Orthophosphate affects iron(III) bioavailability via a mechanism involving stabilization and delivery of ferric hydroxide-phosphate nanoparticles
2021
Wu, Haohao | Guo, Tengjiao | Li, Shiyang | Zhao, Yuanhui | Zeng, Mingyong
Orthophosphate is endogenously present in gastrointestinal fluids and increasingly ingested as additives in processed foods. However, its effect and mechanism of action on iron bioavailability remains controversial and largely unknown. Here, at initial dissolved P/Fe ratios ((P/Fe)ᵢₙᵢₜ) ≥ 0.6, orthophosphate completely prevents hydrolytic Fe(III) precipitation at neutral pH by mediating the formation of negatively-charged (≈−29 mV ζ-potential) ferric hydroxide-phosphate nanoparticles (Fe(OH)P-NPs) consisting of ≈3.8-nm-diameter monomers. Fe(OH)P-NPs have decreased size and Fe/P ratio with increasing (P/Fe)ᵢₙᵢₜ. Acidic pH and balanced salts in intestinal fluid counteract orthophosphate-mediated Fe(III) solubilization by weakening colloidal stability of Fe(OH)P-NPs. Protein digests from egg white, whey, casein, and fish muscle aid Fe(III) solubilization in intestinal fluid by stabilizing Fe(OH)P-NPs with casein digest displaying the highest Fe(III)-solubilizing capacity, and in calcein-fluorescence-quenching assay, deliver nanoparticulate Fe(III) to polarized Caco-2 cells via divalent-metal-transporter-1-dependent or endocytic pathways. Overall, our study provides a new paradigm for understanding orthophosphate’s role in iron bioavailability.
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