Role Of Hfe In Iron Metabolism

The first indication that class I MHC molecules are involved in cellular iron metabolism were observations that beta 2-microglobulin knockout mice develop iron overload.1-19-1 Subsequently, HFE protein was observed to have sequence and structural homology with MHC class I proteins,[4] but lacks a functional peptide binding groove and interactions with T cells.[20] HFE lacks a peptide-binding groove analogous to classical class I MHC proteins because of the greater proximity of its a1 and a2 helices. Moreover, C282Y, the predominant HFE mutation associated with hemochromatosis, encodes a tyrosine for cysteine substitution that results in loss of the disulfide bond in the a3 domain.[21] Without this disulfide loop, the molecule cannot fold properly, does not associate with beta 2-microglobulin, and is not expressed on the cell surface.[21] Wild -type and H63D HFE proteins form stable complexes with the transferrin receptor (TfR), whereas the C282Y mutant protein does not associate with TfR[22] The TfR-binding site of HFE is located on the C-terminal area of the a1 domain helix and in an adjacent loop.[22] This region of HFE is distinct from the peptide-binding site of classical class I MHC proteins. HFE binds TfR at or near the site where diferric transferrin binds. Although HFE competes with transferrin for binding sites on TfR, it is unclear if this is the mechanism whereby HFE regulates iron metabolism. In cells expressing HFE, TfR levels are increased and ferritin levels are decreased.[23] In cultured cells, expression of HFE reduces the uptake of ferritin from transferrin, suggesting that HFE has a role in regulating transferrin-mediated iron uptake. There are other proteins known to have a role in regulating iron absorption and metabolism. The relationship of their interaction with HFE is less well understood or is unreported.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

Get My Free Ebook

Post a comment