Iron metabolism in aerobes: Managing ferric iron hydrolysis and ferrous iron autoxidation

Aerobes and anaerobes alike express a plethora of essential iron enzymes; in the resting state, the iron atom(s) in these proteins are in the ferrous state. For aerobes, ferric iron is the predominant environmental valence form which, given ferric iron's aqueous chemistry, occurs as ‘rust’, insoluble, bio-inert polymeric ferric oxide that results from the hydrolysis of [Fe(H2O)6]3+. Mobilizing this iron requires bio-ferrireduction which in turn requires managing the rapid autoxidation of the resulting FeII which occurs at pH > 6. This review examines the aqueous redox chemistry of iron and the mechanisms evolved in aerobes to suppress the ‘rusting out’ of FeIII and the ROS-generating autoxidation of FeII so as to make this metal ion available as the most ubiquitous prosthetic group in metallobiology.

► Iron is a ubiquitous redox cofactor.
► Iron's aerobic aqueous redox chemistry strongly limits its bioavailability and redox stability.
► Aerobic iron metabolism involves cycles of ferrireduction and ferroxidation.
► The electrode potential of the ferrous-ferric couple is ‘tuned’ for this bio-metabolism by specific coordination.