Involvement of iron (ferric) reduction in the iron absorption mechanism ofa trivalent iron-protein complex (iron protein succinylate)

Iron protein succinylate is a non-toxic therapeutic iron compound. We set o ut to characterise the structure of this compound and investigate the impor tance of digestion and intestinal reduction in determining absorption of th e compound. The structure of the compound was investigated by variable temp erature Mossbauer spectroscopy, molecular size determinations and kinetics of iron release by chelators. Intestinal uptake was determined with radioac tive compound Force fed to mice. Reduction of the compound was determined b y 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 r educed the molecular size of the compound. Intestinal absorption of the com pound was inhibited by a ferrous chelator (ferrozine), indicating that redu ction to ferrous iron may be important for absorption. The native compound was a poor substrate for duodenal reduction activity, but digestion with pe psin, Followed by pancreatin, released soluble iron complexes with an incre ased reduction rate. We conclude that iron protein succinylate is absorbed by a mechanism involving digestion to release soluble, available ferric spe cies which may be reduced at the mucosal surface to provide ferrous iron fo r membrane transport into enterocytes.