Fenton-catalyzed lipid oxidation

Ceruloplasmin (Cp), secreted into the blood stream, appears to be ubiquitous in vertebrates. There is extensive in vitro evidence that Cp efficiently catalyzes the oxidation of Fe to Fe under near physiological conditions. The role of Cp in iron metabolism is widely accepted and there is strong evidence for a secondary role in copper transport/regulation. Defects in hepatic biosynthesis of Cp may result in diseases such as Wilson s disease. There is conclusive evidence that Cp is the source for the copper found in cytochrome c oxidase and CuZn-SOD in cells. Cp inhibition of Fenton chemistry-induced oxidative damage of deoxyribose, lipids, and DNA points to an antioxidant role, which would explain the increase in Cp concentration in response to acute infection or inflammation. 

Of course, in addition to HOCl there are many more ROS that are generated under inflammatory conditions, leading to different lipid oxidation products [137]. Here, attention will be focused on hydroxyl radicals (HO ) that are generated under in vivo conditions by the transition-metal catalyzed decomposition of H2O2, via the famous Fenton reaction [145], The HO react in diffusion-controlled fashion with basically all biomolecules and, thus, also with lipids [6],... 

Thus, superoxide itself is obviously too inert to be a direct initiator of lipid peroxidation. However, it may be converted into some reactive species in superoxide-dependent oxidative processes. It has been suggested that superoxide can initiate lipid peroxidation by reducing ferric into ferrous iron, which is able to catalyze the formation of free hydroxyl radicals via the Fenton reaction. The possibility of hydroxyl-initiated lipid peroxidation was considered in earlier studies. For example, Lai and Piette [8] identified hydroxyl radicals in NADPH-dependent microsomal lipid peroxidation by EPR spectroscopy using the spin-trapping agents DMPO and phenyl-tcrt-butylnitrone. They proposed that hydroxyl radicals are generated by the Fenton reaction between ferrous ions and hydrogen peroxide formed by the dismutation of superoxide. Later on, the formation of hydroxyl radicals was shown in the oxidation of NADPH catalyzed by microsomal NADPH-cytochrome P-450 reductase [9,10]. 

Schnurr et al. [22] showed that rabbit 15-LOX oxidized beef heart submitochondrial particles to form phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids and induced the oxidative modification of membrane proteins. It was also found that the total oxygen uptake significantly exceeded the formation of oxygenated polyenoic acids supposedly due to the formation of hydroxyl radicals by the reaction of ubiquinone with lipid 15-LOX-derived hydroperoxides. However, it is impossible to agree with this proposal because it is known for a long time [23] that quinones cannot catalyze the formation of hydroxyl radicals by the Fenton reaction. Oxidation of intracellular unsaturated acids (for example, linoleic and arachidonic acids) by lipoxygenases can be suppressed by fatty acid binding proteins [24]. 

Excess iron can lead to diabetes mellitus, faulty liver functions, and endocrine disturbance. Iron is a catalyst for oxidative damage leading to lipid peroxidation. The latest hypotheses link peroxidation to heart disease, cancer, and accelerated aging. Iron is involved in the Fenton Reaction, which catalyzes the formation of free radicals that cause excessive damage to cells and their components. 

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