Iron Uptake Is Enhanced in Caco-2 Cell Monolayers by Cysteine and Reduced Cysteinyl Glycine

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Abstract
Human and animal studies have shown that amino acids and peptides influence iron absorption from the intestinal lumen. This study was conducted using Caco-2 cell monolayers as the experimental model to determine whether similar effects on iron absorption occur. Conditions were chosen to mimic the pH of the intestinal lumen and the most likely order whereby ferric and ferrous forms of iron would combine with various amino acids and dipeptides resulting from protein digestion. We demonstrated the enhancing effect of cysteine and reduced cysteinyl glycine on iron uptake by Caco-2 cells. The addition of glutathione to the transport media had no effect on uptake from ferrous or ferric iron complexes, nor did it affect iron solubility. Cysteine and reduced cysteinyl glycine increased iron solubility when added to a solution containing insoluble iron. This effect is different from that of ascorbate, which must be combined with soluble ferric iron at pH 2 to reduce and solubilize iron. Taken together, these observations are evidence that cysteine and reduced N-terminal cysteine peptides are capable of enhancing iron uptake from soluble and insoluble ferric iron. These results qualitatively reflect those observed in human studies. Our results indicate that glutathione requires digestion to Cys or Cys-Gly in order to promote iron uptake. The similarity between this study and human studies further reinforces that the Caco-2 cell model is a useful tool in studies of iron absorption and bioavailability.