Copper(II)‐catalyzed lipid peroxidation in liposomes and erythrocyte membranes

Cu ++ was uniquely capable of catalyzing the peroxidation of rat erythrocyte membrane lipid in the presence of 10 mM H 2 O 2 , whereas several other transition metal ions were without significant effect. In contrast, peroxidation of soybean phospholipid liposomes could be catalyzed with decreasing efficiency by Co ++ , Cu ++ , Pb ++ , or Cr +++ also in the presence of H 2 O 2 . The effect of imidazole on Cu ++ ‐catalyzed lipid peroxidation was stimulatory in liposomes and inhibitory in membrane preparations, whereas EDTA, histidine, citrate and alanine inhibited peroxidation in both systems. EDTA could stop the peroxidation after initiation, but catalase could not, indicating that Cu ++ alone was necessary for the propagation of the chain reaction. Competitive inhibition studies with various scavengers of hydroxyl radicals or singlet oxygen and the absence of significant reaction enhancement by D 2 O indicated that neither of these reactive oxygen species was a major mediator in the Cu ++ ‐H 2 O 2 oxidative system. A copper‐oxygen complex may be directly involved in the initiation of peroxidation. Normal erythrocyte membranes and phospholipid liposomes also differ in their sensitivities toward external oxidative stress. In the absence of H 2 O 2 , Cu ++ (0.2 mM) was capable of catalyzing lipid peroxidation in liposomes, aged erythrocyte membranes and membranes from vitamin‐E‐deficient rats; however, freshly prepared membranes from control rats and liposomes containing α‐tocopherol required H 2 O 2 greater than 2 mM for the catalytic effect of Cu ++ to be observed.