inversely proportional to the loss of sialic acid. 

Fig. 4.5.4 Identification of mutations in the transferrin protein by neuraminidase treatment. Unusual patterns in the IEF of serum transferrin might lead to pitfalls in CDG diagnostics. These varying patterns are often due to mutations of charged amino acids in the protein backbone of the transferrin molecule, which might lead, for example, to an accumulation of trisialo transferrin bands (lane 3, indicated by a question mark). Further investigations are carried out by cleaving off charged sialic acid monosaccharide moieties from transferrin-linked oligosaccharides by neuraminidase treatment, followed by IEF and transferrin antibody staining. In the case of protein mutations, additional bands below (lane 4) or above (not shown) the desialylated transferrin form appear...

Over 95% of plasma iron is in the Fe + state bound to the glycoprotein transferrin, a monomeric /I i-globulin (M.W. 80,000). Electrophoretic studies have revealed the existence of 21 genetic variants. In some, single-amino-acid substitutions account for variation in electrophoretic mobility. Transferrin is synthesized primarily in the liver and appears at the end of the first month of fetal development. Its half-life in humans is about 8 days. Desialylation may be a requirement for its removal from plasma by the liver, as it is for other plasma proteins (Chapter 10). In fact, asialotransferrin is more rapidly cleared from plasma than transferrin. It is not required for intestinal absorption of iron. 

The carbohydrate moiety in transferrin is apparently not essential for iron binding or for interaction with the transferrin-receptor. Of interest, however, is the observation that partially desialylated transferrin appears in alcoholic subjects [17b], but whether this affects iron metabolism is uncertain [cf. 7]. 

Transferrins.—A study of the metabolism of desialylized transferrins has shown that bovine, canine, and porcine asialotransferrins are not cleared from rabbit plasma via the Ashwell-Morell pathway (c/. human asialotransferrin). The glycopeptides of human transferrin are heterogeneous, so that the removal of... 

Removal of the penultimate sugar, mostly galactose, leads to a normalization of both the survival time in the circulation and the distribution among organs. On the first sight the extraordinary behaviour of asialo-transferrin did not fit in this general scheme, because desialylation apparently did not reduce the half-life. More detailed studies finally revealed that small amounts of asialo-transferrin are... 

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