Lipid peroxidation, free radical initiated propagation

Figure L Free radical initiated propagating of lipid peroxidation. Reproduced with permission from reference 5. Copyright 2000 with lOS Press.

Free radicals are very important both in food systems and in biological systems. In food, the process of lipid auto-oxidation and development of rancidity involves a free radical chain mechanism proceeding via initiation, propagation, and termination steps. This lipid peroxidation process is responsible for the development of off-flavors and undesirable chemical compounds in food. In vivo, free radical-initiated auto-oxidation of cellular membrane lipids can lead to cellular necrosis and is an... 

Fig. 3. Autoxidation of polyunsaturated fatty acids in phospholipid membranes. Addition of oxygen to lipid free radicals is extremely fast. It yields peroxyl radicals ROO which will tend to capture labile hydrogen atoms of neighbouring polyunsaturated lipids. Accidentally produced free radicals will therefore initiate a chain reaction of lipid peroxidation which will propagate along membranes. This process can result in several dozen propagation steps before it is stopped by a termination reaction. Examples of such termination reactions are the recombination of peroxyl radicals and the formation of a stable free radical from a free radical scavenger (scavH). Termination through recombination of low steady-state concentration of alkyl radicals is unlikely in aerobic medium.

Lipid peroxidation is a free radical-mediated, chain reaction resulting in the oxidative deterioration of polyunsaturated fatty acids (PUFAs) defined for this purpose as fatty acids that contain more than two double covalent carbon-carbon bonds. Singlet oxygen can produce lipid hydroperoxides in unsaturated lipids by non-radical processes (Pryor and Castle, 1984), but the reaction usually requires a radical mechanism (Porter, 1984). Polyunsaturated fatty acids are particularly susceptible to attack by free radicals. Lipid peroxidation is a complex process, and three distinct phases are recognized (a) initiation, (b) propagation and (c) termination (see Fig. 2.10). 

The antioxidant radical produced because of donation of a hydrogen atom has a very low reactivity toward the unsaturated lipids or oxygen therefore, the rate of propagation is very slow. The antioxidant radicals are relatively stable so that they do not initiate a chain or free radical propagating autoxidation reaction unless present in very large quantities. These free radical interceptors react with peroxy radicals (ROO ) to stop chain propagation thus, they inhibit the formation of peroxides (Equation 13). Also, the reaction with alkoxy radicals (RO ) decreases the decomposition of hydroperoxides to harmful degradation products (Equation 14). 

To be most effective, primary antioxidants should be added during the induction or initiation stage of the autoxidation reaction cascade. Antioxidants can scavenge the formed free radicals, as the cyclical propagation steps have not occurred at this stage. Addition of primary antioxidants to a lipid that already contains substantial amounts of lipid peroxides may result in loss of antioxidant activity (25). 

Lipid peroxidation can be divided into three separate processes - initiation, propagation, and termination. During initiation a very small number of radicals (e.g., transition metal ions or a radical generated by photolysis or high-energy irradiation) can abstract hydrogen from lipid molecules to yield free radicals of lipids... 

Fig. 4. Mechanism of lipid peroxidation and its inhibition by vitamin E. Lipid peroxidation is initiated by generating a relatively nnreactive carbon-centered radical upon hydrogen abstraction by a hydroxyl radical (1). The fast formation (2) of the more reactive peroxyl radicals (ROO) ensures rapid attack of any peroxidizable substrate either by abstraction of a hydrogen atom (3a) or addition to a double bond (3b). The propagation is teiminated by mutual elimination of peroxyl radicals (4) or by suppression of free-radical formation in the presence of a-tocopherol (a-TOH) (5a). The tocopheryl radical is believed to be neutralized by ascorbic acid (AscAH) (5b) and radical oxygen, and a-tocopherol then re-enters the inhibition cycle.

Lipid peroxidation of biological membranes is a destructive process, proceeding via an autocatalytic chain reaction mechanism [73]. Membrane phospholipids contain hydrogen atoms adjacent to unconjugated olefinic bonds, which make them highly susceptible to free radical oxidation. This is characterised by an initiation step, one or more propagation steps and a termination step [1], which may involve the combination of two radical species or interaction with an antioxidant molecule such as vitamin E. The products formed from such reactions include lipid peroxides, lipid alcohols and aldehydic by-products such as malondialdehyde and 4 hydroxynonenal [73]. 

Chain reactions that form lipid free radicals and lipid peroxides in membranes make a major contribution to ROS-induced injury (Fig. 24.8). An initiator (such as a hydroxyl radical produced locally in the Fenton reaction) begins the chain reaction. It extracts a hydrogen atom, preferably from the double bond of a polyunsaturated fatty acid in a membrane lipid. The chain reaction is propagated when O2 adds to form lipid peroxyl radicals and lipid peroxides. Eventually lipid degradation occurs, forming such products as malondialdehyde (from fatty acids with three or more double bonds), and ethane and pentane (from the w-terminal carbons of 3 and 6 fatty acids, respectively). Malondialdehyde appears in the blood and urine and is used as an indicator of free radical damage. 

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