The mucosal redox gateway for dietary iron absorption: integrating gastrointestinal mucus, Fe(II)/Fe(III) speciation and ligand-centred valence tautomerism.

Non-haem dietary iron reaches the duodenum as a dynamic mixture of Fe(III) and Fe(II) complexes whose solubility and exchange kinetics are strongly influenced by pH, reductants, proteases, lipases, carbohydrases, and competing ligands. Canonical models place ferrireduction by duodenal cytochrome b and Fe(II) transport by divalent metal transporter 1 at the centre of absorption, but usually treat gastrointestinal mucus as a passive diffusion barrier. Evidence that mucins bind iron and other metal cations suggests a more active role. This review integrates established epithelial transport biology with mucin coordination chemistry and proposes a mucosal redox gateway: gastric and duodenal mucus transiently captures iron, suppresses premature hydrolysis and precipitation, and presents an exchangeable iron pool to the apical surface. Within this pool, Fe(III)/Fe(II) interconversion could be coupled to reversible oxidation-state changes in mucin-associated or low-molecular-mass ligands. We use the term ligand-centred valence tautomerism narrowly for an intracomplex redox equilibrium and distinguish this testable chemical hypothesis from the established phenomenon in discrete coordination compounds. The model predicts spatial gradients in iron speciation across mucus, redox- and pH-dependent exchange with mucin, and altered epithelial flux after selective modification of mucin functional groups. It provides a framework for explaining why ascorbate, gastric acidity, inflammation, mucus composition and competing metals influence iron bioavailability. Direct validation will require operando X-ray absorption spectroscopy, Mössbauer or electron paramagnetic resonance measurements, redox-resolved mass spectrometry and isotope-tracer transport in human mucus-organoid systems.