Redox cycling of iron and lipid peroxidation

Abstract

Mechanisms of iron-catalyzed lipid peroxidation depend on the presence or absence of preformed lipid hydroperoxides (LOOH). Preformed LOOH are decomposed by Fe(II) to highly reactive lipid alkoxyl radicals, which in turn promote the formation of new LOOH. However, in the absence of LOOH, both Fe²⁺ and Fe³⁺ must be available to initiate lipid peroxidation, with optimum activity occurring as the Fe²⁺/Fe³⁺ ratio approaches unity. The simultaneous availability of Fe²⁺ and Fe³⁺ can be achieved by oxidizing some Fe²⁺ with hydrogen peroxide or with chelators that favor autoxidation of Fe²⁺ by molecular oxygen. Alternatively, one can use Fe³⁺ and reductants like superoxide, ascorbate or thiols. In either case excess Fe²⁺ oxidation or Fe³⁺ reduction will inhibit lipid peroxidation by converting all the iron to the Fe³⁺ or Fe²⁺ form, respectively. Superoxide dismutase and catalase can affect lipid peroxidation by affecting iron reduction/oxidation and the formation of a (1∶1) Fe²⁺/Fe³⁺ ratio. Hydroxyl radical scavengers can also increase or decrease lipid peroxidation by affecting the redox cycling of iron.