title: Pathways in the binding and uptake of ferritin by hepatocytes.
abstract: The binding and uptake of rat liver ferritin by primary cultures of rat liver hepatocytes was studied in order to assess the relative importance of saturable, high-affinity pathways and nonspecific processes in the incorporation of the protein by the cells. To minimize artifacts, ferritin not subjected to heat treatment and labeled in vivo with 59Fe was used. Binding to cell membranes was estimated from incubations performed at 4 degrees C. After 2 h, when a steady state in cell-associated ferritin had been achieved, approx. 4-10(4) binding sites per cell were observed, with an affinity constant for ferritin of 1 x 10(9) M-1. At 37 degrees C, the maximal uptake from these sites was 1.3 x 10(5) ferritin molecules/cell per h. For ferritin molecules bearing an average of 2400 iron atoms, this uptake amounts to 5 x 10(6) iron atoms/cell per min. Half-maximal uptake was achieved at a ferritin concentration, or KM1, of 3 x 10(-9) M. Although uptake rates at least a thousand times greater could be achieved by binding to the much larger number of low-affinity sites, the apparent KM2 for such 'nonspecific' uptake was 4 x 10(-7) M. At ferritin concentrations up to 2 nM, at least 90% of ferritin bound and taken up by hepatocytes involves saturable, high-affinity sites, presumably true ferritin receptors.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: K
authors.initials: K
authors.lastname: Osterloh
authors.forename: P
authors.initials: P
authors.lastname: Aisen
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005293:Ferritins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D033862:Iron-Binding Proteins; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D007504:Iron Radioisotopes; D033862:Iron-Binding Proteins; D011956:Receptors, Cell Surface; C027293:ferritin receptor; D005293:Ferritins