Lipid Peroxidation: Definition and Concept
Lipid peroxidation is a process in which reactive oxygen species (ROS) or free radicals attack lipids, particularly the polyunsaturated fatty acids in cell membranes, leading to the formation of peroxides and other damaging by-products. It is a type of oxidative degradation of lipids, primarily affecting the cell membrane's phospholipids. Lipid peroxidation is a key mechanism through which cellular damage occurs, and it plays a significant role in various pathological conditions, including aging, cancer, cardiovascular diseases, and neurodegenerative disorders.
Mechanism of Lipid Peroxidation
The process of lipid peroxidation follows a well-defined chain reaction:
- Initiation: The process begins when a free radical, often a hydroxyl radical (•OH) or a superoxide anion (O2•−), interacts with a polyunsaturated fatty acid in a lipid membrane. This interaction causes the fatty acid’s carbon-hydrogen bond to break, generating a lipid radical (L•).
- Propagation: The lipid radical (L•) formed in the initiation step reacts with molecular oxygen (O2) to produce a lipid peroxyl radical (LOO•). This peroxyl radical can further attack another polyunsaturated fatty acid, continuing the chain reaction and producing more lipid peroxides.
- Termination: The chain reaction can be terminated when two free radicals (such as two lipid peroxyl radicals) react with each other, producing a non-radical, stable product. Antioxidants can also help in terminating the reaction by donating electrons and neutralizing free radicals.
Products of Lipid Peroxidation
Lipid peroxidation generates several by-products, some of which are toxic and contribute to cellular damage:
- Malondialdehyde (MDA): A small, highly reactive compound that is often used as a marker of oxidative stress in the body.
- 4-Hydroxy-2-trans-nonenal (HNE): A highly reactive aldehyde that can covalently modify proteins, DNA, and other macromolecules, leading to cellular dysfunction.
- Isoprostanes: A group of compounds formed from the free radical-induced oxidation of arachidonic acid, which also serve as biomarkers for oxidative stress.
Biological Implications
Lipid peroxidation can lead to the disruption of cell membranes, as the peroxidized lipids compromise the structural integrity and fluidity of the lipid bilayer. The products of lipid peroxidation, like MDA and HNE, can also damage proteins, nucleic acids, and other cellular components, contributing to inflammation, apoptosis, and other forms of cellular injury. This process is associated with a wide range of diseases, including cardiovascular diseases, Alzheimer's disease, and diabetes.
In summary, lipid peroxidation is a critical biochemical process initiated by oxidative stress that leads to cellular damage and has far-reaching implications for health and disease.
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