Reduced hepatic iron uptake from rat aglycotransferrin.

Rat aglycotransferrin (rAgTf) was produced from the disialosyl diantennary fraction of rat transferrin (rTf) by treatment with peptide: N-glycosidase F. Following removal of the enzyme by gel filtration and isolation of the deglycosylated protein by lectin chromatography, rAgTf was compared to rTf both in vitro and in vivo. No significant differences were found between the two proteins with respect to affinity for iron and kinetics of Fe release from the N-lobe and C-lobe. The fluorescence emission spectrum of apo-rTf was red-shifted by approximately 3 nm relative to diferric rTf; however, no spectral difference was detected between rTf and rAgTf when the analogous forms (apo or diferric) were compared. Plasma clearance of radioactive iron administered to rats as either rTf or rAgTf was comparable. Reticulocytes took up iron from rAgTf slightly faster than from rTf. In contrast, Fe acquisition by the liver from rAgTf was significantly reduced relative to rTf. This finding contrasts sharply with earlier observations with asialotransferrin (rAsTf) and provides a basis for discounting charge loss as the mechanism of enhanced hepatic Fe uptake from rAsTf. It is suggested that the glycan complement of rTf, while unimportant for interaction of the protein with specific receptors, probably plays a role in the interaction with low-affinity hepatic binding sites.