sodium ferrous citrate (SCF, Eisai / Ferromia / Nemiffero)

Structures of the human sodium-citrate cotransporter NaCT with and without substrates.

Sauer David B DB, Song Jinmei J, Marden Jennifer J JJ, Wang Bing B et al.

The human sodium-citrate cotransporter NaCT imports various tri- and dicarboxylates into the cell as TCA cycle intermediates. This substrate uptake process is driven by an inward sodium gradient. The protein is a member of the Divalent Anion-Sodium Symporter (DASS) family. Whereas extensive biochemical and structural studies have been carried out for NaCT, how the substrate binding and translocation is coupled to the sodium gradient remains unclear. Here using single particle cryo-electron microscopy, we determined the structures of the human NaCT protein in three states: sodium-free, in the presence of sodium, and sodium- and substrate-bound. These structures suggest a simultaneous binding mechanism for sodium-substrate coupling, distinct from the sequential binding, conformational selection mechanism previously observed for the bacterial DASS protein VcINDY.

CORR Insights®: Is a Resorbable Citrate-based Bioceramic Device Associated With Osseous Integration? An Early Retrospective MRI Analysis.

DeCoster Thomas A TA

Sodium-Containing Pharmaceutical Products as Contributors to Cardiovascular Risk.

White William B WB, Kovacs Richard J RJ

Restricting sodium intake has been identified as one of the most cost-effective measures to improve public health. The substantial improvements in blood pressure and cardiovascular outcomes observed after dietary sodium restriction in clinical trials and observational studies provide evidence-based support for national strategies that recommend limits on daily sodium consumption. Although dietary sources of sodium account for most of an individual's intake, the sodium content of pharmaceutical products can also contribute to excess sodium intake, thereby increasing cardiovascular risk. Sodium is included in oral medications as an active ingredient (or as a cation for an active ingredient) or to enhance solubility. The sodium content of certain medications can exceed the daily recommended maximal sodium intake if higher doses are administered. In this contemporary review, we describe the basis of cardiovascular risk with increased sodium intake as it pertains to the clinical relevance of medications with a high-sodium content that are associated with increases in blood pressure, development of hypertension, and adverse cardiovascular outcomes. Improvements in approaches to sodium content labeling and prescriber education are warranted to ensure that patients receive appropriate therapeutic options.

Redox implications of oxygen binding in hemoglobin and myoglobin: Thermodynamics of the (Fe3+/Fe2+) oxidation-reduction of heme-bound fluoride complexes versus fluoride binding.

Flanders Kayla K, Mathew Annie A, Lockwood Mary M, Frankenfield Ashley A et al.

In this study, the thermodynamics of the one-electron (Fe2+/Fe3+) oxidation-reduction of the heme-bound fluoride complexes of adult hemoglobin (Hb-F) and horse heart myoglobin (Mb-F) were addressed to interpret the molecular changes these proteins undergo during the redox reactions. We measured the enthalpy (ΔHo') and entropy (ΔSo') of these reactions at pH 5 and pH 7, and also for the oxidation-reduction reactions of the metaquo complexes and for fluoride binding. The temperature dependence of the reduction potentials (Em) of Hb-F and Mb-F showed two redox pathways with distinct thermodynamic properties in the 5 to 45 °C temperature range, but only at pH 5. The Em-T plots of Hb-F and Mb-F were complementary to each other, with opposing signs in their ΔHo' and ΔSo'. The redox reactions of the metaquo heme complexes and the heme-bound fluoride complexes (at pH 7) show no evidence of a bifurcated redox pathway. Given the similarities of the heme-ligand structures of oxy- and fluoride-bound complexes and comparable thermodynamics between oxidation and oxygen binding equilibrium, we theorize that one of the thermodynamic pathways is for stabilization of the heme-bound fluoride complex upon the redox change and the other is associated to a redox pathway that stabilizes the heme ferrous state, a route presumably associated to the unligated heme ferric-to-ferrous equilibrium. The serendipitous mixing of these redox pathways in the heme-bound fluoride complexes highlights the specificity of the heme proteins for oxygen binding and the possible use of these pathways for their respective physiological roles of storage and transport. The thermodynamics of the redox reactions of the heme-bound fluoride complexes of hemoglobin and myoglobin exhibit properties similar to those of their oxygen binding equilibria, which govern transport and oxygen storage.