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Publication Abstract from PubMed

A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 muM affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 A and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.

Ferritin couples iron and fatty acid metabolism.,Bu W, Liu R, Cheung-Lau JC, Dmochowski IJ, Loll PJ, Eckenhoff RG FASEB J. 2012 Jun;26(6):2394-400. doi: 10.1096/fj.11-198853. Epub 2012 Feb 23. PMID:22362897^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.