Description
The damaging effect of lipid peroxidation arise when free radicals overcome the body’s own protective mechanisms and react with unsaturated fatty acids.
The reaction of polyunsaturated fatty acids (PUFA) with activated oxygen species, results in lipid hydroperoxides (primary lipid peroxidation products) which gives rise to the secondary lipid peroxidation products like alkanes (e.g. ethane and pentane), aliphatic aldehydes (e.g. malondialdehyde [MDA] and 4-hydroxynonenal [HNE]). Primary and secondary lipid peroxidation products act on a variety of molecules that are necessary for correct cell function. Lipid hydroperoxides easily pass the nuclear membrane and can react with nucleic acids. Also, proteins can be attacked on their thiol groups changing their stereochemistry and function. In addition, lipid hydroperoxides interfere with chemical and physical properties of the cell membrane-the fluidity decreases and rigidity increases. The influenced cell membrane cannot maintain its barrier function and there is a loss of intracellular potassium ions as well as intracellular enzymes. If erythrocytes are affected, haemolysis takes place. In this case haemoglobin can initiate or propagate the lipid peroxidation.
Secondary lipid peroxidation products like MDA or HNE can react with DNA as well, especially with the bases guanine and adenine. These DNA abnormalities lead to erroneous transcriptions and as a consequence, altered gene products. Peptide bonds are broken through the impact of MDA in proteins. Aldehydes react with amino groups of proteins building Schiff bases, fundamentally disturbing correct function of proteins. All these toxic features of oxidized fatty acids are discussed in the pathogeneses of many diseases and dysfunction of organs, particularly in arteriosclerosis, tumor diseases, rheumatic diseases and reperfusion damage of organs after ischemic processes.
