Initiation of Lipid Peroxidation in Rat Liver Mitochondria by Chelated Iron-Oxygen Complexes.

Abstract

The mechanism of initiation of lipid peroxidation in rat liver mitochondria in the resting state by iron chelates of adenine nucleotides has been investigated. ADP was required at three times the concentration of Fe²⁺ for formation of an active complex and at ten times the concentration of Fe²⁺ for maximal activity to induce lipid peroxidation. Iron chelates with ATP showed as high activity as those with ADP for initiation of peroxidation, but those with AMP showed low activity. ADP-Fe³⁺, prepared from ADP and Fe(NH₄)(SO₄)₂, did not induce mitochondrial lipid peroxidation, whereas ADP-Fe²⁺, prepared by incubation of ADP with FeSO₄, oxidized to form a Fe³⁺-type complex, as characterized by spectroscopic analysis, did induce lipid peroxidation. The oxidation of ADP-Fe²⁺ to an ADP-Fe³⁺-type complex with associated oxygen uptake suggested the formation of an ADP-Fe³⁺-oxygen complex capable of initiating lipid peroxidation. The molar ratio of Fe³⁺ formation to oxygen uptake was approximately 2.5 on incubation of Fe²⁺ with ADP. The process of ADP-Fe²⁺-induced lipid peroxidation did not involve superoxide, H₂O₂, or the OH-radical, because it was not inhibited by superoxide dismutase, catalase, or mannitol, an OH-radical scavenger.