▪ Abstract Ferritin, a major form of endogenous iron in food legumes such as soybeans, is a novel and natural alternative for iron supplementation strategies where effectiveness is limited by acceptability, cost, or undesirable side effects. A member of the nonheme iron group of dietary iron sources, ferritin is a complex with Fe3+ iron in a mineral (thousands of iron atoms inside a protein cage) protected from complexation. Ferritin illustrates the wide range of chemical and biological properties among nonheme iron sources. The wide range of nonheme iron receptors matched to the structure of the iron complexes that occurs in microorganisms may, by analogy, exist in humans. An understanding of the chemistry and biology of each type of dietary iron source (ferritin, heme, Fe2+ ion, etc.), and of the interactions dependent on food sources, genes, and gender, is required to design diets that will eradicate global iron deficiency in the twenty-first century.

Iron, ferritin, and nutrition

https://www.cup.lmu.de/ac/kluefers/homepage/L/biominerals/ferritin_2010a.pdf

The iron redox and hydrolysis chemistry of the ferritins.

https://www.cup.lmu.de/ac/kluefers/homepage/L/biominerals/ferritin_2010c.pdf

The multifaceted capacity of Dps proteins to combat bacterial stress conditions: Detoxification of iron and hydrogen peroxide and DNA binding

http://www.cs.uno.edu/~csumma/docs/Summa_et_al_JMB_2002.pdf

Computational de novo Design, and Characterization of an A2B2 Diiron Protein

Dehydrogenases with their superb enantio- selectivity can be employed advantageously to pre- pare enantiomerically pure alcohols, hydroxy acids, and amino acids. For economic syntheses, however, the co-substrate of dehydrogenases, the NAD(P)(H) cofactor, has to be regenerated. Whereas the problem of regenerating NADH from NAD can be consid- ered solved, the inverse problem of regenerating NAD from NADH still awaits a definitive and practical solution. A possible solution is the oxidation of NADH to NAD with concomitant reduction of oxygen catalyzed by NADH oxidase (E.C. 1.6.-.-) which can reduce O2 either to undesirable H2O2 or to innocuous H2O. We have found and cloned two novel genes from Borrelia burgdorferi and Lactobacillus sanfranciscensis with hitherto only machine-annotat- ed NADH oxidase function. We have overexpressed the corresponding proteins and could prove the annotated function to be correct. As demonstrated with a more sensitive assay than employed previously, the two novel NADH oxidases reduce O2 to H2O.

/pdf/cofactor-regeneration-of-nad-from-nadh-novel-water-forming-58ivp1li92.pdf

Cofactor Regeneration of NAD+ from NADH: Novel Water-Forming NADH Oxidases

Kinetic studies of iron deposition catalyzed by recombinant human liver heavy, and light ferritins and Azotobacter vinelandii bacterioferritin using O2 and H2O2 as oxidants

DNA molecular wires have been studied extensively because of the ease with which molecules of controlled length and composition can be synthesized. The same has not been true for proteins. Here, we have synthesized and studied a series of consensus tetratricopeptide repeat (CTPR) proteins, spanning 4 to 20 nm in length, in increments of 4 nm. For lengths in excess of 6 nm, their conductance exceeds that of the canonical molecular wire, oligo(phenylene-ethylenene), because of the more gradual decay of conductance with length in the protein. We show that, while the conductance decay fits an exponential (characteristic of quantum tunneling) and not a linear increase of resistance with length (characteristic of hopping transport), it is also accounted for by a square-law dependence on length (characteristic of weakly driven hopping). Measurements of the energy dependence of the decay length rule out the quantum tunneling case. A resonance in the carrier injection energy shows that allowed states in the protein align with the Fermi energy of the electrodes. Both the energy of these states and the long-range of hopping suggest that the reorganization induced by hole formation is greatly reduced inside the protein. We outline a model for calculating the molecular-electronic properties of proteins.

Electronic Transport in Molecular Wires of Precisely Controlled Length Built from Modular Proteins.

The reaction of Fe2+ with O2 in the presence of horse spleen ferritin (HoSF) results in deposition of FeOH3 into the hollow interior of HoSF. This reaction was examined at low Fe2+/HoSF ratios (5-100) under saturating air at pH 6.5-8.0 to determine if H2O2 is a product of the iron deposition reaction. Three methods specific for H2O2 detection were used to assess H2O2 formation: (1) a fluorometric method with emission at 590 nm, (2) an optical absorbance method based on the reaction H2O2 + 3I- + 2H+ = I3- + 2H2O monitored at 340 nm for I3- formation, and (3) a differential pulsed electrochemical method that measures O2 and H2O2 concentrations simultaneously. Detection limits of 0.25, 2.5, and 5.0 microM H2O2 were determined for the three methods, respectively. Under constant air-saturation conditions (20% O2) and for a 5-100 Fe2+/HoSF ratio, Fe2+ was oxidized and the resulting Fe3+ was deposited within HoSF but no H2O2 was detected as predicted by the reaction 2Fe2+ + O2 + 6H2O = 2Fe(OH)3 + H2O2 + 4H+. Two other sets of conditions were also examined: one with excess but nonsaturating O2 and another with limiting O2. No H2O2 was detected in either case. The absence of H2O2 formation under these same conditions was confirmed by microcoulometric measurements. Taken together, the results show that under low iron loading conditions (5-100 Fe2+/HoSF ratio), H2O2 is not produced during iron deposition into HoSF using O2 as an oxidant. This conclusion is inconsistent with previous, carefully conducted stoichiometric and kinetic measurements [Xu, B., and Chasteen, N. D. (1991) J. Biol. Chem. 266, 19965], predicting that H2O2 is a quantitative product of the iron deposition reaction with O2 as an oxidant, even though it was not directly detected. Possible explanations for these conflicting results are considered.

Stuart Lindsay

Papers

Kinetic studies of iron deposition catalyzed by recombinant human liver heavy, and light ferritins and Azotobacter vinelandii bacterioferritin using O2 and H2O2 as oxidants

Electronic Transport in Molecular Wires of Precisely Controlled Length Built from Modular Proteins.

Hydrogen Peroxide Formation During Iron Deposition in Horse Spleen Ferritin Using O2 as an Oxidant

Kinetic studies of iron deposition in horse spleen ferritin using O2 as oxidant