The role of iron-sulfur clusters in in vivo hydroxyl radical production.
The in vivo production of HO- requires iron ions, H2O2 and O2- or other oxidants but probably does not occur through the Haber-Weiss reaction. Instead oxidants, such as O2-, increase free iron by releasing Fe(II) from the iron-sulfur clusters of dehydratases and by interfering with the iron-sulfur clusters reassembly. Fe(II) then reduces H2O2, and in turn Fe(III) and the oxidized cluster are re-reduced by cellular reductants such as NADPH and glutathione. In this way, SOD cooperates with cellular reductants in keeping the iron-sulfur clusters intact and the rate of HO. production to a minimum. O2- and other oxidants can release iron from Fe(II)-containing enzymes as well as copper from thionein. The released Fe(III) and Cu(II) are then reduced to Fe(II) and Cu(I) and can then participate in the Fenton reaction. In mammalian cells oxidants are able to convert cytosolic aconitase into active IRE-BP, which increases the "free" iron concentration intracellularly both by decreasing the biosynthesis of ferritin and increasing biosynthesis of transferrin receptors. The biological role of the soxRS regulon of Escherichia coli, which is involved in the adaptation toward oxidative stress, is presumably to counteract the oxidative inactivation of the iron clusters and the subsequent release of iron with consequent increased rate of production of HO.
Liochev
S L
SL
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
D004926:Escherichia coli / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000633:toxicity
D007506:Iron-Sulfur Proteins; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; D013482:Superoxide Dismutase; D006836:Hydro-Lyases