LIPID PEROXIDATION: HISTORY, MECHANISM, INITIATION, PROPAGATION AND TERMINATION

 HISTORY
The first studies of this lipid oxidation problem was those of the Swiss chemist Nicolas- Theodore de Saussure who observed around 1800 using a simple mercury manometer that a layer of walnut oil exposed to air was able to absorb about 150 times its own volume of oxygen during a one year period.  Parallel with these changes, oil became viscous and had a bad smell. Later, Berzelinus (who discovered selenium) suggested that this oxidation might be involved in the spontaneous ignition of wool lubrified with linseed oil in textile mills. Parmenties A.A, a pharmacist who introduced potato culture in France, hypothesize also that oxygen in combination with fats was the agent of rancidity (Halliwell, 1985).
 

Systematic studies of lipid autoxidation may be considered to have begun around the 40s since Halliwell, (1985) established that hydrocarbon are the primary products of hydrocarbon oxidation. Since the early 1960,s our understanding of the oxidation of unsaturated lipids has advanced considerably as a result of the application of new analytical tools. Detailed studies of the products of polyunsaturated fatty acids were initiated in the 70s by several research groups revealing more complex mixtures than those previously propose (Benzie, 1996).

 With the help of HPLC, several hydro peroxide products could be separated after autoxidation of arachidonic acid (Choo, 2003), including products of lipoxygenase action. The first demonstration of free radical oxidation of membrane phospholipids was green in 1980 (Benzie, 1996), leading to a new fruitful era with a continuous flow of innumerable works devoted to chemistry, biochemistry and medicine.

MECHANISM OF LIPID PEROXIDATION
Lipid peroxidation refers to oxidative degradation of lipids. it is the process whereby free radicals “steal” electrons from the lipids in cell membranes, resulting in cell damage (Benize,1996). This process proceeds by a free radical chain reaction mechanism. Most often, it affects polyunsaturated fatty acids because they contain multiple double bonds in between which the methylene –CH2- groups attach especially the reactive hydrogens. As with any radical reaction, the reaction consists of three major steps; - initiation, propagation and termination.

INITIATION
Initiation is the step whereby a fatty acid radical is produced (Benzie, 1996).  Lipid hydro peroxides are non- radical intermediates derived from unsaturated fatty acids, phospholipids, glycolipids, cholesterol esters and cholesterol itself. There formation occur in enzymatic or non- enzymatic reactions involving activated chemical species known as reactive oxygen species (ROS) which are responsible for toxic effects in the body via various tissue damage (Halliwell, 1985). These ROS include among others hydroxyl radicals, lipid oxyl or peroxyl radicals, singlet oxygen and peroxinitrite form, nitrogen oxide (NO), all these groups of atoms behave as a unit and are now named “free radical” (Choo et al, 2003).

PROPAGATION
        The fatty acid radical is not a very stable molecule, so it reacts readily with molecular oxygen, thereby creating a peroxyl-fatty acid radical. This too is an unstable species that react with another fatty acid producing a different fatty acid radical and a hydrogen peroxide or a cyclic peroxide if it had reacted with itself (Benzie, 1996) this cycle continues as the new fatty acid radical reacts in the same way.

TERMINATION
 When a radical reacts it always produces another radical, which is why the process is called a “chain reaction Mechanism”. The radical reaction stops when two radicals react and produce a non-radical species (Enrique et al, 2007). This happens only when the concentration of radical species is high enough for there to be a high probability of two radicals actually colliding.

Living organisms have evolved different molecules that speed up termination by catching free radicals and therefore protect the cell membrane. One important of such antioxidant is alpha-tocopherol, also known as vitamin E. other antioxidants made within the body include the enzymes super oxide dismutase, catalase and peroxidase (Enrique et al 2007). In conclusion, lipid peroxidation if not terminated fast enough will bring damage to the cell membranes, which consists mainly of lipids (Enrique et al, 2007). In addition, end products of lipid peroxidation may be mutagenic and carcinogenic and phototherapy may cause hemolysis by rupturing red blood cell and cell membranes (Enrique et al, 2007). Certain diagnostic tests are available for the quantification of the end product of lipid peroxidation, specifically malondialdehyde (MDA). The most commonly used test is called a TBARS Assay.
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