Lipid peroxidation, orlipid oxidation, is a complexchemical process that leads to oxidative degradation oflipids,[1] resulting in the formation ofperoxide andhydroperoxide derivatives.[2] It occurs whenfree radicals, specificallyreactive oxygen species (ROS), interact with lipids withincell membranes, typicallypolyunsaturated fatty acids (PUFAs) as they havecarbon–carbon double bonds. This reaction leads to the formation oflipid radicals, collectively referred to aslipid peroxides orlipid oxidation products (LOPs), which in turn react with otheroxidizing agents, leading to achain reaction that results inoxidative stress andcell damage.
Inpathology andmedicine, lipid peroxidation plays a role in cell damage which has broadly been implicated in thepathogenesis of various diseases and disease states, includingageing,[3][4] whereas infood science lipid peroxidation is one of many pathways torancidity.[5]
Thechemical reaction of lipid peroxidation consists of three phases:initiation,propagation, andtermination.[4]
In theinitiation phase, apro-oxidanthydroxyl radical (OH•)abstracts thehydrogen at theallylic position (–CH2–CH=CH2) ormethine bridge (=CH−)[clarification needed] on the stable lipid substrate, typically apolyunsaturated fatty acid (PUFA), to form the lipid radical (L•) and water (H2O).
In thepropagation phase, the lipid radical (L•) reacts withmolecular oxygen (O2) to form a lipidhydroperoxyl radical (LOO•). The lipid hydroperoxyl radical (LOO•) can further abstract hydrogen from a new PUFA substrate, forming another lipid radical (L•) and now finally a lipidhydroperoxide (LOOH).[6]
The lipid hydroperoxyl radical (LOO•) can also undergo a variety of reactions to produce new radicals.[citation needed]
The additional lipid radical (L•) continues thechain reaction, whilst the lipid hydroperoxide (LOOH) is the primary end product.[6] The formation of lipid radicals is sensitive to thekinetic isotope effect.Reinforced lipids in the membrane can suppress the chain reaction of lipid peroxidation.[7]
Thetermination step can vary, in both its actual chemical reaction and when it will occur.[6] Lipid peroxidation is a self-propagating chain reaction and will proceed until the lipid substrate is consumed and the last two remaining radicals combine, or a reaction which terminates it occurs.[3] Termination can occur when two lipid hydroperoxyl radicals (LOO•) react to formperoxide and oxygen (O2).[3][clarification needed] Termination can also occur when the concentration of radicalspecies is high.[citation needed]
The primary products of lipid peroxidation are lipid hydroperoxides (LOOH).[3]
Whenarachidonic acid is a substrate, isomers ofhydroperoxyeicosatetraenoic acid (HPETEs) andhydroxyeicosatetraenoic acids (HETEs) are formed.[citation needed]
Antioxidants play a crucial role in mitigating lipid peroxidation by neutralizing free radicals, thereby halting radical chain reactions. Key antioxidants includevitamin C andvitamin E.[8] Additionally,enzymes includingsuperoxide dismutase,catalase, andperoxidase contribute to theoxidation response by reducing the presence ofhydrogen peroxide, which is a prevalent precursor of the hydroxyl radical (OH•).
As an example, vitamin E can donate a hydrogen atom to the lipid hydroperoxyl radical (LOO•) to form a vitamin E radical, which further reacts with another lipid hydroperoxyl radical (LOO•) forming non-radical products.[2]
Phototherapy may cause lipid peroxidation, leading to the rupture ofred blood cell cell membranes.[9]
End-products of lipid peroxidation may bemutagenic andcarcinogenic.[10] For instance, the end-productMDA reacts withdeoxyadenosine anddeoxyguanosine in DNA, formingDNA adducts to them, primarilyM1G.[10]
Reactive aldehydes can also formMichael adducts orSchiff bases withthiol oramine groups in amino acid side chains. Thus, they are able to inactivate sensitive proteins through electrophilic stress.[11]
The toxicity of lipid hydroperoxides to animals is best illustrated by the lethal phenotype of glutathione peroxidase 4 (GPX4) knockout mice. These animals do not survive past embryonic day 8, indicating that the removal of lipid hydroperoxides is essential for mammalian life.[12]
It is unclear whether dietary lipid peroxides are bioavailable and play a role in disease, as a healthy human body has protective mechanisms in place against such hazards.[13]
Certain diagnostic tests are available for the quantification of the end-products of lipid peroxidation, to be specific,malondialdehyde (MDA).[10] The most commonly used test is called aTBARS Assay (thiobarbituric acid reactive substances assay). Thiobarbituric acid reacts with malondialdehyde to yield a fluorescent product. However, there are other sources of malondialdehyde, so this test is not completely specific for lipid peroxidation.[14]
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