Fe2 H2O2 Fe3 OH OH

Figure 2-15. Production of the hydroxyl radical via the Fenton reaction.

Because of the reactivity of the hydroxyl radical, and the fact that the ingredients are inexpensive, the Fenton reaction is used on a commercial scale to treat waste water. The Fenton reaction can also occur with copper as the transition metal. Given that Fe2+, Cu+, and H2O2 are abundantly present in biological systems, hydroxyl radicals can be generated via the Fenton reaction in vivo. Reviews by Schutzendubel and Polle (2002) and by Valko et al. (2005) describe the impact of ROS in plants and humans, respectively.

A particularly damaging reaction is the reaction between the hydroxyl radical and unsaturated fatty acid side chains of phospholipids in the cell membrane, a reaction referred to as lipid peroxidation (Figure 2-17).

Figure 2-17. Lipid peroxidation. A hydroxyl radical abstracts a hydrogen from a fatty acid or lipid molecule. After rearrangement to a conjugated structure, the radical reacts with oxygen to form a peroxyl radical. The newly formed peroxyl radical can initiate a chain reaction whereby new peroxyl radicals are formed.

Figure 2-17. Lipid peroxidation. A hydroxyl radical abstracts a hydrogen from a fatty acid or lipid molecule. After rearrangement to a conjugated structure, the radical reacts with oxygen to form a peroxyl radical. The newly formed peroxyl radical can initiate a chain reaction whereby new peroxyl radicals are formed.

The hydroxyl radical will abstract a hydrogen atom from the fatty acid, creating a fatty acid radical with the free electron on a carbon atom in the chain. The radical will typically undergo a rearrangement resulting in a more stable conjugated structure. This newly generated radical can crosslink with a nearby fatty acid radical. Alternatively, the fatty acid radical can react with molecular oxygen to produce a peroxyl radical. This then sets in motion a chain reaction, whereby many new peroxyl radicals are generated. As a consequence of lipid peroxidation, the fluidity of the membrane can be affected, and membrane proteins, especially receptors, can become part of the radical reactions, affecting their function. Ultimately, the membrane can collapse.

More recently, the impact of excess iron on carcinogenesis has been studied. Toyokuni (2002) reported that in kidney cells of rats an overload of iron can result in carcinogenesis because of Fenton-reaction induced damage to a tumor suppressor gene. This is currently an active area of research.

Living organisms have developed various ways to deal with ROS. One mechanism is enzymatic inactivation. The enzyme superoxide dismutase, (E.C. 1.15.1.1) catalyzes the dismutation of superoxide into oxygen (O2) via oxidation, and H2O2 via reduction (see also Section 1.8.2.3). The H2O2, which is reactive itself, is removed through the action of the enzymes catalase (E.C. 1. 11.1.6) and glutathione peroxidase (E.C. 1.11.1.9). Catalase catalyzes the conversion of H2O2 to water and oxygen, whereas glutathione peroxidase catalyzes the formation of oxidized glutathione (G-S-S-G) from reduced glutathione (G-SH), at the expense of H2O2 (Halliwell, 1991).

The other commonly used mechanism to inactivate ROS is through the use of antioxidants. Antioxidants can react with the radical, but rather than turning into another reactive molecule, these compounds are relatively stable in the presence of the radical electron. As a consequence, they scavenge the radical electrons, quench the chain reaction, and avoid further damage. The relative stability of antioxidants containing a radical electron is generally the result of the presence of conjugated bonds, so that the radical electron can be delocalized. As a consequence, aromatic compounds in general, and phenolic compounds in particular are very effective antioxidants. Examples of delocalized radical electrons in phenolic compounds are given in structures 2.11 and 2.38. The antioxidant properties of phenolics will be discussed in more detail in Chapter 7.

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