Functional heterogeneity and pH-dependent dissociation properties of human transferrin

• Published in: Biochimica et biophysica acta Vol. 428; no. 3; pp. 766 - 771
• Main Authors: Princiotto, Joseph V., Zapolski, Edward J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.05.1976
• Subjects: Animals; Binding Sites; Humans; Hydrogen-Ion Concentration; Iron - blood; Kinetics; Macromolecular Substances; Protein Binding; Rabbits; Reticulocytes - metabolism; Transferrin - metabolism; HEPES
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(76)90207-5

Human diferric transferrin was partially labeled with 59Fe at low or neutral pH (chemically labeled) and by replacement of diferric iron previously donated to rabbit reticulocytes (biologically labeled). Reticulocyte 59 uptake experiments with chemically labeled preparations indicated that iron bound at near neutral ph was more readily incorporated by reticulocytes than iron bound at low pH. The pH-dependent iron dissociation studies of biologically labeled transferrin solutions indicated that Fe 3+, bound at the site from which the metal was initially utilized by the cells, dissociated between pH 5.8 and 7.4. In contrast, lower pH (5.2–5.8) was required to effect dissociation of iron that had remained bound to the protein after incubation with reticulocytes. These findings suggest that each human transferrin iron-binding site has different acid-base iron-binding properties which could be related to the observed heterogenic rabbit reticulocyte iron-binding properties of human transferrin and identifies that the near neutral iron-donating site initially surrenders its iron to these cells.