Studies on the Transferrins of Adult Serum, Cord Serum, and Cerebrospinal Fluid

Abstract

Recent population studies by starch gel electrophoresis have revealed an elaborate genetically determined polymorphism of human and primate transferrin, the iron-binding protein in serum. At the present time twelve different molecular species of human transferrin have been identified (1). Transferrins whose electrophoretic mobilities are faster than the common type C are labeled B, and slower moving variants are labeled D. With the exception of transferrin C, which is found in high frequency in all populations, particular variants are rare and appear to be restricted to particular populations. Thus transferrin B0-1 is found in Navajo Indians, B, in Caucasians, Dchi in Chinese, and D1 in Negroes. The gene frequency for each of these variants is approximately 0.05; the remaining seven variants have been reported only in isolated individuals.The glycoprotein nature of transferrin has been investigated by Schultze et al. (2), who found a 5 per cent carbohydrate fraction composed of hexose, hexosamine, sialic acid, and fucose. Schultze and Schwick (3) had earlier described a reduction in the electrophorefic mobility of transferrin after incubation with neuraminidase, a bacterial and viral enzyme which cleaves the glycosidic bond joining sialic acid to a protein molecule. A similar effect had been observed by Perlmarm, Tamm, and Horsfall (4) for urinary mucoprotein after incubation with influenza virus.A brief report (5) previously described the stepwise action of neuraminidase in removing the four sialic acid residues from the transferrin molecule. The present study is concerned with an extension of the neuraminidase effect from transferrin C to certain genetic variants of human and primate transferrin. In addition, the transferrins of cord blood and cerebrospinal fluid are shown to be related by the neuraminidase effect to adult serum transferrin. Amino acid analyses of three human transferrins and a primate transferrin are also given.

Transferrin Microheterogeneity in Fetal Blood

“…The changes in Tf microheterogeneity patterns in fetal blood may result from a deficiency in the multiglycosyltransferase. Parker and Bearn [10] described that the faint, slower moving Tf bands in the cord serum of premature infants clearly identified in starch gel electrophoresis disappeared from the serum of the infants approximately 12 weeks after birth. Van Pelt et al [19] also demonstrated that carbohydrate-deficient Tf values (CDT, ^2-sialo-Tfs) in the cord serum of infants decrease rapidly after birth.…”

“…Parker et al [10,11] first demonstrated by vertical starch gel electrophoresis that different patterns of multiple faint Tf bands, which were related to the number of sialic acids on a Tf molecule, were observed between umbilical cord serum and adult serum. Verrijt et al [12] indicated a shift in the pattern of fetal Tf heterogeneity towards hyposialylated Tf fractions (^2-sialo-Tf) relative to maternal serum Tf by isoelectric focusing, but without determination of the percentage distribution of the Tf subfractions.…”

Genetic and Biochemical Studies of Transferrins and Hemoglobins of Galago

“…Several workers report th at differences in sialic acid content do not account for complex transferrin phenotypes of mammals (Gordon and Louis [1963]; Parker and Bearn [1962]; Blumberg and Warren [1961]). These reports are not supported by our work.…”

Human granulocyte/pollen-binding protein. Recognition and identification as transferrin.

“…A number oftransferrin variants have been described which show characteristic peptide maps suggestive of differences in primary structure (5,14). At Moqbel, and J. MacKay, unpublished observations).…”