| Abstract
| - Uptake of dietary iron is essential for replenishment of body stores. A role for the hormonegastrin in iron uptake as a chelator of ferric ions in the gastric lumen has been proposed previously [Baldwin,G. S. (1992) Med. Hypotheses 38, 70−74]. Here, spectroscopic evidence of selective, high-affinity bindingof ferric ions to progastrin-derived peptides in aqueous solution at low pH is provided. The maximum at281 nm in the absorption spectrum of glycine-extended gastrin17 at pH 4.0 increased (2.07 ± 0.30)-foldin the presence of ≥2 equiv of ferric ions. Titration of glycine-extended gastrin17 with ferric ions understoichiometric conditions indicated that the stoichiometry of binding was 2.00 ± 0.28 mol of Fe3+/mol ofpeptide. Fluorescence quenching experiments yielded values for the stoichiometry and apparent dissociationconstant of the ferric ion−glycine-extended gastrin17 complex at pH 4.0 of 2.39 ± 0.17 mol of Fe3+/moland 0.62 ± 0.19 μM, respectively. No interaction was detected with Co2+, Cu2+, Mn2+, or Cr3+. Electronparamagnetic resonance spectroscopy suggested that the iron ligands were either oxygen or sulfur atoms.Fluorescence quenching experiments with peptides derived from the glycine-extended gastrin17 sequenceindicated that one or more of the five glutamic acid residues were necessary for iron binding. The bindingof ferric ions by glycine-extended gastrin17 at low pH is consistent with a role for progastrin-derivedpeptides in iron uptake from the lumen of the gastrointestinal tract.
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