Lipid alkoxy radical

Figure 17.2 Lipid peroxidation scheme. LH, a polyunsaturated fatty acid LOOM, lipid hydroperoxide LOH, lipid alcohol L, lipid radical LOO, lipid hydroperoxyl radical LO, lipid alkoxyl radical. Initiation the LH hydrogen is abstracted by reactive oxygen (e.g. lipid alkyl radical, lipid alkoxy radical, lipid hydroperoxyl radical, hydroxy radical, etc.) to produce a new lipid alkyl radical, L. Propagation the lipid alkyl, alkoxyl or hydroperoxyl radical abstracts hydrogen from the neighbouring LH to generate a new L radical.

Lipid alkoxy radicals (LO ) decompose in chain scission reaction to a great variety of reactive aldehydes such as malonaldehyde, hydroxyalkenals, 2-alkenals, 2,4-alkadienals and alkanals. Lipid alkoxy radicals also cause the degradation of the apolipoprotein B (apoB) to smaller peptide fragments. 

A synthesis of these results has been presented, and evidence presented for the role of alkoxy radicals generated during lipid oxidation (Bogan and Lamar 1995 Tatarko and Bumpus 1993). 

LOO, the peroxyl radical LH, the lipid substrate L, the lipid-derived alkyl radical AH, a chain-breaking antioxidant A, the antioxidant-derived radical. Copper is the catalyst in this reaction and would also form the alkoxy radical as shown in Reaction 2.9 (see text), which is omitted here for the sake of clarity. 

The most widely used antioxidants are free radical scavengers that remove reactive radicals formed in the initiation and propagation steps of autoxidation. A number of natural or synthetic phenols can compete, even at low concentrations, with lipid molecules as hydrogen donors to hydroperoxy and alkoxy radicals, producing hydroperoxides and alcohols and an unreactive radical. (3-carotene reacts with per-oxy radicals, producing a less-reactive radical. These stabilized radicals do not initiate or propagate the chain reaction. 

Scheme 1. Possible reactions of the autoxidation process. R is an alkyl group of an unsaturated lipid molecule. H is an a-methylenic hydrogen atom easily detachable because of the activating influence of the neighboring double bond or bonds. RO is alkoxy radical, ROO" is peroxy radical, and is an initiator.

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). 

Resting, catalytically inactive, lipoxygenase needs lipid hydroperoxide for activation as was shown with kinetic experiments investigating lipoxygenase [27-31], and are likely to be converted into alkoxy radicals in this process (Scheme 2, step a [24])... 

Lipid derived radicals (L, LO-, and LOO ) are produced during the initiation and propagation stages of the autoxidation of unsaturated lipids. The source of the primary radical in lipid autoxidation is still an open question. However, the reaction may be initiated by cleavage of preformed lipid hydroperoxides (LOOH) by transition metal ions, i ch form lipid alkoxy 1 radicals (LO ), or by metal-catalyzed cleavage ofhydrogen peroxide (HjOj), which forms hydroiQ l radicals ( OH, Fenton... 

Numerous studies have confirmed that lipid hydroperoxides are toxic, their products of decomposition even more so. For example, loss of -OH by cleavage of the relatively weak 0-0 bond gives rise to an alkoxy radical, which may decompose by breaking a neighboring C-C bond (j8-scission), forming an unsaturated aldehyde. 

Reactions of Vitamin E with Lipid Hydroperoxy and Alkoxy Radicals... 

In the presence of traces of transition-metal ions, lipid hydroperoxides are a continuous source for the formation of new alkoxy and peroxy radicals which initiate new chain reactions and therefore act as amplifiers for the initial free radical event. 

In sickle cell membranes, ascorbic acid proved to be an effective antioxidant (Rice-Evans et al. 1986). It is possible that the mechanism of action of ascorbate may involve the scavenging of alkoxy or peroxy radicals by a chain-termination reaction (Halliwell and Gutteridge 1984) or the decreased initiation of lipid peroxidation. 

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