title: Involvement of iron (ferric) reduction in the iron absorption mechanism of a trivalent iron-protein complex (iron protein succinylate).
abstract: Iron protein succinylate is a non-toxic therapeutic iron compound. We set out to characterise the structure of this compound and investigate the importance of digestion and intestinal reduction in determining absorption of the compound. The structure of the compound was investigated by variable temperature Mössbauer spectroscopy, molecular size determinations and kinetics of iron release by chelators. Intestinal uptake was determined with radioactive compound force fed to mice. Reduction of the compound was determined by in vitro incubation with intestinal fragments. The compound was found to contain only ferric iron, present as small particles including sizes below 10 nm. The iron was released rapidly to chelators. Digestion with trypsin reduced the molecular size of the compound. Intestinal absorption of the compound was inhibited by a ferrous chelator (ferrozine), indicating that reduction to ferrous iron may be important for absorption. The native compound was a poor substrate for duodenal reduction activity, but digestion with pepsin, followed by pancreatin, released soluble iron complexes with an increased reduction rate. We conclude that iron protein succinylate is absorbed by a mechanism involving digestion to release soluble, available ferric species which may be reduced at the mucosal surface to provide ferrous iron for membrane transport into enterocytes.
authors.affiliation: Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK.
authors.forename: K B
authors.initials: KB
authors.lastname: Raja
authors.forename: S E
authors.initials: SE
authors.lastname: Jafri
authors.forename: D
authors.initials: D
authors.lastname: Dickson
authors.forename: A
authors.initials: A
authors.lastname: Acebròn
authors.forename: P
authors.initials: P
authors.lastname: Cremonesi
authors.forename: G
authors.initials: G
authors.lastname: Fossati
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
mesh_terms: D000818:Animals; D001682:Biological Availability; D005297:Ferrozine / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D008667:Metalloproteins / Q000493:pharmacokinetics*; D051379:Mice; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D015204:Spectroscopy, Mossbauer; D013386:Succinates / Q000493:pharmacokinetics*
chemical_list: D007502:Iron Chelating Agents; D008667:Metalloproteins; D013386:Succinates; D005297:Ferrozine; D010088:Oxidoreductases; C055066:iron protein succinylate