Related Experiment Video
Updated: Jan 26, 2026

A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
Published on: April 11, 2014
Transferrin Cycle and Clinical Roles of Citrate and Ascorbate in Improved Iron Metabolism
1School of Chemistry , The University of Sydney , Sydney , NSW 2006 , Australia.
Abstract:
Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle was studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency, and neurodegeneration. Biolayer interferometry (BLI) enabled direct kinetic and thermodynamic measurements for all Tf-cycle steps in a single in vitro experiment using Tf within blood serum or released into the medium by cultured liver cells. In these media, known Tf cycle features were reproduced, and unprecedented insights were gained into conditions of rapid endosomal (pH 5.6) Fe(III) release from the Tf-Tf receptor 1 (TfR1) adduct. This release occurred via synergistic citrate and ascorbate effects, which pointed to respective roles as the likely elusive Fe chelator and reductant within the Tf cycle. These results explain enhanced cellular Fe uptake by ascorbate, the clinical efficacy of anemia treatment with Fe citrate and ascorbate, and dietary effects associated with loss of Fe homeostasis, including the large health burden of infections and neurodegeneration.
Related Concept Videos
The Early Endosome: Endocytosis of Transferrin
The Citric Acid Cycle
What is Metabolism?
What are Biogeochemical Cycles?
The Water Cycle
The Phosphorus Cycle

