Jump to main content
Jump to site search


Ferritin exhibits Michaelis–Menten behavior with oxygen but not with iron during iron oxidation and core mineralization

Author affiliations

Abstract

The excessively high and inconsistent literature values for Km,Fe and Km,O2 prompted us to examine the iron oxidation kinetics in ferritin, the major iron storage protein in mammals, and to determine whether a traditional Michaelis–Menten enzymatic behavior is obeyed. The kinetics of Fe(II) oxidation and mineralization catalyzed by three different types of ferritins (recombinant human homopolymer 24H, HuHF, human heteropolymer ∼21H:3L, HL, and horse spleen heteropolymer ∼3.3H:20.7L, HosF) were therefore studied under physiologically relevant O2 concentrations, but also in the presence of excess Fe(II) and O2 concentrations. The observed iron oxidation kinetics exhibited two distinct phases (phase I and phase II), neither of which obeyed Michaelis–Menten kinetics. While phase I was very rapid and corresponded to the oxidation of approximately 2 Fe(II) ions per H-subunit, phase II was much slower and varied linearly with the concentration of iron(II) cations in solution, independent of the size of the iron core. Under low oxygen concentration close to physiological, the iron uptake kinetics revealed a Michaelis–Menten behavior with Km,O2 values in the low μM range (i.e. ∼1–2 μM range). Our experimental Km,O2 values are significantly lower than typical cellular oxygen concentration, indicating that iron oxidation and mineralization in ferritin should not be affected by the oxygenation level of cells, and should proceed even under hypoxic events. A kinetic model is proposed in which the inhibition of the protein's activity is caused by bound iron(III) cations at the ferroxidase center, with the rate limiting step corresponding to an exchange or a displacement reaction between incoming Fe(II) cations and bound Fe(III) cations.

Graphical abstract: Ferritin exhibits Michaelis–Menten behavior with oxygen but not with iron during iron oxidation and core mineralization

Back to tab navigation

Publication details

The article was received on 02 Jan 2019, accepted on 29 Jan 2019 and first published on 29 Jan 2019


Article type: Paper
DOI: 10.1039/C9MT00001A
Citation: Metallomics, 2019, Advance Article

  •   Request permissions

    Ferritin exhibits Michaelis–Menten behavior with oxygen but not with iron during iron oxidation and core mineralization

    F. Bou-Abdallah, N. Flint, T. Wilkinson, S. Salim, A. K. Srivastava, M. Poli, P. Arosio and A. Melman, Metallomics, 2019, Advance Article , DOI: 10.1039/C9MT00001A

Search articles by author

Spotlight

Advertisements